bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer
Authors: Gu Jingtao , Zhang Bo , An Rui , Qian Weikun , Han Liang , Duan Wanxing , Wang Zheng , Ma Qingyong
Published: August 2022

As one of the best-studied long noncoding RNAs, nuclear paraspeckle assembly transcript 1 (NEAT1) plays a pivotal role in the progression of cancers. NEAT1, especially its isoform NEAT1-1, facilitates the growth and metastasis of various cancers, excluding acute promyelocytic leukemia. NEAT1 can be elevated via transcriptional activation or stability alteration in cancers changing the aggressive phenotype of cancer cells. NEAT1 can also be secreted from other cells and be delivered to cancer cells through exosomes. Hence, elucidating the molecular interaction of NEAT1 may shed light on the future treatment of cancer. Herein, we review the molecular function of NEAT1 in cancer progression, and explain how NEAT1 interacts with RNAs, proteins, and DNA promoter regions to upregulate tumorigenic factors.
Targeted Long-Read Bisulfite Sequencing Identifies Differences in the TERT Promoter Methylation Profiles between TERT Wild-Type and TERT Mutant Cancer Cells
Authors: Lee Seungjae , Chang Ti-Cheng , Schreiner Patrick , Fan Yiping , Agarwal Neeraj , Owens Charles , Dummer Reinhard , Kirkwood John M. , Barnhill Raymond L. , Theodorescu Dan , Wu Gang , Bahrami Armita
Published: August 2022

Background: TERT promoter methylation, located several hundred base pairs upstream of the transcriptional start site, is cancer specific and correlates with increased TERT mRNA expression and poorer patient outcome. Promoter methylation, however, is not mutually exclusive to TERT activating genetic alterations, as predicted for functionally redundant mechanisms. To annotate the altered patterns of TERT promoter methylation and their relationship with gene expression, we applied a Pacific Biosciences-based, long-read, bisulfite-sequencing technology and compared the differences in the methylation marks between wild-type and mutant cancers in an allele-specific manner. Results: We cataloged TERT genetic alterations (i.e., promoter point mutations or structural variations), allele-specific promoter methylation patterns, and allele-specific expression levels in a cohort of 54 cancer cell lines. In heterozygous mutant cell lines, the mutant alleles were significantly less methylated than their silent, mutation-free alleles (p < 0.05). In wild-type cell lines, by contrast, both epialleles were equally methylated to high levels at the TERT distal promoter, but differentially methylated in the proximal regions. ChIP analysis showed that epialleles with the hypomethylated proximal and core promoter were enriched in the active histone mark H3K4me2/3, whereas epialleles that were methylated in those regions were enriched in the repressive histone mark H3K27me3. Decitabine therapy induced biallelic expression in the wild-type cancer cells, whereas the mutant cell lines were unaffected. Conclusions: Long-read bisulfite sequencing analysis revealed differences in the methylation profiles and responses to demethylating agents between TERT wild-type and genetically altered cancer cell lines. The causal relation between TERT promoter methylation and gene expression remains to be established.
Recurrent NOMO1 Gene Deletion Is a Potential Clinical Marker in Early-Onset Colorectal Cancer and Is Involved in the Regulation of Cell Migration
Authors: Pérez-García Jésica , Martel-Martel Abel , García-Vallés Paula , Corchete Luis A. , García Juan L. , Gestoso-Uzal Nerea , Vidal-Tocino Rosario , Blanco Óscar , Méndez Lucía , Sánchez-Martín Manuel , Fuentes Manuel , Herrero Ana B. , Holowatyj Andreana N. , Perea José , González-Sarmiento Rogelio
Published: August 2022

The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been progressively increasing over the last decades globally, with causes unexplained. A distinct molecular feature of EOCRC is that compared with cases of late-onset colorectal cancer, in EOCRC cases, there is a higher incidence of Nodal Modulator 1 (NOMO1) somatic deletions. However, the mechanisms of NOMO1 in early-onset colorectal carcinogenesis are currently unknown. In this study, we show that in 30% of EOCRCs with heterozygous deletion of NOMO1, there were pathogenic mutations in this gene, suggesting that NOMO1 can be inactivated by deletion or mutation in EOCRC. To study the role of NOMO1 in EOCRC, CRISPR/cas9 technology was employed to generate NOMO1 knockout HCT-116 (EOCRC) and HS-5 (bone marrow) cell lines. NOMO1 loss in these cell lines did not perturb Nodal pathway signaling nor cell proliferation. Expression microarrays, RNA sequencing, and protein expression analysis by LC–IMS/MS showed that NOMO1 inactivation deregulates other signaling pathways independent of the Nodal pathway, such as epithelial–mesenchymal transition and cell migration. Significantly, NOMO1 loss increased the migration capacity of CRC cells. Additionally, a gut-specific conditional NOMO1 KO mouse model revealed no subsequent tumor development in mice. Overall, these findings suggest that NOMO1 could play a secondary role in early-onset colorectal carcinogenesis because its loss increases the migration capacity of CRC cells. Therefore, further study is warranted to explore other signalling pathways deregulated by NOMO1 loss that may play a significant role in the pathogenesis of the disease.
Predictive Factors of Long-Term Survival after Neoadjuvant Radiotherapy and Chemotherapy in High-Risk Breast Cancer
Authors: Haussmann Jan , Budach Wilfried , Nestle-Krämling Carolin , Wollandt Sylvia , Tamaskovics Balint , Corradini Stefanie , Bölke Edwin , Krug David , Fehm Tanja , Ruckhäberle Eugen , Audretsch Werner , Jazmati Danny , Matuschek Christiane
Published: August 2022

Background: Neoadjuvant radiotherapy (naRT) in addition to neoadjuvant chemotherapy (naCT) has been used for locally advanced, inoperable breast cancer or to allow breast conserving surgery (BCS). Retrospective analyses suggest that naRT + naCT might result in an improvement in pathological complete response (pCR rate and disease-free survival). pCR is a surrogate parameter for improved event-free and overall survival (OS) and allows for the adaption of the post-neoadjuvant therapy regimens. However, it is not clear whether pCR achieved with the addition of naRT has the same prognostic value. Patients and methods: We performed a retrospective re-analysis of 356 patients (cT1-cT4/cN0-N+) treated with naRT and naCT with a long-term follow-up. Patients underwent naRT on the breast and regional lymph nodes combined with a boost to the primary tumor. Chemotherapy with different agents was given either sequentially or concomitantly to naRT. We used the Cox proportional hazard regression model to estimate the effect of pCR in our cohort in different subgroups as well as chemotherapy protocols. Clinical response markers correlating with OS were also analyzed. Results: For patients with median follow-ups of 20 years, 10 years, 15 years, 20 years, and 25 years, OS rates were 69.7%, 60.6%, 53.1%, and 45.1%, respectively. pCR was achieved in 31.1% of patients and associated with a significant improvement in OS (HR = 0.58; CI-95%: 0.41–0.80; p = 0.001). The prognostic impact of pCR was evident across breast cancer subtypes and chemotherapy regimens. Multivariate analysis showed that age, clinical tumor and nodal stage, chemotherapy, and pCR were prognostic for OS. Conclusion: NaCT and naRT prior to surgical resection achieve good long-term survival in high-risk breast cancer. pCR after naRT maintains its prognostic value in breast cancer subtypes and across different subgroups. pCR driven by naRT and naCT independently influences long-term survival.
STEAP1–4 (Six-Transmembrane Epithelial Antigen of the Prostate 1–4) and Their Clinical Implications for Prostate Cancer
Authors: Xu Michael , Evans Latese , Bizzaro Candice L. , Quaglia Fabio , Verrillo Cecilia E. , Li Li , Stieglmaier Julia , Schiewer Matthew J. , Languino Lucia R. , Kelly William K.
Published: August 2022

Six-Transmembrane Epithelial Antigen of the Prostate 1–4 (STEAP1–4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1–4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1–4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1–4 to provide context for past and current efforts to translate STEAP1–4 into the clinic.
Optimal Light Dose for hEGFR-Targeted Near-Infrared Photoimmunotherapy
Authors: Furumoto Hideyuki , Okada Ryuhei , Kato Takuya , Wakiyama Hiroaki , Inagaki Fuyuki , Fukushima Hiroshi , Okuyama Shuhei , Furusawa Aki , Choyke Peter L. , Kobayashi Hisataka
Published: August 2022

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer therapy that targets cancer cells using a monoclonal antibody-photon absorber conjugate (APC) that is bound to the target cell surface. Subsequent application of low levels of NIR light results in immediate cancer cell death. The anti-tumor effect of NIR-PIT in immunocompromised mice depends on immediate cancer cell death; therefore, the efficacy increases in a light-dose-dependent manner. However, NIR-PIT also induces a strong anti-tumor immune activation in immunocompetent mice that begins soon after therapy. Thus, it may be possible to reduce the light dose, which might otherwise cause local edema while maintaining therapeutic efficacy. In this study, we determined the optimal dose of NIR light in NIR-PIT based on a comparison of the therapeutic and adverse effects. Either one of two monoclonal antibodies (mAbs) against human epidermal growth factor receptor (hEGFR), Cetuximab or Panitumumab, were conjugated with a photo-absorbing chemical, IRDye700DX (IR700), and then injected in hEGFR-expressing mEERL (mEERL-hEGFR) tumor-bearing C57BL/6 immunocompetent mice or A431-GFP-luc tumor-bearing athymic immunocompromised mice. NIR light was varied between 0 to 100 J/cm2 one day after administration of APC. In an immunocompromised mouse model, tumor growth was inhibited in a light-dose-dependent manner, yet extensive local edema and weight loss were observed at 100 J/cm2. On the other hand, in an immunocompetent mouse model using the mEERL-hEGFR cell line, maximal tumor response was achieved at 50 J/cm2, with a commensurate decrease in local edema. In this study, we show that a relatively low dose of NIR light is sufficient in an immunocompetent mouse model and avoids side effects seen with higher light doses required in immunocompetent mice. Thus, light dosing can be optimized in NIR-PIT based on the expected immune response.
Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma
Authors: Eichberger Jonas , Weber Florian , Spanier Gerrit , Gerken Michael , Schreml Stephan , Schulz Daniela , Fiedler Mathias , Ludwig Nils , Bauer Richard Josef , Reichert Torsten Eugen , Ettl Tobias
Published: August 2022

Invasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for bone invasion in OSCC. Initially, in silico gene expression analysis was performed for different HNSCC tumor T-stages to find factors associated with invasive (T4a) tumor growth. Afterwards, the protein expression of bone-metabolizing MMP-27, TNFRSF11B (Osteoprotegerin, OPG), and TNFSF11 (RANKL) was investigated via Tissue Microarrays (TMAs) for their impact on mandibular bone invasion. TMAs were assembled from the bone–tumor interface of primary OSCCs of the floor of the mouth and gingiva from 119 patients. Sixty-four carcinomas with patho-histological jaw invasion (pT4a) were compared to 55 carcinomas growing along the mandible without invasion (pT2, pT3). Tissue samples were additionally evaluated for patterns of invasion using the WPOI grading system. Statistical analysis of in silico data revealed decreased MMP-27 mRNA expression to be strongly associated with the pT4a-stage in OSCC, indicating invasive tumor growth with infiltration of adjacent anatomical structures. Our own clinico-pathological data on OSCCs presented a significant decrease of MMP-27 in tumors invading the nearby mandible (pT4a), compared to pT2 and pT3 tumors without bone invasion. Loss of MMP27 evolved as the strongest predictor of mandibular bone invasion in binary logistic regression analysis. To our knowledge, this is the first study investigating the role of MMP-27 expression in OSCC and demonstrating the importance of the loss of MMP-27 in mandibular bone invasion.
Proton Beam Therapy for Esophageal Cancer
Authors: Solidum Jea Giezl N. , Rojo Raniv D. , Wo Jennifer Y. , Dee Edward Christopher
Published: August 2022

Early-stage esophageal cancer is often primarily managed surgically, with the addition of radiotherapy for locally advanced disease. However, current photon-based radiotherapy regimens and surgery results in a high incidence of treatment-related cardiac and pulmonary complications due to the involvement of proximal organs at risk. In addition, the anatomic location of the esophagus raises challenges for radiotherapy due to the anatomical changes associated with diaphragmatic motion, weight loss, tumor changes, and set-up variability. These challenges propelled the interest in proton beam therapy (PBT), which theoretically offers a reduction in the radiation exposure to healthy neighboring tissues with improvements in the therapeutic ratio. Several dosimetric studies support the potential advantages of PBT for esophageal cancer treatment however, translation of these results to improved clinical outcomes remains unclear with limited clinical data, especially in large populations. Studies on the effect on quality of life are likewise lacking. Here, we review the existing and emerging role of PBT for esophageal cancer, including treatment planning, early clinical comparisons of PBT with photon-based techniques, recently concluded and ongoing clinical trials, challenges and toxicities, effects on quality of life, and global inequities in the treatment of esophageal cancer.
Controllable Construction of IrCo Nanoclusters and the Performance for Water Electrolysis
Authors: Mao Fangqin , Zhao Xiaojie , Chang Ying , Jia Jingchun
Published: August 2022

Finding a suitable catalyst is an important research direction in hydrogen (H2) production from water electrolysis. We report a synthetic method to obtain IrxCo/C clusters by polyol reduction. The catalyst is small in size and can be evenly distributed. The Ir3Co/C cluster catalyst had very good activity under acidic conditions. The overpotential of the best-performing Ir3Co/C cluster for the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) is only 290 mV and 91 mV when 10 mA cm−2 and 100 mA cm−2. The catalyst performance may be improved because of the synergistic effect and the small size of the prepared catalyst, which accelerates proton transfer. This approach offers a strategy to reduce costs while improving catalytic activity.
Integrated CO2 Capture and Hydrogenation to Produce Formate in Aqueous Amine Solutions Using Pd-Based Catalyst
Authors: Li Lichun , Chen Xiangcan , Yao Chu , Xu Meng
Published: August 2022

Integrated CO2 capture and hydrogenation to produce formate offers a sustainable approach for reducing carbon dioxide emissions and producing liquid hydrogen carriers (formate) simultaneously. In the current study, three different types of aqueous amine solutions including monoethanolamine (MEA), diethanolamine (DEA) and triethanolamine (TEA) were investigated as CO2-capturing and hydrogenation agents in the presence of a Pd/NAC catalyst. The effect of amine structures on the CO2 absorption products and formate yield was investigated thoroughly. It was found that the formate product was successfully produced in the presence of all three aqueous amine solutions, with tertiary amine TEA accounting for the highest formate yield under the same CO2 loadings. This is due to the fact that primary and secondary amine moieties in MEA and DEA are responsible for the formation of CO2 adducts of carbamate and bicarbonate, whereas the tertiary amine moiety in TEA is responsible for the formation of hydrogenation-favorable bicarbonate as the solo CO2 absorption product. A high yield of formate of 82.6% was achieved when hydrogenating 3 M TEA with 0.3 mol CO2/mol amine solution in the presence of a Pd/NAC catalyst. In addition, the physio-chemical properties of the Pd/NAC catalyst analyzed using TEM, XRD and XPS characterization were applied to rationalize the superior catalytic performance of the catalyst. The reaction mechanism of integrated CO2 capture and hydrogenation to produce formate in aqueous amine solutions over Pd/NAC catalyst was proposed as well.
The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B
Authors: Cornejo Pierre-Jean , Vergoni Bastien , Ohanna Mickaël , Angot Brice , Gonzalez Teresa , Jager Jennifer , Tanti Jean-François , Cormont Mireille
Published: August 2022

Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a as a new mediator of adipocyte insulin resistance. We confirmed the upregulation of miR-34a in adipose tissues of obese mice, which was observed in the adipocyte fraction exclusively. Overexpression of miR-34a in 3T3-L1 adipocytes or in fat pads of lean mice markedly reduced Akt activation by insulin and the insulin-induced glucose transport. This was accompanied by a decreased expression of VAMP2, a target of miR-34a, and an increased expression of the tyrosine phosphatase PTP1B. Importantly, PTP1B silencing prevented the inhibitory effect of miR-34a on insulin signaling. Mechanistically, miR-34a decreased the NAD+ level through inhibition of Naprt and Nampt, resulting in an inhibition of Sirtuin-1, which promoted an upregulation of PTP1B. Furthermore, the mRNA expression of Nampt and Naprt was decreased in adipose tissue of obese mice. Collectively, our results identify miR-34a as a new inhibitor of insulin signaling in adipocytes, providing a potential pathway to target to fight insulin resistance.
2,4-Diacetylphloroglucinol Reduces Beta-Amyloid Production and Secretion by Regulating ADAM10 and Intracellular Trafficking in Cellular and Animal Models of Alzheimer’s Disease
Authors: Jang Bong-Geum , Choi Boyoung , Kim Suyeon , Lee Duk-Shin , Lee Jisun , Koh Young Ho , Jo Sangmee Ahn , Kim Ji-Eun , Kang Tae-Cheon , Kim Min-Ju
Published: August 2022

There is currently no effective treatment against Alzheimer’s disease (AD), although many strategies have been applied to reduce beta-amyloid (Aβ) levels. Here, we investigated 2,4-diacetylphloroglucinol (DAPG) effects on Aβ levels and mechanisms of action. DAPG was the most effective phloroglucinol derivative for reducing Aβ levels, without being toxic, in various models including HEK293 cells overexpressing Swedish mutant amyloid precursor protein (APP) (293sw), primary astrocytes isolated from APPsw/PS1dE9 transgenic mice, and after intrahippocampal injection of DAPG in APPsw/PS1dE9 transgenic mice. DAPG-mediated Aβ reduction was associated with increased soluble APPα (sAPPα) levels mediated by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) but not ADAM17. ADAM10 inhibition in DAPG-treated cells prevented the effects on sAPPα but only partly on intracellular and secreted Aβ. To identify regulators of sAPPα and Aβ secretion, various inhibitors of intracellular trafficking were administered with DAPG. Brefeldin A (BFA) reversed DAPG-mediated changes in Aβ secretion in 293sw cells, whereas golgicide A (GCA) and BFA were effective in primary astrocytes, indicating a cell type-specific regulation of the trafficking. Moreover, GCA or BFA effects on sAPPα, but not Aβ, levels in primary astrocytes resembled those of ADAM10 inhibition, indicating at least partly independent trafficking pathways for sAPPα and Aβ. In conclusion, DAPG might be a promising drug candidate against AD regulating ADAM10 and intracellular trafficking, but optimizing DAPG ability to cross the BBB will be needed.
Abrogation of Cellular Senescence Induced by Temozolomide in Glioblastoma Cells: Search for Senolytics
Authors: Beltzig Lea , Christmann Markus , Kaina Bernd
Published: August 2022

A first-line therapeutic for high-grade glioma, notably glioblastoma (GBM), is the DNA methylating drug temozolomide (TMZ). Previously, we showed that TMZ induces not only apoptosis and autophagy, but also cellular senescence (CSEN). We presented the hypothesis that GBM cells may escape from CSEN, giving rise to recurrent tumors. Furthermore, the inflammatory phenotype associated with CSEN may attenuate chemotherapy and drive tumor progression. Therefore, treatments that specifically target senescent cells, i.e., senolytic drugs, may lead to a better outcome of GBM therapy by preventing recurrences and tumor inflammation. Here, we tested Bcl-2 targeting drugs including ABT-737, ABT-263 (navitoclax), several natural substances such as artesunate, fisetin and curcumin as well as lomustine (CCNU) and ionizing radiation (IR) for their senolytic capacity in GBM cells. Additionally, several proteins involved in the DNA damage response (DDR), ATM, ATR, Chk1/2, p53, p21, NF-kB, Rad51, PARP, IAPs and autophagy, a pathway involved in CSEN induction, were tested for their impact in maintaining CSEN. Treatment of GBM cells with a low dose of TMZ for 8–10 days resulted in >80% CSEN, confirming CSEN to be the major trait induced by TMZ. To identify senolytics, we treated the senescent population with the compounds of interest and found that ABT-737, navitoclax, chloroquine, ATMi, ATRi, BV-6, PX-866 and the natural compounds fisetin and artesunate exhibit senolytic activity, inducing death in senescent cells more efficiently than in proliferating cells. Curcumin showed the opposite effect. No specific effect on CSEN cells was observed by inhibition of Chk1/Chk2, p21, NF-kB, Rad51 and PARP. We conclude that these factors neither play a critical role in maintaining TMZ-induced CSEN nor can their inhibitors be considered as senolytics. Since IR and CCNU did not exhibit senolytic activity, radio- and chemotherapy with alkylating drugs is not designed to eliminate TMZ-induced senescent cancer cells.
Varied Responses to a High m.3243A>G Mutation Load and Respiratory Chain Dysfunction in Patient-Derived Cardiomyocytes
Authors: Ryytty Sanna , Modi Shalem R. , Naumenko Nikolay , Shakirzyanova Anastasia , Rahman Muhammad Obaidur , Vaara Miia , Suomalainen Anu , Tavi Pasi , Hämäläinen Riikka H.
Published: August 2022

The m.3243A>G mutation in mitochondrial tRNA-Leu(UUR) is one of the most common pathogenic mitochondrial DNA mutations in humans. The clinical manifestations are highly heterogenous and the causes for the drastic clinical variability are unknown. Approximately one third of patients suffer from cardiac disease, which often increases mortality. Why only some patients develop cardiomyopathy is unknown. Here, we studied the molecular effects of a high m.3243A>G mutation load on cardiomyocyte functionality, using cells derived from induced pluripotent stem cells (iPSC-CM) of two different m.3243A>G patients, only one of them suffering from severe cardiomyopathy. While high mutation load impaired mitochondrial respiration in both patients’ iPSC-CMs, the downstream consequences varied. mtDNA mutant cells from a patient with no clinical heart disease showed increased glucose metabolism and retained cellular ATP levels, whereas cells from the cardiac disease patient showed reduced ATP levels. In this patient, the mutations also affected intracellular calcium signaling, while this was not true in the other patient’s cells. Our results reflect the clinical variability in mitochondrial disease patients and show that iPSC-CMs retain tissue specific features seen in patients.
How to Verify Non-Presence—The Challenge of Axenic Algae Cultivation
Authors: Pokorny Leo , Hausmann Bela , Pjevac Petra , Schagerl Michael
Published: August 2022

Many phycological applications require the growth and maintenance of pure algae cultures. In some research areas, such as biochemistry and physiology, axenic growth is essential to avoid misinterpretations caused by contaminants. Nonetheless, axenicity—defined as the state of only a single strain being present, free of any other organism—needs to be verified. We compare the available methods to assess axenicity. We first purified unialgal Limnospira fusiformis cultures with an established series of axenicity treatments, and by including two additional treatment steps. The presumable axenic cultures were then tested for their axenic state by applying conventional tests on LB (lysogeny broth) agar-plates, 16S rRNA gene amplicon sequencing, flow-cytometry and epifluorescence microscopy. Only the plate tests indicated axenic conditions. We found a linear relationship between total cell counts of contaminants achieved by flow cytometry and epifluorescence microscopy, with flow cytometry counts being consistently higher. In addition, 16S rRNA gene amplicon sequencing demonstrated its superiority by not only being an efficient tool for axenicity testing, but also for identification of persistent contaminants. Although classic plate tests are still commonly used to verify axenicity, we found the LB-agar-plate technique to be inappropriate. Cultivation-independent methods are highly recommended to test for axenic conditions. A combination of flow-cytometry and 16S rRNA gene amplicon sequencing complement each other and will yield the most reliable result.
Promises and Challenges of Cell-Based Therapies to Promote Lung Regeneration in Idiopathic Pulmonary Fibrosis
Authors: Egea-Zorrilla Alejandro , Vera Laura , Saez Borja , Pardo-Saganta Ana
Published: August 2022

The lung epithelium is constantly exposed to harmful agents present in the air that we breathe making it highly susceptible to damage. However, in instances of injury to the lung, it exhibits a remarkable capacity to regenerate injured tissue thanks to the presence of distinct stem and progenitor cell populations along the airway and alveolar epithelium. Mechanisms of repair are affected in chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), a progressive life-threatening disorder characterized by the loss of alveolar structures, wherein excessive deposition of extracellular matrix components cause the distortion of tissue architecture that limits lung function and impairs tissue repair. Here, we review the most recent findings of a study of epithelial cells with progenitor behavior that contribute to tissue repair as well as the mechanisms involved in mouse and human lung regeneration. In addition, we describe therapeutic strategies to promote or induce lung regeneration and the cell-based strategies tested in clinical trials for the treatment of IPF. Finally, we discuss the challenges, concerns and limitations of applying these therapies of cell transplantation in IPF patients. Further research is still required to develop successful strategies focused on cell-based therapies to promote lung regeneration to restore lung architecture and function.
The Role of SIRT3 in Exercise and Aging
Authors: Zhou Lei , Pinho Ricardo , Gu Yaodong , Radak Zsolt
Published: August 2022

The health benefits of regular exercise are well established. Nonetheless, the molecular mechanism(s) responsible for exercise-induced health benefits remain a topic of debate. One of the key cell-signaling candidates proposed to provide exercise-induced benefits is sirtuin 3 (SIRT3). SIRT3, an NAD+ dependent mitochondrial deacetylase, positively modulates many cellular processes, including energy metabolism, mitochondrial biogenesis, and protection against oxidative stress. Although the exercise-induced change in SIRT3 signaling is a potential mechanism contributing to the health advantages of exercise on aging, studies investigating the impact of exercise on SIRT3 abundance in cells provide conflicting results. To resolve this conundrum, this narrative review provides a detailed analysis of the role that exercise-induced changes in SIRT3 play in providing the health and aging benefits associated with regular physical activity. We begin with an overview of SIRT3 function in cells followed by a comprehensive review of the impact of exercise on SIRT3 expression in humans and other mammalians. We then discuss the impact of SIRT3 on aging, followed by a thorough analysis of the cell-signaling links between SIRT3 and exercise-induced adaptation. Notably, to stimulate future research, we conclude with a discussion of key unanswered questions related to exercise, aging, and SIRT3 expression.
Glycosylation in Renal Cell Carcinoma: Mechanisms and Clinical Implications
Authors: Zhu Xinqing , Al-Danakh Abdullah , Zhang Lin , Sun Xiaoxin , Jian Yuli , Wu Haotian , Feng Dan , Wang Shujing , Yang Deyong
Published: August 2022

Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system, accounting for around 2% of all cancer diagnoses and deaths worldwide. Clear cell RCC (ccRCC) is the most prevalent and aggressive histology with an unfavorable prognosis and inadequate treatment. Patients’ progression-free survival is considerably improved by surgery; however, 30% of patients develop metastases following surgery. Identifying novel targets and molecular markers for RCC prognostic detection is crucial for more accurate clinical diagnosis and therapy. Glycosylation is a critical post-translational modification (PMT) for cancer cell growth, migration, and invasion, involving the transfer of glycosyl moieties to specific amino acid residues in proteins to form glycosidic bonds through the activity of glycosyltransferases. Most cancers, including RCC, undergo glycosylation changes such as branching, sialylation, and fucosylation. In this review, we discuss the latest findings on the significance of aberrant glycans in the initiation, development, and progression of RCC. The potential biomarkers of altered glycans for the diagnosis and their implications in RCC have been further highlighted.
SALL4: An Intriguing Therapeutic Target in Cancer Treatment
Authors: Moein Shiva , Tenen Daniel G. , Amabile Giovanni , Chai Li
Published: August 2022

Spalt-Like Transcription Factor 4 (SALL4) is a critical factor for self-renewal ability and pluripotency of stem cells. On the other hand, various reports show tight relation of SALL4 to cancer occurrence and metastasis. SALL4 exerts its effects not only by inducing gene expression but also repressing a large cluster of genes through interaction with various epigenetic modifiers. Due to high expression of SALL4 in cancer cells and its silence in almost all adult tissues, it is an ideal target for cancer therapy. However, targeting SALL4 meets various challenges. SALL4 is a transcription factor and designing appropriate drug to inhibit this intra-nucleus component is challenging. On the other hand, due to lack of our knowledge on structure of the protein and the suitable active sites, it becomes more difficult to reach the appropriate drugs against SALL4. In this review, we have focused on approaches applied yet to target this oncogene and discuss the potential of degrader systems as new therapeutics to target oncogenes.
Optical Monitoring in Neonatal Seizures
Authors: Howard Rachel , Li Runci , Harvey-Jones Kelly , Verma Vinita , Lange Frédéric , Boylan Geraldine , Tachtsidis Ilias , Mitra Subhabrata
Published: August 2022

Background: Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics. Aim: To perform a systematic review of optical biomarkers to identify changes in cerebral haemodynamics and metabolism during the pre-ictal, ictal, and post-ictal phases of neonatal seizures. Method: A systematic search was performed in eight databases. The search combined the three broad categories: (neonates) AND (NIRS) AND (seizures) using the stepwise approach following PRISMA guidance. Results: Fifteen papers described the haemodynamic and/or metabolic changes observed with NIRS during neonatal seizures. No randomised controlled trials were identified during the search. Studies reported various changes occurring in the pre-ictal, ictal, and post-ictal phases of seizures. Conclusion: Clear changes in cerebral haemodynamics and metabolism were noted during the pre-ictal, ictal, and post-ictal phases of seizures in neonates. Further studies are necessary to determine whether NIRS-based methods can be used at the cot-side to provide clear pathophysiological data in real-time during neonatal seizures.
Correction: Lee et al. Protein Arginine Methyltransferases in Neuromuscular Function and Diseases. Cells 2022, 11, 364
Authors: Lee Jinwoo , An Subin , Lee Sang-Jin , Kang Jong-Sun
Published: August 2022

The authors wish to make the following corrections to this paper [...]
Effects of the Processing Technology of CVD-ZnSe, Cr2+:ZnSe, and Fe2+:ZnSe Polycrystalline Optical Elements on the Damage Threshold Induced by a Repetitively Pulsed Laser at 2.1 µm
Authors: Yudin Nikolay , Antipov Oleg , Balabanov Stanislav , Eranov Ilya , Getmanovskiy Yuri , Slyunko Elena
Published: August 2022

Polycrystalline zinc selenide (ZnSe) and Cr2+ or Fe2+ doped ZnSe are key optical elements in mid-infrared laser systems. The laser-induced damage of the optical elements is the limiting factor for increasing the power and pulse energy of the lasers. In the present work, the optical damage of the ZnSe, Cr2+:ZnSe, and Fe2+:ZnSe samples induced by a repetitively pulsed Ho3+:YAG laser at 2091 nm was studied. The probability of the optical damage and the laser-induced damage threshold (LIDT) were determined for the samples manufactured using different processing techniques. The highest LIDT was found in ZnSe samples annealed in an argon atmosphere. It was also found that the samples annealed in a zinc atmosphere or with hot isostatic pressing resulted in a decrease in the LIDT. The Cr2+-doped ZnSe had the lowest LIDT at 2.1 µm compared to Fe2+-doped or undoped ZnSe. The LIDT fluence of all tested ZnSe samples decreased with the increase in the pulse repetition rate and the exposure duration. The results obtained may be used to improve the treatment procedures of ZnSe, Cr2+:ZnSe, and Fe2+:ZnSe polycrystals to further increase their LIDT.
Manufacturing and Thermal Shock Characterization of Porous Yttria Stabilized Zirconia for Hydrogen Energy Systems
Authors: Riyad M. Faisal , Mahmoudi Mohammadreza , Minary-Jolandan Majid
Published: August 2022

Porous yttriastabilized zirconia (YSZ), in a composite with NiO, is widely used as a cermet electrode in solid oxide fuel cells (SOFCs) and solid oxide electrolysis cells (SOECs). Given cycles of high temperature in these energy devices, mechanical integrity of the porous YSZ is critical. Pore morphology, as well as properties of the ceramic, ultimately affect the mechanical properties of the cermet electrode. Here, we fabricated porous YSZ sheets via freezing of an aqueous slurry on a cold thermoelectric plate and quantified their flexural properties, both for as-fabricated samples and samples subjected to thermal shock at 200 °C to 500 °C. Results of this work have implications for the hydrogen economy and global decarbonization efforts, in particular for the manufacturing of SOFCs and SOECs.
The Study of Nutrient Intake and Adolescent Girls’ Quality of Life in a Rural Area of Indonesia
Authors: Sari Puspa , Herawati Dewi Marhaeni Diah , Dhamayanti Meita , Hilmanto Dany
Published: August 2022

An inadequate nutrient intake correlates with malnutrition, a problem affecting many adolescents worldwide. Nutrient intake is associated with quality of life (QoL). Our study analyzed the relationship between nutrient intake and adolescents’ QoL. We conducted a cross-sectional study. Through simple random sampling, 157 adolescent girls were selected. Nutrition status was assessed using anthropometric measurements. Nutrient intake was collected using the food frequency questionnaire (FFQ). WHOQOL BREF was used to explore adolescent girls’ quality of life. The median of nutrient intake: energy (908.25 kcal); protein (24.16 g); carbohydrate (128.89 g); fat (21.89 g); vitamin A (77.10 mg); vitamin E (1.40 mg); vitamin B1 (0.19 mg); vitamin B2 (0.29 mg); vitamin B6 (0.45 mg); folic acid (35.13 mg); vitamin C (12.60 mg); calcium (197.46 mg); magnesium (93.72 mg); iron (2.64 mg); and zinc (2.09 mg). The adolescents’ QoL scores were physical health 44 (25–81), psychological domain 56 (19–94), social relationships 56 (19–94), and environmental domain 56 (31–100). The strongest correlations were between (1) physical health with carbohydrates, vitamin C, and fat; (2) psychological domain with calcium; (3) social relationships with carbohydrates and vitamin C; and (4) environmental domain with BMI and zinc. There was a significant positive correlation between the intake of some nutrients and adolescents’ QoL, despite the observation of some significant negative correlations. The findings of this study indicate that more attention should be focused on adolescents’ nutrient intake in order to improve their QoL.
Food Insecurity among Low-Income Households with Children Participating in a School-Based Fruit and Vegetable Co-Op
Authors: Marshall Allison N. , Chuang Ru-Jye , Chow Joanne , Ranjit Nalini , Dave Jayna M. , Mathur Mallika , Markham Christine , Sharma Shreela V.
Published: August 2022

The purpose of this study was to evaluate the impact of a nutrition intervention on food insecurity among low-income households with children. Data were collected from 371 parent–child dyads in a quasi-experimental evaluation study of a 1-year intervention (n = 6 intervention schools receiving Brighter Bites, n = 6 wait-list control schools), and longitudinal follow-up of the intervention group 2 years post-intervention in Houston, Texas. Data were collected at three timepoints: at baseline and 1 year for all participants, and at 2 year follow-up for the intervention group (the wait-list control group received the intervention during that time). At baseline, most parents reported food insecurity (60.6%; 70% intervention group, 53.6% control). Food insecurity decreased significantly from 81.3% to 61.7% [(−0.32, −0.07) p = 0.002] among intervention participants immediately post-intervention. After adjusting for ethnicity, 2 years post-intervention the predicted percentage of participants reporting food insecurity decreased significantly by roughly 35.4% from 76.4% at baseline to 41.0% [(−0.49, −0.22), p < 0.001]. Between-group changes were not significant. The re-sults of this study demonstrated a significant positive impact of Brighter Bites on food security in the short and long-term among low-income households with children, albeit results should be in-terpreted with caution.
Ovarian Tissue Cryopreservation in Children and Adolescents
Authors: Arapaki Angeliki , Christopoulos Panagiotis , Kalampokas Emmanouil , Triantafyllidou Olga , Matsas Alkis , Vlahos Nikolaos F.
Published: August 2022

Cancer during childhood and adolescence remains a major public health issue, affecting a significant portion of this age group. Although newer anti-cancer treatments have improved survival rates, this comes at a cost in terms of gonadotoxic effects. As a result, the preservation of fertility is important. Ovarian tissue cryopreservation, one of the newest methods, has some advantages, especially for prepubertal patients: no need for ovarian stimulation, thus, no further risk for estrogen-sensitive cancer types, and preservation of more and better-quality primordial follicles of the ovarian cortex. The most frequent indications include treatment with alkylating agents, ovarian-focused radiotherapy, leukemias, lymphomas, brain and neurological tumors, as well as Turner syndrome and benign hemoglobinopathies. An expected survival exceeding 5 years, the absence of systematic disease and an overall risk of premature ovarian insufficiency over 50% are among the criteria that need to be fulfilled in order for a patient to undertake this method. Orthotopic transplantation is more frequently used, since it can allow both live birth and the recovery of endocrine function. Reimplantation of malignant cells is always a major risk and should always be taken into consideration. Histological analysis, as well as immunohistochemical and molecular methods, are needed in order to improve the search for malignant cells before transplantation. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications and risks which can be an important tool in terms of preserving fertility in younger women.
The Effect of Parental Beliefs on Post-Traumatic Symptoms of the Parent and Child after the Child’s Surgery
Authors: Ben-Ari Amichai , Ankri Yael L. E. , Aloni Roy , Buniak-Rojas Orly
Published: August 2022

In recent years, many studies have attempted to find the main predictors of the development of post-traumatic symptoms in children following medical procedures. Recent studies found a link between parental beliefs and children’s post-traumatic symptoms in various medical contexts such as life-threatening illness, pain, and hospitalization. This study aims to examine the relationship between parental beleifs and post-traumatic symptoms in children and parents after surgical interventions of the children. The study was conducted among 149 children who underwent surgery and their parents. The children and parents were examined at 2 time points- during hospitalization, and 4 months after the hospitalization. Questionnaires were administered measuring parental beleifs pertaining to parental distress, and post-traumatic symptoms among children. results show a correlation between the factors. In addition, it was found that the parents’ distress is a mediating relationship between the parents’ perceptions and the child’s level of distress. It has been found that there is a link between some of the parental beleifs and parental stress symptoms and post-traumatic symptoms in the children. Parental beliefs that were found to influence these variables were related to parental beliefs regarding children’s suffering and pain during surgery. In addition, children of parents with higher levels of religious and spiritual beliefs were found to have fewer post-traumatic symptoms. This study sheds light on parental beliefs that may have the power to influence parental stress levels and children’s post-traumatic symptoms after surgery.
The Leucocyte Telomere Length, GSTM1 and GSTT1 Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease
Authors: Tacheva Tanya , Zienolddiny-Narui Shanbeh , Dimov Dimo , Vlaykova Denitsa , Miteva Iva , Vlaykova Tatyana
Published: August 2022

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidative stress both in the airways and blood and other organs. Elevated oxidative stress and inflammation have been reported to affect leucocyte telomere length (LTL). Glutathione S-transferase (GST) enzymes are a large family of xenobiotic-metabolizing enzymes that utilize different ROS products. We aimed to explore the link between GSTM1 and GSTT1 gene polymorphisms, LTL and COPD risk. For GSTM1, we genotyped 152 COPD patients and 131 non-affected controls; for GSTT1, we genotyped 149 COPD patients and 130 controls. We were able to assess TL for 91 patients and 88 controls. There was a significant difference in the GSTM1 null genotype frequency between the patients and controls (0.59 vs. 0.38, p ≤ 0.000), but such was not found for GSTT1 (p = 0.192). When combining both polymorphisms, we obtained a significantly greater presence of at least one null genotype among patients (0.12 vs. 0.05, p = 0.027). An association between GSTT1 and LTL was not found. COPD patients carrying the GSTM1 null genotype had shorter telomeres compared to those carrying the non-null genotype (15,720 bp vs. 22,442 bp, p = 0.008); as for the controls, it was the opposite (31,354 bp vs. 17,800 bp, p = 0.020). The significance in both groups remained when combining GSTM1 and GSTT1 (COPD (at least one null) 16,409 bp vs. COPD (non-null) 22,092 bp, p = 0.029; control (at least one null) 29,666 bp vs. control (non-null) 16,370 bp, p = 0.027). The total glutathione level in GSTM1 non-null controls was higher compared to the null genotype (15.39 ng/mL vs. 5.53 ng/mL, p = 0.002). In COPD patients, we found no association (p = 0.301). In conclusion, according to our results, GSTM1, but not GSTT1, null genotypes might play a role in leucocyte telomere shortening, and thus be involved in the pathogenesis of COPD.
Vertical Growth Dynamics and Multifractality of the Surface of Electropolymerized Poly(o-ethoxyaniline) Thin Films
Authors: de Souza Cindel , Gandarilla Ariamna , Brito Walter , Sanches Edgar , Das Abhijeet , Kumar Sanjeev , Matos Robert , Ţălu Ştefan , da Fonseca Filho Henrique
Published: August 2022

Electropolymerized poly(o-ethoxyaniline) (POEA) nanostructured thin films were successfully deposited on indium tin oxide (ITO) substrate. The surface dynamic of the films was extensively investigated using morphological and multifractal parameters extracted from the atomic force microscopy (AFM). AFM topographical maps reveal surfaces with different morphologies as a function of the deposition cycles. The height parameters show that there is greater spatial vertical growth for films deposited with higher cycles of deposition. After five cycles of deposition occurs the formation of a more isotropic surface, while for 15 cycles a less isotropic surface is observed. The Minkowski functionals confirm that morphological aspects of the two films change according to the amount of deposition cycles employed. The POEA surfaces also exhibit a strong multifractal nature with a decrease in the multifractal spectrum width as the number of deposition cycles increases. Our findings prove that deposition cycles can be useful in controlling the vertical growth and surface dynamics of electropolymerized POEA nanostructured samples, which can be useful for improving the fabrication of POEA-coated ITO-based devices.