bluuebunny/crossref_metadata_2025 huggingface dataset:
Androstenedione and Follicle-Stimulating Hormone Concentration Predict the Progression of Frailty Syndrome at One Year Follow-Up in Patients with Localized Breast Cancer Treated with Aromatase Inhibitors
Authors: García-Sánchez Javier , Mafla-España Mayra Alejandra , Torregrosa María Dolores , Cauli Omar
Published: July 2022

Background: The standard treatment in postmenopausal women with estrogen- and progesterone-positive localized breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen frailty syndrome over time and the relationship with changes in gonadal hormones concentration in blood have not been investigated. Methods: A prospective study to evaluate the relationship between frailty syndrome and gonadal hormones concentrations in blood at baseline (prior to AROi treatment) and after 6 and 12 months under AROi treatment in post-menopausal women with breast cancer. Frailty syndrome was evaluated by the Fried’ criteria. We evaluated whether hormone concentration at baseline could predict frailty syndrome at follow-up. Results: Multinomial regression analysis showed that of the different hormones, those significantly (p < 0.05) associated to the worsening of frailty syndrome were high androstenedione levels and low follicle-stimulating hormone (FSH) levels in blood. Receiver operating characteristic curve analysis showed both androstenedione and FSH significantly (p < 0.05) discriminate patients who developed or presented worsening of frailty syndrome over time, with acceptable sensitivity (approximately 80% in both cases) but low specificity (40%). Conclusion: Hormonal concentrations before AROi treatment constitute possible biomarkers to predict the progression of frailty syndrome.
Susceptibility of Drug Resistant Hepatitis B Virus Mutants to Besifovir
Authors: Won Juhee , Lee Ah Ram , Dezhbord Mehrangiz , Lee Da Rae , Kim Seong Ho , Kim Jong Chul , Park Soree , Kim Nayeon , Jae Byengjune , Kim Kyun-Hwan
Published: July 2022

Currently, interferon alpha and nucleos(t)ide analogues (NAs) are clinically available to treat hepatitis B virus (HBV) infection. Several NAs, including lamivudine (LMV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF or TAF) have been approved and administered to chronic hepatitis B (CHB) patients. NAs inhibit HBV DNA synthesis by targeting the reverse transcriptase (RT) domain of HBV polymerase. Several mutations in the RT domain which lead to drug resistance against NAs have been reported, even for TDF and TAF which are highly potent with very low resistance rate. Besifovir (BFV) is a new antiviral dGMP analogue able to be used as a new NA drug for the control of CHB infection. Drug resistance to BFV is not well known due to its shorter duration of clinical use. Recently, we reported that rtL180M (M) and rtM204V (V) mutations, already resistant to LMV, are associated with BFV resistance. However, the susceptibility to BFV of previously known HBV mutants resistant to various drugs has not been studied. To investigate this, we performed in vitro drug susceptibility assays using natural and artificial mutants that are associated with resistance to LMV, ADV, ETV or TDF. As a result, LMV-resistant mutants were not susceptible to BFV and ETV-resistant clones showed partial resistance against BFV as well. However, ADV-resistant mutants were highly sensitive to BFV. In case of tenofovir-resistant mutations, the HBV mutants harboring primary mutations to tenofovir resistance were susceptible to BFV. Therefore, our study revealed that BSV may serve as an alternative drug for patients with ADV-, ETV-, TDF- or TAF-resistance.
Emodin Ameliorates the Efficacy of Carfilzomib in Multiple Myeloma Cells via Apoptosis and Autophagy
Authors: Hsu Chin-Mu , Yen Chia-Hung , Wang Shu-Chen , Liu Yi-Chang , Huang Chien-Tzu , Wang Min-Hong , Chuang Tzer-Ming , Ke Ya-Lun , Yeh Tsung-Jang , Gau Yuh-Ching , Du Jeng-Shiun , Wang Hui-Ching , Cho Shih-Feng , Tsai Yuhsin , Hsiao Chi-En , Hsiao Samuel Yien , Hsiao Hui-Hua
Published: July 2022

Background: Carfilzomib, the proteasome inhibitor, can increase the overall survival rate of multiple myeloma (MM) patients undergoing targeted therapy. However, relapse and toxicity present great challenges for such treatment, so an urgent need for effective combination therapy is necessary. Emodin is a natural chemical compound that inhibits the proliferation of various cancers and can effectively combine with other treatments. In this study, we evaluated the sensitizing effect of emodin combined with carfilzomib on MM cells. Methods: The cells were treated with emodin, carfilzomib, and a combination of drugs to determine their effects on cell proliferation and viability. The cell cycle distribution and reactive oxygen species (ROS) expression were measured by flow cytometry. The level of RNA and protein were analyzed through real-time qPCR and immunoblotting. Results: Emodin acted synergistically with carfilzomib to reduce the proliferation and viability of MM cell lines in vitro. Furthermore, the combination of emodin and carfilzomib increased ROS production, inducing apoptosis and autophagy pathways via caspase-3, PARP, p62, and LC3B. Conclusions: These results provide a molecular target for combination therapy in MM patients.
Optical Behavior of Human Skin Substitutes: Absorbance in the 200–400 nm UV Range
Authors: Ruiz-López Javier , Cardona Juan C. , Garzón Ingrid , Pérez María M. , Alaminos Miguel , Chato-Astrain Jesus , Ionescu Ana M.
Published: July 2022

The most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200–280 nm), -B (280–315 nm), and -A (315–400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development. The epidermis of the bioartificial skin substitute was able to mature and differentiate in a time-dependent manner, expressing relevant molecules able to absorb most of the incoming UV radiation. Absorbance spectral behavior of the skin substitutes showed similar patterns to control native skin (VAF > 99.4%), with values 0.85–0.90 times lower than control values at 7 and 14- days and 1.05–1.10 times the control values at 21- and 28-days. UV absorbance increased, and UV transmission decreased with culture time, and comparable results to the control were found at 21 and 28 days. These findings support the use of samples corresponding to 21 or 28 days of development for clinical purposes due to their higher histological similarities with native skin, but also because of their absorbance of UV radiation.
A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight
Authors: Katayama Daichi , Nagano Nobuhiko , Shimizu Shoichi , Nakazaki Kimitaka , Matsuda Kengo , Tokunaga Wataru , Fuwa Kazumasa , Aoki Ryoji , Morioka Ichiro
Published: July 2022

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.
circRNA: A New Biomarker and Therapeutic Target for Esophageal Cancer
Authors: Shoda Katsutoshi , Kuwano Yuki , Ichikawa Daisuke , Masuda Kiyoshi
Published: July 2022

Circular RNAs (circRNAs) comprise a large class of endogenous non-coding RNA with covalently closed loops and have independent functions as linear transcripts transcribed from identical genes. circRNAs are generated by a “back-splicing” process regulated by regulatory elements in cis and associating proteins in trans. Many studies have shown that circRNAs play important roles in multiple processes, including splicing, transcription, chromatin modification, miRNA sponges, and protein decoys. circRNAs are highly stable because of their closed ring structure, which prevents them from degradation by exonucleases, and are more abundant in terminally differentiated cells, such as brains. Recently, it was demonstrated that numerous circRNAs are differentially expressed in cancer cells, and their dysfunction is involved in tumorigenesis and metastasis. However, the crucial functions of these circRNAs and the dysregulation of circRNAs in cancer are still unknown. In this review, we summarize the recent reports on the biogenesis and biology of circRNAs and then catalog the advances in using circRNAs as biomarkers and therapeutic targets for cancer therapy, particularly esophageal cancer.
Metformin Is Associated with the Inhibition of Renal Artery AT1R/ET-1/iNOS Axis in a Rat Model of Diabetic Nephropathy with Suppression of Inflammation and Oxidative Stress and Kidney Injury
Authors: Dawood Amal F. , Maarouf Amro , Alzamil Norah M. , Momenah Maha A. , Shati Ayed A. , Bayoumy Nervana M. , Kamar Samaa S. , Haidara Mohamed A. , ShamsEldeen Asmaa M. , Yassin Hanaa Z. , Hewett Peter W. , Al-Ani Bahjat
Published: July 2022

Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.
β-Adrenergic Receptor Stimulation Maintains NCX-CaMKII Axis and Prevents Overactivation of IL6R-Signaling in Cardiomyocytes upon Increased Workload
Authors: Matzer Ingrid , Voglhuber Julia , Kiessling Mara , Djalinac Nataša , Trummer-Herbst Viktoria , Mabotuwana Nishani , Rech Lavinia , Holzer Michael , Sossalla Samuel , Rainer Peter P. , Zirlik Andreas , Ljubojevic-Holzer Senka
Published: July 2022

Excessive β-adrenergic stimulation and tachycardia are potent triggers of cardiac remodeling; however, their exact cellular effects remain elusive. Here, we sought to determine the potency of β-adrenergic stimulation and tachycardia to modulate gene expression profiles of cardiomyocytes. Using neonatal rat ventricular cardiomyocytes, we showed that tachycardia caused a significant upregulation of sodium–calcium exchanger (NCX) and the activation of calcium/calmodulin-dependent kinase II (CaMKII) in the nuclear region. Acute isoprenaline treatment ameliorated NCX-upregulation and potentiated CaMKII activity, specifically on the sarcoplasmic reticulum and the nuclear envelope, while preincubation with the β-blocker propranolol abolished both isoprenaline-mediated effects. On a transcriptional level, screening for hypertrophy-related genes revealed tachycardia-induced upregulation of interleukin-6 receptor (IL6R). While isoprenaline prevented this effect, pharmacological intervention with propranolol or NCX inhibitor ORM-10962 demonstrated that simultaneous CaMKII activation on the subcellular Ca2+ stores and prevention of NCX upregulation are needed for keeping IL6R activation low. Finally, using hypertensive Dahl salt-sensitive rats, we showed that blunted β-adrenergic signaling is associated with NCX upregulation and enhanced IL6R signaling. We therefore propose a previously unrecognized protective role of β-adrenergic signaling, which is compromised in cardiac pathologies, in preventing IL6R overactivation under increased workload. A better understanding of these processes may contribute to refinement of therapeutic options for patients receiving β-blockers.
How Structural Features Define Biogenesis and Function of Human Telomerase RNA Primary Transcript
Authors: Rubtsova Maria , Dontsova Olga
Published: July 2022

Telomerase RNA has been uncovered as a component of the telomerase enzyme, which acts as a reverse transcriptase and maintains the length of telomeres in proliferated eukaryotic cells. Telomerase RNA is considered to have major functions as a template for telomeric repeat synthesis and as a structural scaffold for telomerase. However, investigations of its biogenesis and turnover, as well as structural data, have provided evidence of functions of telomerase RNA that are not associated with telomerase activity. The primary transcript produced from the human telomerase RNA gene encodes for the hTERP protein, which presents regulatory functions related to autophagy, cellular proliferation, and metabolism. This review focuses on the specific features relating to the biogenesis and structure of human telomerase RNA that support the existence of an isoform suitable for functioning as an mRNA. We believe that further investigation into human telomerase RNA biogenesis mechanisms will provide more levels for manipulating cellular homeostasis, survival, and transformation mechanisms, and may contribute to a deeper understanding of the mechanisms of aging.
Isolation and Characterization of Extracellular Vesicles from Gastric Juice
Authors: Skryabin Gleb O. , Vinokurova Svetlana V. , Galetsky Sergey A. , Elkin Danila S. , Senkovenko Alexey M. , Denisova Darya A. , Komelkov Andrey V. , Stilidi Ivan S. , Peregorodiev Ivan N. , Malikhova Olga A. , Imaraliev Oiatiddin T. , Enikeev Adel D. , Tchevkina Elena M.
Published: July 2022

EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers.
Insomnia Symptoms and Daytime Fatigue Co-Occurrence in Adolescent and Young Adult Childhood Cancer Patients in Follow-Up after Treatment: Prevalence and Associated Risk Factors
Authors: Peersmann Shosha H. M. , Grootenhuis Martha A. , van Straten Annemieke , Tissing Wim J. E. , Abbink Floor , de Vries Andrica C. H. , Loonen Jacqueline , van der Pal Helena J. H. , Kaspers Gertjan J. L. , van Litsenburg Raphaële R. L.
Published: July 2022

Insomnia symptoms and daytime fatigue commonly occur in pediatric oncology, which significantly impact physical and psychosocial health. This study evaluated the prevalence of insomnia only, daytime fatigue only, the co-occurrence of insomnia–daytime fatigue symptoms, and associated risk factors. Childhood cancer patients (n = 565, 12–26 years old, ≥6 months after treatment) participated in a national, cross-sectional questionnaire study, measuring insomnia symptoms (ISI; Insomnia Severity Index) and daytime fatigue (single item). Prevalence rates of insomnia and/or daytime fatigue subgroups and ISI severity ranges were calculated. Multinomial regression models were applied to assess risk factors. Most patients reported no insomnia symptoms or daytime fatigue (61.8%). In the 38.2% of patients who had symptoms, 48.1% reported insomnia and daytime fatigue, 34.7% insomnia only, and 17.1% daytime fatigue only. Insomnia scores were higher in patients with insomnia–daytime fatigue compared to insomnia only (p < 0.001). Risk factors that emerged were: female sex and co-morbidities (all), shorter time after treatment and bedtime gaming (insomnia only), young adulthood (insomnia–fatigue/fatigue only), needing someone else to fall asleep and inconsistent wake times (both insomnia groups), lower educational level and consistent bedtimes (insomnia–fatigue). Insomnia symptoms and daytime fatigue are common and often co-occur. While current fatigue guidelines do not include insomnia symptoms, healthcare providers should inquire about insomnia as this potentially provides additional options for treatment and prevention.
Factors Contributing to Tumor Shrinkage after Peptide Receptor Radionuclide Therapy in Patients with Unresectable Neuroendocrine Tumors
Authors: Hasegawa Sho , Kobayashi Noritoshi , Wild Damian , Kaul Fesupplix , Okubo Naoki , Suzuki Akihiro , Kurita Yusuke , Takano Shoko , Nakajima Atsushi , Ichikawa Yasushi
Published: July 2022

Peptide receptor activation therapy (PRRT) is a promising treatment option for metastatic neuroendocrine tumors (NETs). However, predicting tumor shrinkage before treatment is challenging. We analyzed the shrinkage rate of each metastatic tumor lesion to identify predictive factors related to shrinkage. Patients with metastatic NET who underwent PRRT were included in this retrospective study. For each patient, between one to five metastatic lesions were selected in descending order of size, and the change in the maximum tumor diameter after treatment was defined as the shrinkage rate per lesion (L-SR). We analyzed the relationship between pretreatment clinicopathological factors and L-SR. The median L-SR of all 75 lesions in 20 patients was 20% (95% CI: 4.8–26.1%). While previous treatment with cytotoxic agents (34.4%, p < 0.05) and primary tumor of the pancreas (27.8%, p < 0.05) were significantly favorable factors, a primary tumor of the rectum was significantly more resistant to shrinkage (−20.5%, p < 0.001). Therefore, lesion-based analysis of PRRT for NETs showed that pancreatic NET and previous treatment with cytotoxic agents were favorable factors for tumor shrinkage; however, rectal NET was a factor associated with resistance to shrinkage.
The Potential of Novel Lipid Agents for the Treatment of Chemotherapy-Resistant Human Epithelial Ovarian Cancer
Authors: Nachtigal Mark W. , Altman Alon D. , Arora Rajat , Schweizer Frank , Arthur Gilbert
Published: July 2022

Recurrent epithelial ovarian cancer (EOC) coincident with chemotherapy resistance remains the main contributor to patient mortality. There is an ongoing investigation to enhance patient progression-free and overall survival with novel chemotherapeutic delivery, such as the utilization of antiangiogenic medications, PARP inhibitors, or immune modulators. Our preclinical studies highlight a novel tool to combat chemotherapy-resistant human EOC. Glycosylated antitumor ether lipids (GAELs) are synthetic glycerolipids capable of killing established human epithelial cell lines from a wide variety of human cancers, including EOC cell lines representative of different EOC histotypes. Importantly, GAELs kill high-grade serous ovarian cancer (HGSOC) cells isolated from the ascites of chemotherapy-sensitive and chemotherapy-resistant patients grown as monolayers of spheroid cultures. In addition, GAELs were well tolerated by experimental animals (mice) and were capable of reducing tumor burden and blocking ascites formation in an OVCAR-3 xenograft model. Overall, GAELs show great promise as adjuvant therapy for EOC patients with or without chemotherapy resistance.
Sex Differences in Taxane Toxicities
Authors: Chmielewski Nicole N. , Limoli Charles L.
Published: July 2022

The taxane family of microtubule poisons and chemotherapeutics have been studied for over 50 years and are among the most frequently used antineoplastic agents today. Still, limited research exists characterizing taxane-induced sex-specific mechanisms of action and toxicities in cancer and non-cancerous tissue. Such research is important to advance cancer treatment outcomes as well as to address clinically observed sex-differences in short- and long-term taxane-induced toxicities that have disproportionate effects on female and male cancer patients. To gain more insight into these underlying differences between the sexes, the following review draws from pre-clinical and clinical paclitaxel and taxane oncology literature, examines sex-discrepancies, and highlights uncharacterized sex-dependent mechanisms of action and clinical outcomes. To our knowledge, this is the first literature review to provide a current overview of the basic and clinical sex dimorphisms of taxane-induced effects. Most importantly, we hope to provide a starting point for improving and advancing sex-specific personalized chemotherapy and cancer treatment strategies as well as to present a novel approach to review sex as a biological variable in basic and clinical biology.
The Role of Metabolic Plasticity of Tumor-Associated Macrophages in Shaping the Tumor Microenvironment Immunity
Authors: Hasan Md Nabiul , Capuk Okan , Patel Shivani M. , Sun Dandan
Published: July 2022

Cancer cells possess a high metabolic demand for their rapid proliferation, survival, and progression and thus create an acidic and hypoxic tumor microenvironment (TME) deprived of nutrients. Moreover, acidity within the TME is the central regulator of tumor immunity that influences the metabolism of the immune cells and orchestrates the local and systemic immunity, thus, the TME has a major impact on tumor progression and resistance to anti-cancer therapy. Specifically, myeloid cells, which include myeloid-derived suppressor cells (MDSC), dendritic cells, and tumor-associated macrophages (TAMs), often reprogram their energy metabolism, resulting in stimulating the angiogenesis and immunosuppression of tumors. This review summarizes the recent findings of glucose, amino acids, and fatty acid metabolism changes of the tumor-associated macrophages (TAMs), and how the altered metabolism shapes the TME and anti-tumor immunity. Multiple proton pumps/transporters are involved in maintaining the alkaline intracellular pH which is necessary for the glycolytic metabolism of the myeloid cells and acidic TME. We highlighted the roles of these proteins in modulating the cellular metabolism of TAMs and their potential as therapeutic targets for improving immune checkpoint therapy.
Impact and Novel Perspective of Immune Checkpoint Inhibitors in Patients with Early and Intermediate Stage HCC
Authors: Marzi Luca , Mega Andrea , Gitto Stefano , Pelizzaro Filippo , Seeber Andreas , Spizzo Gilbert
Published: July 2022

Surgery and radiofrequency ablation remain the gold standard to achieve cure in patients with hepatocellular carcinoma (HCC). After a decade in which only sorafenib was available for advanced and metastatic HCC, the emergence of other molecularly targeted drugs and immune checkpoint inhibitors (ICIs) has significantly improved the patients` prognosis. In particular, the use of ICIs has shown promising results and has revolutionized the treatment algorithm in HCC patients. Indeed, preclinical and clinical data have documented a high density of immunosuppressive cells and an increased expression of the programmed death-1 (PD-1) receptor and cytotoxic T-cell associated protein-4 (CTLA-4) in HCC. However, despite these observations, no validated biomarker is available and the molecular groundwork responsible for response to ICIs remains elusive. The anti-CTLA4 monoclonal antibody tremelimumab and the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab were the first ICIs to be tested in HCC. Recently, the combination of the anti-programmed death-ligand 1 (PD-L1) inhibitor atezolizumab and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab demonstrated an improvement in patient outcome compared to sorafenib, becoming the standard of care in the frontline setting of advanced disease. Other immunotherapeutic agents such as pembrolizumab or the combination nivolumab-ipilimumab have shown promising results that have to be confirmed in phase III studies. Currently, the combination of different ICIs (i.e., ipilimumab, durvalumab) and anti-angiogenic agents (i.e., regorafenib, lenvatinib) is currently being tested in several trials and will hopefully revolutionize the treatment of HCC. To date, numerous studies are underway evaluating ICIs in adjuvant and neoadjuvant settings to improve survival in early and intermediate stages. Thus, this review focuses on the rationale for ICIs and their potential use for early or intermediate HCC stages.
The Impact of Resolution of Inflammation on Tumor Microenvironment: Exploring New Ways to Control Cancer Progression
Authors: Liotti Federica , Marotta Maria , Melillo Rosa Marina , Prevete Nella
Published: July 2022

Non-resolving inflammation is an enabling feature of cancer. A novel super-family of lipid mediators termed Specialized Pro-resolving Mediators (SPMs) have a role as bioactive molecules mediating the resolution of inflammation in cancer biology. SPMs are derived from ω-3 and ω-6 polyunsaturated fatty acids through the activity of lipoxygenases. SPMs have been described to directly modulate cancer progression by interfering with the epithelial to mesenchymal transition and invasion of cancer cells. SPMs have also been demonstrated to act on several components of the tumor microenvironment (TME). Consistently with their natural immunomodulatory and anti-inflammatory properties, SPMs are able to reprogram macrophages to favor phagocytosis of cell debris, which are an important source of pro-inflammatory and pro-angiogenic signals; sustain a direct cytotoxic immune response against cancer cells; stimulate neutrophils anti-tumor activities; and inhibit the development of regulatory T and B cells, thus indirectly leading to enhanced anti-tumor immunity. Furthermore, the resolution pathways exert crucial anti-angiogenic functions in lung, liver, and gastrointestinal cancers, and inhibit cancer-associated fibroblast differentiation and functions in hepatocellular carcinoma and pancreatic cancer. The present review will be focused on the potential protective effects of resolution pathways against cancer, exerted by modulating different components of the TME.
Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience
Authors: Heinzel Alexander , Dedic Daniela , Galldiks Norbert , Lohmann Philipp , Stoffels Gabriele , Filss Christian P. , Kocher Martin , Migliorini Filippo , Dillen Kim N. H. , Geisler Stefanie , Stegmayr Carina , Willuweit Antje , Sabel Michael , Rapp Marion , Eble Michael J. , Piroth Marc , Clusmann Hans , Delev Daniel , Bauer Elena K. , Ceccon Garry , Dunkl Veronika , Rosen Jurij , Tscherpel Caroline , Werner Jan-Michael , Ruge Maximilian I. , Goldbrunner Roland , Hampl Jürgen , Weiss Lucas Carolin , Herrlinger Ulrich , Maurer Gabriele D. , Steinbach Joachim P. , Mauler Jörg , Worthoff Wieland A. , Neumaier Bernd N. , Lerche Christoph , Fink Gereon R. , Shah Nadim Jon , Mottaghy Felix M. , Langen Karl-Josef
Published: July 2022

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians’ rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.
Global Prevalence and Risk of Local Recurrence Following Cryosurgery of Giant Cell Tumour of Bone: A Meta-Analysis
Authors: Sumari Shyful Nizam , Mat Zin Nor Azman , Wan Ismail Wan Faisham , Islam Md Asiful
Published: July 2022

The challenge in the surgical treatment of giant cell tumours of bone is the relatively high recurrence rate after curettage alone. The use of a local adjuvant following curettage, on the other hand, has lowered the rate of recurrence. This systematic review and meta-analysis aimed to investigate the prevalence and risk of local recurrence of giant cell tumours of the bone after cryosurgery and the subsequent complications. Web of Science, Scopus, ScienceDirect, PubMed, and Google Scholar were searched to identify articles published until 13 October 2021. A random-effects model was used to examine the pooled prevalence and risk ratio (RR) of local recurrence in patients with giant cell tumours after cryosurgery with 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42020211620). A total of 1376 articles were identified, of which 38 studies (n = 1373, 46.2% male) were included in the meta-analysis. Following cryosurgery, the pooled prevalence of local recurrence in giant cell tumours was estimated as 13.5% [95% CI: 9.3–17.8, I2 = 63%], where European subjects exhibited the highest prevalence (24.2%). Compared to other local adjuvants. The RR of local recurrence following cryosurgery was 0.85 (95% CI: 0.63–1.17, I2 = 15%), which was not statistically significant compared to other local adjuvants. We found 3.9% fracture, 4.0% infection, 2.1% nerve injury, and 1.5% skin necrosis as the common complications. Based on the sensitivity analyses, this study is robust and reliable. This meta-analysis estimated a low prevalence of local recurrence of giant cell tumours with low complications following cryosurgery. Thus, it can be one of the adjuvant options for treating giant cell tumours.
Selective CDK9 Inhibition by Natural Compound Toyocamycin in Cancer Cells
Authors: Pandey Somnath , Djibo Rahinatou , Darracq Anaïs , Calendo Gennaro , Zhang Hanghang , Henry Ryan A. , Andrews Andrew J. , Baylin Stephen B. , Madzo Jozef , Najmanovich Rafael , Issa Jean-Pierre J. , Raynal Noël J.-M.
Published: July 2022

Aberrant transcription in cancer cells involves the silencing of tumor suppressor genes (TSGs) and activation of oncogenes. Transcriptomic changes are associated with epigenomic alterations such as DNA-hypermethylation, histone deacetylation, and chromatin condensation in promoter regions of silenced TSGs. To discover novel drugs that trigger TSG reactivation in cancer cells, we used a GFP-reporter system whose expression is silenced by promoter DNA hypermethylation and histone deacetylation. After screening a natural product drug library, we identified that toyocamycin, an adenosine-analog, induces potent GFP reactivation and loss of clonogenicity in human colon cancer cells. Connectivity-mapping analysis revealed that toyocamycin produces a pharmacological signature mimicking cyclin-dependent kinase (CDK) inhibitors. RNA-sequencing revealed that the toyocamycin transcriptomic signature resembles that of a specific CDK9 inhibitor (HH1). Specific inhibition of RNA Pol II phosphorylation level and kinase assays confirmed that toyocamycin specifically inhibits CDK9 (IC50 = 79 nM) with a greater efficacy than other CDKs (IC50 values between 0.67 and 15 µM). Molecular docking showed that toyocamycin efficiently binds the CDK9 catalytic site in a conformation that differs from other CDKs, explained by the binding contribution of specific amino acids within the catalytic pocket and protein backbone. Altogether, we demonstrated that toyocamycin exhibits specific CDK9 inhibition in cancer cells, highlighting its potential for cancer chemotherapy.
Sonophotocatalysis—Limits and Possibilities for Synergistic Effects
Authors: Paustian Dirk , Franke Marcus , Stelter Michael , Braeutigam Patrick
Published: July 2022

Advanced oxidation processes are promising techniques for water remediation and degradation of micropollutants in aqueous systems. Since single processes such as sonolysis and photocatalysis exhibit limitations, combined AOP systems can enhance degradation efficiency. The present work addresses the synergistic intensification potential of an ultrasound-assisted photocatalysis (sonophotocatalysis) for bisphenol A degradation with a low-frequency sonotrode (f = 20 kHz) in a batch-system. The effects of energy input and suspended photocatalyst dosage (TiO2-nanoparticle, m = 0–0.5 g/L) were investigated. To understand the synergistic effects, the sonication characteristics were investigated by bubble-field analysis, hydrophone measurements, and chemiluminescence of luminol to identify cavitation areas due to the generation of hydroxyl radicals. Comparing the sonophotocatalysis with sonolysis and photocatalysis (incl. mechanical stirring), synergies up to 295% and degradation rates of up to 1.35 min−1 were achieved. Besides the proof of synergistic intensification, the investigation of energy efficiency for a degradation degree of 80% shows that a process optimization can be realized. Thus, it could be demonstrated that there is an effective limit of energy input depending on the TiO2 dosage.
Organic Chemistry and Synthesis Rely More and More upon Catalysts
Authors: Vogel Pierre , Houk Kendall N.
Published: July 2022

A few months before the COVID-19 pandemic, Pierre Vogel and Kendall N. Houk published with a new textbook Wiley-VCH, “Organic Chemistry: Theory, Reactivity, and Mechanisms in Modern Synthesis”, with a foreword from the late Roberts H. Grubbs. The book demonstrates how catalytic processes dominate all fields of modern organic chemistry and synthesis, and how invention combines thermodynamics, kinetics, spectroscopy, quantum mechanics, and thermochemical data libraries. Here, the authors present a few case studies that should be of interest to teachers, practitioners of organic and organometallic chemistry, and the engineers of molecules. The Vogel–Houk book is both textbook and reference manual; it provides a modern way to think about chemical reactivity and a powerful toolbox to inventors of new reactions and new procedures.
Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer
Authors: Bermúdez Miguel A. , Pereira Laura , Fraile Cristina , Valerio Laura , Balboa María A. , Balsinde Jesús
Published: July 2022

In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial β-oxidation of oleic acid. In this review, we discuss the current knowledge of the effects of palmitoleic acid and, where available, sapienic acid and hypogeic acid, on metabolic diseases such as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and cancer. The results have shown diverse effects among studies in cell lines, animal models and humans. Palmitoleic acid was described as a lipokine able to regulate different metabolic processes such as an increase in insulin sensitivity in muscle, β cell proliferation, prevention of endoplasmic reticulum stress and lipogenic activity in white adipocytes. Numerous beneficial effects have been attributed to palmitoleic acid, both in mouse models and in cell lines. However, its role in humans is not fully understood, and is sometimes controversial. Regarding sapienic acid and hypogeic acid, studies on their biological effects are still scarce, but accumulating evidence suggests that they also play important roles in metabolic regulation. The multiplicity of effects reported for palmitoleic acid and the compartmentalized manner in which they often occur, may suggest the overlapping actions of multiple isomers being present at the same or neighboring locations.
Semiconductor-Type Gas Sensors Based on γ-Fe2O3 Nanoparticles and Its Derivatives in Conjunction with SnO2 and Graphene
Authors: Qin Qi , Olimov Diyor , Yin Li
Published: July 2022

The gas sensitivity of semiconductor metal oxides, such as γ-Fe2O3 and SnO2, is investigated together with the synergistic effects in conjunction with grapheme. Nanoparticles of γ-Fe2O3, γ-Fe2O3/SnO2, and γ-Fe2O3/SnO2/RGO, prepared by two-step fabrication, were assembled in gas-sensing devices to assess their sensitivities; response and recovery times for the detection of ethanol, methanol, isopropanol, formaldehyde, H2S, CO, and NO gases at different temperatures but constant concentrations of 100 particles per million (ppm); and H2S, which underwent the dynamic gas sensitivity test in different concentrations. Each sample’s crystallinity and microscopic morphology was investigated with X-ray diffraction and a scanning electron microscope. In comparative gas sensitivity measurements, the ternary composite of γ-Fe2O3/SnO2/RGO was identified as an ideal candidate, as it responds to all four tested liquids in the gas phase as well as H2S with a response value equal to 162.6. Further, only the ternary composite γ-Fe2O3/SnO2/RGO hybrid nanoparticles responded to NO gas with a sensor response value equal to 4.09 in 12 s. However, only the binary composite γ-Fe2O3/SnO2 responded to CO with a corresponding sensitivity of 1.59 units in 7 s.
Oralbiotica/Oralbiotics: The Impact of Oral Microbiota on Dental Health and Demineralization: A Systematic Review of the Literature
Authors: Inchingolo Alessio Danilo , Malcangi Giuseppina , Semjonova Alexandra , Inchingolo Angelo Michele , Patano Assunta , Coloccia Giovanni , Ceci Sabino , Marinelli Grazia , Di Pede Chiara , Ciocia Anna Maria , Mancini Antonio , Palmieri Giulia , Barile Giuseppe , Settanni Vito , De Leonardis Nicole , Rapone Biagio , Piras Fabio , Viapiano Fabio , Cardarelli Filippo , Nucci Ludovica , Bordea Ioana Roxana , Scarano Antonio , Lorusso Felice , Palermo Andrea , Costa Stefania , Tartaglia Gianluca Martino , Corriero Alberto , Brienza Nicola , Di Venere Daniela , Inchingolo Francesco , Dipalma Gianna
Published: July 2022

The oral microbiota plays a vital role in the human microbiome and oral health. Imbalances between microbes and their hosts can lead to oral and systemic disorders such as diabetes or cardiovascular disease. The purpose of this review is to investigate the literature evidence of oral microbiota dysbiosis on oral health and discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis; both have enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches as ORALBIOTICA for oral diseases such as demineralization. PubMed, Web of Science, Google Scholar, Scopus, Cochrane Library, EMBEDDED, Dentistry & Oral Sciences Source via EBSCO, APA PsycINFO, APA PsyArticles, and DRUGS@FDA were searched for publications that matched our topic from January 2017 to 22 April 2022, with an English language constraint using the following Boolean keywords: (“microbio*” and “demineralization*”) AND (“oral microbiota” and “demineralization”). Twenty-two studies were included for qualitative analysis. As seen by the studies included in this review, the balance of the microbiota is unstable and influenced by oral hygiene, the presence of orthodontic devices in the oral cavity and poor eating habits that can modify its composition and behavior in both positive and negative ways, increasing the development of demineralization, caries processes, and periodontal disease. Under conditions of dysbiosis, favored by an acidic environment, the reproduction of specific bacterial strains increases, favoring cariogenic ones such as Bifidobacterium dentium, Bifidobacterium longum, and S. mutans, than S. salivarius and A. viscosus, and increasing of Firmicutes strains to the disadvantage of Bacteroidetes. Microbial balance can be restored by using probiotics and prebiotics to manage and treat oral diseases, as evidenced by mouthwashes or dietary modifications that can influence microbiota balance and prevent or slow disease progression.
When Are Children Most Physically Active? An Analysis of Preschool Age Children’s Physical Activity Levels
Authors: Díaz-Quesada Gema , Gálvez-Calabria María de los Ángeles , Connor Jonathan D. , Torres-Luque Gema
Published: July 2022

The levels of physical activity (PA) in the population have decreased, especially at an early age. The aims of the study were: to evaluate the percentage of children meeting PA recommendations for both genders, and to measure steps and PA level at different time intervals during the week. This was an observational cross-sectional study. Seventy-three schoolchildren (36 boys and 37 girls), aged two years (2.12 ± 0.46), were selected to participate in this study. Participants wore an “Actigraph GT3X” accelerometer for seven days to measure the minutes engaged in moderate-to-vigorous physical activity (MVPA) and step volume. The results show 100% of the children studied met the recommended 60 min/day of MVPA, and 50% achieved 120 min/day MVPA and 13,000 steps per day. No gender differences were found. The results of the analysis show a propensity for higher step volumes and PA values from Monday to Friday. In addition, subjects achieved higher step volumes and PA values during “School Time” than “Out-of-School Time”. Given that during “School Time” children showed higher PA and step values, schools represent an important place to help facilitate PA milestones. This study shows the need for further studies and interventions aimed at understanding and improving children’s PA levels at an early age.
Correlation between BMI and Oral Health Status (DMFT, PI, mSBI, and Salivary 1,5-AG) among the Pediatric Population in Saudi Arabia: A Clinico-Biochemical Study
Authors: Alghamdi Sara Ayid , Aljohar Aziza , Almulhim Basim , Alassaf Abdullah , Bhardwaj Smita Singh , Thomas Julie Toby , Almalki Abdullah , Aljuaid Areej Owaid , Mallineni Sreekanth Kumar
Published: July 2022

The study aimed to investigate the association of varying body mass index (BMI) with oral health status among children aged 5–14 years and correlate the concentration of salivary levels of 1,5-AG with varying BMI, dental caries, and periodontal disease. This cross-sectional study was conducted on subjects aged 5 to 14 years. The children were recruited from the Pediatric Dental Clinic, College of Dentistry, Majmaah University, by convenient sampling method. Sociodemographic details and clinical parameters, including body mass index (BMI), DMFT/def (deciduous decayed tooth (d), deciduous extracted tooth (e), deciduous filled tooth (f), permanent tooth decayed (D), permanent missing tooth (M), and permanent filled tooth (F)), plaque index (PI), and modified sulcular bleeding index (mSBI), were evaluated. Salivary 1,5-anhydroglucitol (1,5-AG) was analyzed using an enzyme-linked immunosorbent assay (ELISA) for all the subjects. Statistical analyses performed using SPSS v. 27 (IBM Statistics, Chicago, IL, USA) and the Kruskal–Wallis and chi-square tests were used for comparisons. The Spearman rank correlation coefficient was used to examine the association between the study subjects’ independent variables, BMI, and caries activity. The mean def score, PI, and mSBI scores were higher in obese children. PI score, mSBI score, and salivary concentrations of 1,5-AG between the BMI categories were statistically significant (p < 0.001). The study emphasizes promoting preventive oral health regimes, health awareness campaigns, and nutritional educational programs among the pediatric population.