bluuebunny/crossref_metadata_2025 huggingface dataset:
Type II Collagen-Conjugated Mesenchymal Stem Cells Micromass for Articular Tissue Targeting
Authors: Sulaiman Shamsul Bin , Chowdhury Shiplu Roy , Busra Mohd Fauzi Bin Mh , Abdul Rani Rizal Bin , Mohamad Yahaya Nor Hamdan Bin , Tabata Yasuhiko , Hiraoka Yosuke , Haji Idrus Ruszymah Binti , Hwei Ng Min
Published: July 2021

The tissue engineering approach in osteoarthritic cell therapy often requires the delivery of a substantially high cell number due to the low engraftment efficiency as a result of low affinity binding of implanted cells to the targeted tissue. A modification towards the cell membrane that provides specific epitope for antibody binding to a target tissue may be a plausible solution to increase engraftment. In this study, we intercalated palmitated protein G (PPG) with mesenchymal stem cells (MSCs) and antibody, and evaluated their effects on the properties of MSCs either in monolayer state or in a 3D culture state (gelatin microsphere, GM). Bone marrow MSCs were intercalated with PPG (PPG-MSCs), followed by coating with type II collagen antibody (PPG-MSC-Ab). The effect of PPG and antibody conjugation on the MSC proliferation and multilineage differentiation capabilities both in monolayer and GM cultures was evaluated. PPG did not affect MSC proliferation and differentiation either in monolayer or 3D culture. The PPG-MSCs were successfully conjugated with the type II collagen antibody. Both PPG-MSCs with and without antibody conjugation did not alter MSC proliferation, stemness, and the collagen, aggrecan, and sGAG expression profiles. Assessment of the osteochondral defect explant revealed that the PPG-MSC-Ab micromass was able to attach within 48 h onto the osteochondral surface. Antibody-conjugated MSCs in GM culture is a potential method for targeted delivery of MSCs in future therapy of cartilage defects and osteoarthritis.
Ruxolitinib Combined with Gemcitabine against Cholangiocarcinoma Growth via the JAK2/STAT1/3/ALDH1A3 Pathway
Authors: Chung Shin-Yi , Hung Yi-Ping , Pan Yi-Ru , Chang Yu-Chan , Wu Chiao-En , Hsu Dennis Shin-Shian , Chang Peter Mu-Hsin , Lu Meng-Lun , Huang Chi-Ying F. , Su Yeu , Hsiao Michael , Yeh Chun-Nan , Chen Ming-Huang
Published: July 2021

Cholangiocarcinoma is the most common primary malignant tumor of the bile duct. The current standard first-line treatment for advanced or metastatic cholangiocarcinoma is gemcitabine and cisplatin. However, few effective treatment choices exist for refractory cholangiocarcinoma, and additional therapeutic drugs are urgently required. Our previous work demonstrated that the ALDH isoform 1A3 plays a vital role in the malignant behavior of cholangiocarcinoma and may serve as a new therapeutic target. In this study, we found a positive correlation between ALDH1A3 protein expression levels and the cell migration abilities of three cholangiocarcinoma cell lines, which was verified using ALDH1A3-overexpressing and ALDH1A3-knockdown clones. We also used ALDH1A3-high and ALDH1A3-low populations of cholangiocarcinoma cell lines from the library of integrated network-based cellular signatures (LINCS) program and assessed the effects of ruxolitinib, a commercially available JAK2 inhibitor. Ruxolitinib had a higher cytotoxic effect when combined with gemcitabine. Furthermore, the nuclear translocation STAT1 and STAT3 heterodimers were markedly diminished by ruxolitinib treatment, possibly resulting in decreased ALDH1A3 activation. Notably, ruxolitinib alone or combined with gemcitabine led to significantly reduced tumor size and weight. Collectively, our studies suggest that ruxolitinib might suppress the ALDH1A3 activation through the JAK2/STAT1/3 pathway in cholangiocarcinoma, and trials should be undertaken to evaluate its efficacy in clinical therapy.
Pharmacologically Inhibiting Glycogen Synthase Kinase-3β Ameliorates Renal Inflammation and Nephrotoxicity in an Animal Model of Cisplatin-Induced Acute Kidney Injury
Authors: Hsing Chung-Hsi , Tsai Cheng-Chieh , Chen Chia-Ling , Lin Yu-Hui , Tseng Po-Chun , Satria Rahmat Dani , Lin Chiou-Feng
Published: July 2021

The adverse effect of cisplatin administration causes acute kidney injury (AKI) following renal inflammation and nephrotoxicity, characterized by proximal tubular cell apoptosis and necrosis. Pro-apoptotic and pro-inflammatory roles of glycogen synthase kinase (GSK)-3β have been reported. This study investigated the therapeutic blockade of GSK-3β in cisplatin-induced AKI. A renal cisplatin nephrotoxicity model showed activation of GSK-3β in vivo, particularly in proximal tubular epithelial cells. Pharmacologically inhibiting GSK-3β abolished cisplatin nephrotoxicity, including proximal tubular injury, cell cytotoxicity, and biochemical dysfunction. Additionally, GSK-3β inhibitor treatment ameliorated renal inflammation by reducing immune cell infiltration, cell adhesion molecule expression, and pro-inflammatory cytokine/chemokine production. Cisplatin treatment caused GSK-3β activation in vitro in the human renal proximal tubular epithelial cell line HK-2, whereas either pharmacological administration of GSK-3β inhibitors or genetic transduction of GSK-3β short-hairpin RNA impeded cisplatin-induced cytotoxicity. These results indicate that cisplatin activates GSK-3β followed by GSK-3β-mediated renal inflammation and nephrotoxicity, contributing to AKI.
Addition of V-Stage to Conventional TNM Staging to Create the TNVM Staging System for Accurate Prediction of Prognosis in Colon Cancer: A Multi-Institutional Retrospective Cohort Study
Authors: Bae Jung Hoon , Kim Ji Hoon , Lee Jaeim , Kye Bong-Hyeon , Lee Sang Chul , Lee In Kyu , Kang Won Kyung , Cho Hyeon-Min , Lee Yoon Suk
Published: July 2021

We evaluated the prognostic impact of vascular invasion (VI) compared with nodal (N) stage and developed a new staging system including VI in colon cancer. Patients who underwent curative resection with stage II-III colon cancer were assigned to VI and non-VI groups; the latter was subclassified as N0, N1, and N2; a new TNVM staging was devised by adding the V-stage. Among the 2243 study participants, the VI group independently showed worse oncological outcomes than the N1 group (disease-free survival (DFS), hazard-ratio (HR) 1.704, 1.267–2.291; overall survival (OS), HR 2.301, 1.582–3.348). The 5-year DFS in the VI group was 63.4% [N1b (74.6%), p = 0.003; N2a (69.7%), p = 0.126; and N2b (56.8%), p = 0.276], and the 5-year OS was 76.6% [N1b (84.9%), p = 0.004; N2a (83.0%), p = 0.047; and N2b (76.1%), p = 0.906]. Thus, we considered VI as N2a in TNVM staging; 78 patients (3.5%) underwent upstaging. The 5-year OS rates of stage IIB and IIC increased from 88.6% and 65.9% in TNM staging to 90.5% and 85.7% in TNVM staging, respectively. In stage II–III colon cancer, VI had a similar prognostic impact as the N2 stage without VI. The incorporation of the V-stage into the conventional TNM staging facilitates better prediction of prognosis.
NF-κB and Human Cancer: What Have We Learned over the Past 35 Years?
Authors: Gilmore Thomas D.
Published: July 2021

Transcription factor NF-κB has been extensively studied for its varied roles in cancer development since its initial characterization as a potent retroviral oncogene. It is now clear that NF-κB also plays a major role in a large variety of human cancers, including especially ones of immune cell origin. NF-κB is generally constitutively or aberrantly activated in human cancers where it is involved. These activations can occur due to mutations in the NF-κB transcription factors themselves, in upstream regulators of NF-κB, or in pathways that impact NF-κB. In addition, NF-κB can be activated by tumor-assisting processes such as inflammation, stromal effects, and genetic or epigenetic changes in chromatin. Aberrant NF-κB activity can affect many tumor-associated processes, including cell survival, cell cycle progression, inflammation, metastasis, angiogenesis, and regulatory T cell function. As such, inhibition of NF-κB has often been investigated as an anticancer strategy. Nevertheless, with a few exceptions, NF-κB inhibition has had limited success in human cancer treatment. This review covers general themes that have emerged regarding the biological roles and mechanisms by which NF-κB contributes to human cancers and new thoughts on how NF-κB may be targeted for cancer prognosis or therapy.
HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer
Authors: Sekino Yohei , Pham Quoc Thang , Kobatake Kohei , Kitano Hiroyuki , Ikeda Kenichiro , Goto Keisuke , Inoue Shogo , Hayashi Tetsutaro , Shiota Masaki , Yasui Wataru , Teishima Jun
Published: July 2021

Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and function of HOXB5 and involvement of HOXB5 in neuroendocrine differentiation in PCa. Immunohistochemistry showed that 56 (43.8%) of 128 cases of localized PCa were positive for HOXB5. HOXB5-positive cases were associated with poor prostate-specific antigen recurrence-free survival after prostatectomy. Among 74 cases of metastatic PCa, 43 (58.1%) were positive for HOXB5. HOXB5 expression was higher in metastatic PCa than that in localized PCa. HOXB5 knockdown suppressed cell growth and invasion, but HOXB5 overexpression increased cell growth and invasion in PCa cell lines. Furthermore, HOXB5 regulated RET expression. Gene set enrichment analysis revealed that Nelson androgen response gene set was enriched in low HOXB5 expression group. RB1 knockout increased HOXB5 expression. Of note, additional p53 knockdown further increased HOXB5 expression in RB1 knockout cells. In silico analysis showed that HOXB5 expression was increased in neuroendocrine PCa (NEPC). These results suggest that HOXB5 may be a promising prognostic marker after prostatectomy and is involved in progression to NEPC.
Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context
Authors: Ershov Pavel , Kaluzhskiy Leonid , Mezentsev Yuri , Yablokov Evgeniy , Gnedenko Oksana , Ivanov Alexis
Published: July 2021

A global protein interactome ensures the maintenance of regulatory, signaling and structural processes in cells, but at the same time, aberrations in the repertoire of protein–protein interactions usually cause a disease onset. Many metabolic enzymes catalyze multistage transformation of cholesterol precursors in the cholesterol biosynthesis pathway. Cancer-associated deregulation of these enzymes through various molecular mechanisms results in pathological cholesterol accumulation (its precursors) which can be disease risk factors. This work is aimed at systematization and bioinformatic analysis of the available interactomics data on seventeen enzymes in the cholesterol pathway, encoded by HMGCR, MVK, PMVK, MVD, FDPS, FDFT1, SQLE, LSS, DHCR24, CYP51A1, TM7SF2, MSMO1, NSDHL, HSD17B7, EBP, SC5D, DHCR7 genes. The spectrum of 165 unique and 21 common protein partners that physically interact with target enzymes was selected from several interatomic resources. Among them there were 47 modifying proteins from different protein kinases/phosphatases and ubiquitin-protein ligases/deubiquitinases families. A literature search, enrichment and gene co-expression analysis showed that about a quarter of the identified protein partners was associated with cancer hallmarks and over-represented in cancer pathways. Our results allow to update the current fundamental view on protein–protein interactions and regulatory aspects of the cholesterol synthesis enzymes and annotate of their sub-interactomes in term of possible involvement in cancers that will contribute to prioritization of protein targets for future drug development.
Bioelectromagnetic Platform for Cell, Tissue, and In Vivo Stimulation
Authors: Ashbaugh Ryan C. , Udpa Lalita , Israeli Ron R. , Gilad Assaf A. , Pelled Galit
Published: July 2021

Magnetogenetics is a new field that utilizes electromagnetic fields to remotely control cellular activity. In addition to the development of the biological genetic tools, this approach requires designing hardware with a specific set of demands for the electromagnets used to provide the desired stimulation for electrophysiology and imaging experiments. Here, we present a universal stimulus delivery system comprising four magnet designs compatible with electrophysiology, fluorescence and luminescence imaging, microscopy, and freely behaving animal experiments. The overall system includes a low-cost stimulation controller that enables rapid switching between active and sham stimulation trials as well as precise control of stimulation delivery thereby enabling repeatable and reproducible measurements.
A Preliminary Exploration of Pitch Discrimination, Temporal Sequencing, and Prosodic Awareness Skills of Children Who Participate in Different School-Based Music Curricula
Authors: Flagge Ashley G. , Neeley Mary Ellen , Davis Tara M. , Henbest Victoria S.
Published: July 2021

Musical training has been shown to have a positive influence on a variety of skills, including auditory-based tasks and nonmusical cognitive and executive functioning tasks; however, because previous investigations have yielded mixed results regarding the relationship between musical training and these skills, the purpose of this study was to examine and compare the auditory processing skills of children who receive focused, daily musical training with those with more limited, generalized musical training. Sixteen typically developing children (second–fourth grade) from two different schools receiving different music curricula were assessed on measures of pitch discrimination, temporal sequencing, and prosodic awareness. The results indicated significantly better scores in pitch discrimination abilities for the children receiving daily, focused musical training (School 1) compared to students attending music class only once per week, utilizing a more generalized elementary school music curriculum (School 2). The findings suggest that more in-depth and frequent musical training may be associated with better pitch discrimination abilities in children. This finding is important given that the ability to discriminate pitch has been linked to improved phonological processing skills, an important skill for developing spoken language and literacy. Future investigations are needed to determine whether the null findings for temporal sequencing and prosodic awareness can be replicated or may be different for various grades and tasks for measuring these abilities.
Brain Regions Involved in Underlying Syntactic Processing of Mandarin Chinese Intransitive Verbs: An fMRI Study
Authors: Wang Xin , Feng Shiwen , Zhou Tongquan , Wang Renyu , Wu Guowei , Ni Fengshan , Yang Yiming
Published: July 2021

According to the Unaccusative Hypothesis, intransitive verbs are divided into unaccusative and unergative ones based on the distinction of their syntactic properties, which has been proved by previous theoretical and empirical evidence. However, debate has been raised regarding whether intransitive verbs in Mandarin Chinese can be split into unaccusative and unergative ones syntactically. To analyze this theoretical controversy, the present study employed functional magnetic resonance imaging to compare the neural processing of deep unaccusative, unergative sentences, and passive sentences (derived structures undergoing a syntactic movement) in Mandarin Chinese. The results revealed no significant difference in the neural processing of deep unaccusative and unergative sentences, and the comparisons between passive sentences and the other sentence types revealed activation in the left superior temporal gyrus (LSTG) and the left middle frontal gyrus (LMFG). These findings indicate that the syntactic processing of unaccusative and unergative verbs in Mandarin Chinese is highly similar but different from that of passive verbs, which suggests that deep unaccusative and unergative sentences in Mandarin Chinese are both base-generated structures and that there is no syntactic distinction between unaccusative and unergative verbs in Mandarin Chinese.
Higher Handgrip Strength Is Linked to Better Cognitive Performance in Chinese Adults with Hypertension
Authors: Lu Shenghua , Herold Fabian , Zhang Yanjie , Lei Yuruo , Kramer Arthur F. , Jiao Can , Yu Qian , Doig Scott , Li Jinming , Yan Zhe , Kuang Jin , Wang Ting , Zou Liye
Published: July 2021

Objective: There is growing evidence that in adults, higher levels of handgrip strength (HGS) are linked to better cognitive performance. However, the relationship between HGS and cognitive performance has not been sufficiently investigated in special cohorts, such as individuals with hypertension who have an intrinsically higher risk of cognitive decline. Thus, the purpose of this study was to examine the relationship between HGS and cognitive performance in adults with hypertension using data from the Global Ageing and Adult Health Survey (SAGE). Methods: A total of 4486 Chinese adults with hypertension from the SAGE were included in this study. Absolute handgrip strength (aHGS in kilograms) was measured using a handheld electronic dynamometer, and cognitive performance was assessed in the domains of short-term memory, delayed memory, and language ability. Multiple linear regression models were fitted to examine the association between relative handgrip strength (rHGS; aHGS divided by body mass index) and measures of cognitive performance. Results: Overall, higher levels of rHGS were associated with higher scores in short-term memory (β = 0.20) and language (β = 0.63) compared with the lowest tertiles of rHGS. In male participants, higher HGS was associated with higher scores in short-term memory (β = 0.31), language (β = 0.64), and delayed memory (β = 0.22). There were no associations between rHGS and cognitive performance measures in females. Conclusion: We observed that a higher level of rHGS was associated with better cognitive performance among hypertensive male individuals. Further studies are needed to investigate the neurobiological mechanisms, including sex-specific differences driving the relationship between measures of HGS and cognitive performance in individuals with hypertension.
Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
Authors: Handlovic Troy T. , Moreira Tyler , Khan Anoshia , Saeed Haroon , Khan Yousuf , Elshaer Mohammed R. , Bogart Justin A.
Published: July 2021

Multidentate ligands involving tethered pyridyl groups coordinated to transition metal ions have been frequently used to mimic the 3-histidine (3H), 2-histidine-1-carboxylate (2H1C) brace motifs or other combinations of histidine and carboxylate endogenous ligating residues found in bioinorganic metalloenzymes. It is of interest to immobilize these ligand chelates onto heterogeneous supports. This, however, requires the use of bromine-substituted (chloromethyl)pyridines, whose current synthetic routes involve the use of extremely pyrophoric chemicals, such as n-butyllithium that require cryogenic reaction conditions, and toxic chemicals, such as thionyl chloride, that are challenging to handle and require extensive hazard controls. Herein, we report alternative methodologies towards the syntheses of 2-bromo-6-hydroxymethylpyridine and 2-bromo-6-chloromethylpyridine from inexpensive commercially available 2,6-dibromopyridine using isopropylmagnesium chloride lithium chloride complex (Turbo Grignard) and cyanuric chloride which are easier to handle and require milder reaction conditions than the conventional reagents. Gas chromatography-mass spectrometry (GC-MS) methods were developed and simple 1H- and 13C- nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) spectroscopies were also used to monitor the conversion of both reaction steps and showed that products could be obtained and isolated through simple workups without the presence of unreacted starting material or undesired overchlorinated 2-chloro-6-chloromethylpyridine side product.
Biomass-Derived Carbons as Versatile Materials for Energy-Related Applications: Capacitive Properties vs. Oxygen Reduction Reaction Catalysis
Authors: Breitenbach Stefan , Gavrilov Nemanja , Pašti Igor , Unterweger Christoph , Duchoslav Jiri , Stifter David , Hassel Achim Walter , Fürst Christian
Published: July 2021

Biomass-derived carbons are very attractive materials due to the possibility of tuning their properties for different energy-related applications. Various pore sizes, conductivities and the inherent presence of heteroatoms make them attractive for different electrochemical reactions, including the implementation of electrochemical capacitors or fuel cell electrodes. This contribution demonstrates how different biomass-derived carbons prepared from the same precursor of viscose fibers can reach appreciable capacitances (up to 200 F g−1) or a high selectivity for the oxygen reduction reaction (ORR). We find that a highly specific surface area and a large mesopore volume dominate the capacitive response in both aqueous and non-aqueous electrolytic solutions. While the oxygen reduction reaction activity is not dominated by the same factors at low ORR overpotentials, these take the dominant role over surface chemistry at high ORR overpotentials. Due to the high selectivity of the O2 reduction to peroxide and the appreciable specific capacitances, it is suggested that activated carbon fibers derived from viscose fibers are an attractive and versatile material for electrochemical energy conversion applications.
Lutetium-177 Labelled PSMA Targeted Therapy in Advanced Prostate Cancer: Current Status and Future Perspectives
Authors: Seitzer Konstantin Egon , Seifert Robert , Kessel Katharina , Roll Wolfgang , Schlack Katrin , Boegemann Martin , Rahbar Kambiz
Published: July 2021

Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option 177Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from 177Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a given fact, and with the newly published results of the VISION trial its approval is only a matter of time. Recently, investigators started to focus on treating prostate cancer patients in earlier disease stages and in combination with other compounds. This review gives a brief overview of the current state and the future perspectives of 177Lu labelled PSMA radioligand therapy.
Effectiveness of a Novel Covered Stent without External Thread Fixation for Anastomotic Leakage after Total or Proximal Gastrectomy for Gastric Cancer
Authors: Kim Young-Il , Kim Chan Gyoo , Lee Jong Yeul , Choi Il Ju , Eom Bang Wool , Yoon Hong Man , Ryu Keun Won , Kim Young-Woo
Published: July 2021

A thread-fix stent entails long hospitalization and patient discomfort. We aimed to evaluate the efficacy of a novel stent with silicone-covered outer double layers without external fixation (Beta stent) for anastomotic leakage after total or proximal gastrectomy. The outcomes were compared between gastric cancer patients who underwent stent placement using a thread-fix stent between 2014 and 2015 (Thread-Fix Group) and those who received a Beta stent in the succeeding period until October 2018 (Beta Stent Group). The Beta Stent Group (n = 14) had a significantly higher leakage healing rate by the first stent placement (92.9% vs. 53.8%; p = 0.021) and had a shorter hospitalization period (median: 16 days vs. 28 days; p = 0.037) than the Thread-Fix Group (n = 13). Further, 50% of the Beta stent patients received outpatient management until stent removal. Stent maintenance duration was significantly longer in the Beta Stent Group (median, 28 days vs. 18 days; p = 0.006). There was no significant between-group difference in stent-related complications except for stent migration (7.1% (Beta Stent Group) vs. 0% (Thread-Fix Group), p = 0.326). In conclusion, the Niti-S Beta stent is an effective treatment for anastomotic leakage from total or proximal gastrectomy for gastric cancer. Stent maintenance is possible without hospitalization.
Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients
Authors: Veltri Giulia , Silvestri Chiara , Gallingani Ilaria , Sandei Max , Vencato Sara , Lovisa Federica , Cortese Giuliana , Pillon Marta , Carraro Elisa , Bresolin Silvia , Biffi Alessandra , Basso Giuseppe , Accordi Benedetta , Mussolin Lara , Serafin Valentina
Published: July 2021

Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin lymphoma in childhood, mainly of T cell origin (T-LBL). Although current treatment protocols allow a complete remission in 85% of cases, the second-line treatment overall survival for patients with progressive or relapsed disease is around 14%, making this the major issue to be confronted. Thus, we performed a Reverse Phase Protein Array study in a cohort of 22 T-LBL patients to find reliable disease risk marker(s) and new therapeutic targets to improve pediatric T-LBL patients’ outcome. Interestingly, we pinpointed JAK2 Y1007-1008 as a potential prognosis marker as well as a therapeutic target in poor prognosis patients. Hence, the hyperactivation of the JAK1/2-STAT6 pathway characterizes these latter patients. Moreover, we functionally demonstrated that STAT6 hyperactivation contributes to therapy resistance by binding the glucocorticoid receptor, thus inhibiting its transcriptional activity. This was further confirmed by specific STAT6 gene silencing followed by dexamethasone treatment. Finally, JAK1/2-STAT6 pathway inhibition by ruxolitinib, an FDA approved drug, in cell line models and in one T-LBL primary sample led to cell proliferation reduction and increased apoptosis. Globally, our results identify a new potential prognostic marker and suggest a novel therapeutic approach to overcome therapy resistance in pediatric T-LBL patients.
Glycosylation: Rising Potential for Prostate Cancer Evaluation
Authors: Kałuża Anna , Szczykutowicz Justyna , Ferens-Sieczkowska Mirosława
Published: July 2021

Prostate cancer is the second most commonly diagnosed cancer among men. Alterations in protein glycosylation are confirmed to be a reliable hallmark of cancer. Prostate-specific antigen is the biomarker that is used most frequently for prostate cancer detection, although its lack of sensitivity and specificity results in many unnecessary biopsies. A wide range of glycosylation alterations in prostate cancer cells, including increased sialylation and fucosylation, can modify protein function and play a crucial role in many important biological processes in cancer, including cell signalling, adhesion, migration, and cellular metabolism. In this review, we summarize studies evaluating the prostate cancer associated glycosylation related alterations in sialylation, mainly α2,3-sialylation, core fucosylation, branched N-glycans, LacdiNAc group and presence of truncated O-glycans (sTn, sT antigen). Finally, we discuss the great potential to make use of glycans as diagnostic and prognostic biomarkers for prostate cancer.
The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment
Authors: Villa Federico , Bruno Silvia , Costa Ambra , Li Mingchuan , Russo Michele , Cimino James , Altieri Paola , Ruggeri Clarissa , Gorgun Cansu , De Biasio Pierangela , Paladini Dario , Coviello Domenico , Quarto Rodolfo , Ameri Pietro , Ghigo Alessandra , Ravera Silvia , Tasso Roberta , Bollini Sveva
Published: July 2021

Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotoxicity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been documented. We demonstrated that the human fetal amniotic fluid-stem cell (hAFS) secretome, namely the secreted paracrine factors within the hAFS-conditioned medium (hAFS-CM), exerts pro-survival effects on Dox-exposed cardiomyocytes. Here, we provide a detailed comparison of the cardioprotective potential of hAFS-CM over the secretome of mesenchymal stromal cells from adipose tissue (hMSC-CM). hAFS and hMSC were preconditioned under hypoxia to enrich their secretome. The cardioprotective effects of hAFS/hMSC-CM were evaluated on murine neonatal ventricular cardiomyocytes (mNVCM) and on their fibroblast counterpart (mNVFib), and their long-term paracrine effects were investigated in a mouse model of Dox-induced cardiomyopathy. Both secretomes significantly contributed to preserving mitochondrial metabolism within Dox-injured cardiac cells. hAFS-CM and hMSC-CM inhibited body weight loss, improved myocardial function, reduced lipid peroxidation and counteracted the impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis induced by Dox. The hAFS and hMSC secretomes can be exploited for inhibiting cardiotoxic detrimental side effects of Dox during cancer therapy, thus ensuring cardioprotection via combinatorial paracrine therapy in association with standard oncological treatments.
5,6-Epoxycholesterol Isomers Induce Oxiapoptophagy in Myeloma Cells
Authors: Jaouadi Oumaima , Limam Inès , Abdelkarim Mohamed , Berred Emna , Chahbi Ahlem , Caillot Mélody , Sola Brigitte , Ben Aissa-Fennira Fatma
Published: July 2021

Multiple myeloma (MM) is an incurable plasma cell malignancy with frequent patient relapse due to innate or acquired drug resistance. Cholesterol metabolism is reported to be altered in MM; therefore, we investigated the potential anti-myeloma activity of two cholesterol derivatives: the 5,6 α- and 5,6 β-epoxycholesterol (EC) isomers. To this end, viability assays were used, and isomers were shown to exhibit important anti-tumor activity in vitro in JJN3 and U266 human myeloma cell lines (HMCLs) and ex vivo in myeloma patients’ sorted CD138+ malignant cells. Moreover, we confirmed that 5,6 α-EC and 5,6 β-EC induced oxiapoptophagy through concomitant oxidative stress and caspase-3-mediated apoptosis and autophagy. Interestingly, in combination treatment a synergistic interaction was observed between 5,6 α-EC and 5,6 β-EC on myeloma cells. These data highlight a striking anti-tumor activity of 5,6 α-EC and 5,6 β-EC bioactive molecules against human myeloma cells, paving the way for their potential role in future therapeutic strategies in MM.
Iridium Complex Catalyzed Hydrogen Production from Glucose and Various Monosaccharides
Authors: Fujita Ken-ichi , Inoue Takayoshi , Tanaka Toshiki , Jeong Jaeyoung , Furukawa Shohichi , Yamaguchi Ryohei
Published: July 2021

A new catalytic system has been developed for hydrogen production from various monosaccharides, mainly glucose, as a starting material under reflux conditions in water in the presence of a water-soluble dicationic iridium complex bearing a functional bipyridine ligand. For example, the reaction of D-glucose in water under reflux for 20 h in the presence of [Cp*Ir(6,6′-dihydroxy-2,2′-bipyridine)(H2O)][OTf]2 (1.0 mol %) (Cp*: pentamethylcyclopentadienyl, OTf: trifluoromethanesulfonate) resulted in the production of hydrogen gas in 95% yield. In the present catalytic reaction, it was experimentally suggested that dehydrogenation of the alcoholic moiety at 1-position of glucose proceeded.
Rational Design of Non-Precious Metal Oxide Catalysts by Means of Advanced Synthetic and Promotional Routes
Authors: Konsolakis Michalis , Stathopoulos Vassilis N.
Published: July 2021

Catalysis is an indispensable part of our society, involved in numerous energy and environmental applications, such as the production of value-added chemicals/fuels, hydrocarbons processing, fuel cells applications, abatement of hazardous pollutants, among others [...]
Synthesis of n-Alkoxy Derivatives of Layered Perovskite-Like Niobate HCa2Nb3O10 and Study of Their Photocatalytic Activity for Hydrogen Production from an Aqueous Solution of Methanol
Authors: Voytovich Vladimir , Kurnosenko Sergey , Silyukov Oleg , Rodionov Ivan , Bugrov Alexander , Minich Iana , Malygina Ekaterina , Zvereva Irina
Published: July 2021

A series of hybrid inorganic–organic niobates HCa2Nb3O10×ROH, containing n-alkoxy groups of primary alcohols (R = Me, Et, Pr, Bu, Hx, and Dc) grafted in the interlayer space, has been studied for the first time in relation to photocatalytic hydrogen generation from a model 1 mol % aqueous solution of methanol under ultraviolet irradiation. Photocatalytic activity was measured both for bare samples and for their composites with Pt nanoparticles as a cocatalyst. The advanced measurement scheme allowed monitoring the volume concentration of a sample in a suspension during the experiment, its pH, and possible exfoliation of layered compounds into nanolayers. In the series of n-alkoxy derivatives, the maximum rate of hydrogen evolution was achieved over a Pt-loaded ethoxy derivative HCa2Nb3O10×EtOH/Pt. Its apparent quantum efficiency of 20.6% in the 220–350 nm range was found not to be caused by changes in the light absorption region or specific surface area upon ethanol grafting. Moreover, the amounts of hydrogen released during the measurements significantly exceeded those of interlayer organic components, indicating that hydrogen is generated from the reaction solution rather than from the hybrid material.
Analysis of Photocatalytic Degradation of Phenol with Exfoliated Graphitic Carbon Nitride and Light-Emitting Diodes Using Response Surface Methodology
Authors: Rana Adeem Ghaffar , Minceva Mirjana
Published: July 2021

Response surface methodology (RSM) involving a Box–Benkhen design (BBD) was employed to analyze the photocatalytic degradation of phenol using exfoliated graphitic carbon nitride (g-C3N4) and light-emitting diodes (wavelength = 430 nm). The interaction between three parameters, namely, catalyst concentration (0.25–0.75 g/L), pollutant concentration (20–100 ppm), and pH of the solution (3–10), was examined and modeled. An empirical regression quadratic model was developed to relate the phenol degradation efficiency with these three parameters. Analysis of variance (ANOVA) was then applied to examine the significance of the model; this showed that the model is significant with an insignificant lack of fit and an R2 of 0.96. The statistical analysis demonstrated that, in the studied range, phenol concentration considerably affected phenol degradation. The RSM model shows a significant correlation between predicted and experimental values of photocatalytic degradation of phenol. The model’s accuracy was tested for 50 ppm of phenol under optimal conditions involving a catalyst concentration of 0.4 g/L catalysts and a solution pH of 6.5. The model predicted a degradation efficiency of 88.62%, whereas the experimentally achieved efficiency was 83.75%.
Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction
Authors: Dahlström Märta , Madjid Nather , Nordvall Gunnar , Halldin Magnus M. , Vazquez-Juarez Erika , Lindskog Maria , Sandin Johan , Winblad Bengt , Eriksdotter Maria , Forsell Pontus
Published: July 2021

Alzheimer’s disease (AD) is the most common neurodegenerative disorder and results in severe neurodegeneration and progressive cognitive decline. Neurotrophins are growth factors involved in the development and survival of neurons, but also in underlying mechanisms for memory formation such as hippocampal long-term potentiation. Our aim was to identify small molecules with stimulatory effects on the signaling of two neurotrophins, the nerve growth factor (NGF) and the brain derived neurotrophic factor (BDNF). To identify molecules that could potentiate neurotrophin signaling, 25,000 molecules were screened, which led to the identification of the triazinetrione derivatives ACD855 (Ponazuril) and later on ACD856, as positive allosteric modulators of tropomyosin related kinase (Trk) receptors. ACD855 or ACD856 potentiated the cellular signaling of the neurotrophin receptors with EC50 values of 1.9 and 3.2 or 0.38 and 0.30 µM, respectively, for TrkA or TrkB. ACD855 increased acetylcholine levels in the hippocampus by 40% and facilitated long term potentiation in rat brain slices. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several different behavioral models. Finally, the age-induced cognitive dysfunction in 18-month-old mice could be restored to the same level as found in 2-month-old mice after a single treatment of ACD856. We have identified a novel mechanism to modulate the activity of the Trk-receptors. The identification of the positive allosteric modulators of the Trk-receptors might have implications for the treatment of Alzheimer’s diseases and other diseases characterized by cognitive impairment.
Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles
Authors: Guo Shaowei , Redenski Idan , Levenberg Shulamit
Published: July 2021

Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting “cell-free” therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.
Effect of Low Temperature on Changes in AGP Distribution during Development of Bellis perennis Ovules and Anthers
Authors: Leszczuk Agata , Szczuka Ewa , Lewtak Kinga , Chudzik Barbara , Zdunek Artur
Published: July 2021

Arabinogalactan proteins (AGPs) are a class of heavily glycosylated proteins occurring as a structural element of the cell wall-plasma membrane continuum. The features of AGPs described earlier suggest that the proteins may be implicated in plant adaptation to stress conditions in important developmental phases during the plant reproduction process. In this paper, the microscopic and immunocytochemical studies conducted using specific antibodies (JIM13, JIM15, MAC207) recognizing the carbohydrate chains of AGPs showed significant changes in the AGP distribution in female and male reproductive structures during the first stages of Bellis perennis development. In typical conditions, AGPs are characterized by a specific persistent spatio-temporal pattern of distribution. AGP epitopes are visible in the cell walls of somatic cells and in the megasporocyte walls, megaspores, and embryo sac at every stage of formation. During development in stress conditions, the AGP localization is altered, and AGPs entirely disappear in the embryo sac wall. In the case of male development, AGPs are present in the tapetum, microsporocytes, and microspores in normal conditions. In response to development at lower temperature, AGPs are localized in the common wall of microspores and in mature pollen grains. Additionally, they are accumulated in remnants of tapetum cells.
Role of Nrf2 in Synaptic Plasticity and Memory in Alzheimer’s Disease
Authors: Davies Don A. , Adlimoghaddam Aida , Albensi Benedict C.
Published: July 2021

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that reduces oxidative stress. When reactive oxygen species (ROS) or reactive nitrogen species (RNS) are detected, Nrf2 translocates from the cytoplasm into the nucleus and binds to the antioxidant response element (ARE), which regulates the expression of antioxidant and anti-inflammatory genes. Nrf2 impairments are observed in the majority of neurodegenerative disorders, including Alzheimer’s disease (AD). The classic hallmarks of AD include β-amyloid (Aβ) plaques, and neurofibrillary tangles (NFTs). Oxidative stress is observed early in AD and is a novel therapeutic target for the treatment of AD. The nuclear translocation of Nrf2 is impaired in AD compared to controls. Increased oxidative stress is associated with impaired memory and synaptic plasticity. The administration of Nrf2 activators reverses memory and synaptic plasticity impairments in rodent models of AD. Therefore, Nrf2 activators are a potential novel therapeutic for neurodegenerative disorders including AD.
Plasticity of the Injured Spinal Cord
Authors: Guérout Nicolas
Published: July 2021

Complete spinal cord injury (SCI) leads to permanent motor, sensitive and sensory deficits. In humans, there is currently no therapy to promote recovery and the only available treatments include surgical intervention to prevent further damage and symptomatic relief of pain and infections in the acute and chronic phases, respectively. Basically, the spinal cord is classically viewed as a nonregenerative tissue with limited plasticity. Thereby the establishment of the “glial” scar which appears within the SCI is mainly described as a hermetic barrier for axon regeneration. However, recent discoveries have shed new light on the intrinsic functional plasticity and endogenous recovery potential of the spinal cord. In this review, we will address the different aspects that the spinal cord plasticity can take on. Indeed, different experimental paradigms have demonstrated that axonal regrowth can occur even after complete SCI. Moreover, recent articles have demonstrated too that the “glial” scar is in fact composed of several cellular populations and that each of them exerts specific roles after SCI. These recent discoveries underline the underestimation of the plasticity of the spinal cord at cellular and molecular levels. Finally, we will address the modulation of this endogenous spinal cord plasticity and the perspectives of future therapeutic opportunities which can be offered by modulating the injured spinal cord microenvironment.
Mitochondrial Dysfunction and Mitophagy in Fuchs Endothelial Corneal Dystrophy
Authors: Kumar Varun , Jurkunas Ula V.
Published: July 2021

Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, heterogenous, age-related degenerative disease of corneal endothelial cells (CEnCs), occurring in the fifth decade of life with a higher incidence in females. It is characterized by extracellular matrix (ECM) protein deposition called corneal guttae, causing light glare and visual complaints in patients. Corneal transplantation is the only treatment option for FECD patients, which imposes a substantial socioeconomic burden. In FECD, CEnCs exhibit stress-induced senescence, oxidative stress, DNA damage, heightened reactive oxygen species (ROS) production, mitochondrial damage, and dysfunction as well as sustained endoplasmic reticulum (ER) stress. Among all of these, mitochondrial dysfunction involving altered mitochondrial bioenergetics and dynamics plays a critical role in FECD pathogenesis. Extreme stress initiates mitochondrial damage, leading to activation of autophagy, which involves clearance of damaged mitochondria called auto(mito)phagy. In this review, we discuss the role of mitochondrial dysfunction and mitophagy in FECD. This will provide insights into a novel mechanism of mitophagy in post-mitotic ocular cell loss and help us explore the potential treatment options for FECD.
The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection
Authors: Conceição-Silva Fátima , Reis Clarissa S. M. , De Luca Paula Mello , Leite-Silva Jessica , Santiago Marta A. , Morrot Alexandre , Morgado Fernanda N.
Published: July 2021

The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described—suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.
An Active Surface Preservation Strategy for the Rational Development of Carbon Dots as pH-Responsive Fluorescent Nanosensors
Authors: Afonso Ana Carolina P. , Correia Ana Salomé , Duarte Diana , Brandão Ana T. S. C. , de Yuso Maria del Valle Martínez , Jiménez-Jiménez José , Vale Nuno , Pereira Carlos M. , Algarra Manuel , Pinto da Silva Luís
Published: July 2021

Here we report the rational development of a carbon dot (CDs)-based fluorescent pH nanosensor by employing an active surface preservation strategy. More specifically, citric acid, urea and fluorescein were subjected to a one-pot hydrothermal treatment, which preserved fluorescein-like structures on the surface of the CDs. The obtained CDs showed pH-sensitive green emission, which can be used to determine pH variations from 3.7 to 12.1 by fluorescence enhancement. Moreover, the obtained nanoparticles showed excellent selectivity toward pH, fluorescence reversibility in different pH values, photostability, while being compatible with human cell lines (even at high concentrations). Furthermore, their performance as pH sensors was comparable with reference pH determination procedures. Thus, an active surface preservation strategy was successfully employed to develop fluorescence pH nanosensors in a rational manner and without post-synthesis functionalization strategies, which show potential for future use in pH determination.