bluuebunny/crossref_metadata_2025 huggingface dataset:
Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy
Authors: Demina Polina A. , Khaydukov Kirill V. , Babayeva Gulalek , Varaksa Pavel O. , Atanova Alexandra V. , Stepanov Maxim E. , Nikolaeva Maria E. , Krylov Ivan V. , Evstratova Irina I. , Pokrovsky Vadim S. , Zhigarkov Vyacheslav S. , Akasov Roman A. , Egorova Tatiana V. , Khaydukov Evgeny V. , Generalova Alla N.
Published: June 2023

Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs.
Analysis of MMP-2-735C/T (rs2285053) and MMP-9-1562C/T (rs3918242) Polymorphisms in the Risk Assessment of Developing Lung Cancer
Authors: Wadowska Katarzyna , Błasiak Piotr , Rzechonek Adam , Śliwińska-Mossoń Mariola
Published: June 2023

Matrix metalloproteinase (MMP)-2 and -9 are gelatinases which are capable of degrading type IV collagen and have been linked to cancer invasion and metastatic development. MMP-2 and MMP-9 gene polymorphisms may affect their biological function, and thus their role in cancer development and progression. We analyzed the association of the polymorphism frequencies of MMP-2-735C/T and MMP-9-1562C/T with MMP-2 and MMP-9 serum concentrations, as well as their potential effects in lung cancer patients. We conducted a retrospective, case-control study consisting of 112 lung cancer patients and 100 healthy individuals from a Caucasian population in Poland. Polymerase chain reaction with restriction fragment length polymorphism (PCR/RFLP) and electrophoresis was used to genotype genomic DNA from whole blood samples. MMP-2 and MMP-9 serum concentrations were then determined using ELISA. For statistical analysis, Statistica version 13 from TIBCO Software Inc. was utilized with a significance level <0.05. Logistic regression analysis revealed that MMP-2-735CC (OR = 5.39; 95% CI = 0.62–47.17; p = 0.238504) and -735CT genotype (OR = 7.22; 95% CI = 0.78–67.14; p = 0.072836), as well as MMP-9-1562CC (OR = 1.45; 95% CI = 0.31–6.70; p = 0.757914) and -1562CT genotype (OR = 1.60; 95% CI = 0.33–7.83; p = 0.548801) were associated with a higher risk of lung cancer. There were statistically significant differences observed in the MMP-2 concentration between individuals with the -735CC genotype and the -735CT genotype (non-smoking control: 204.04 ng/mL vs. 237.00 ng/mL, respectively, p = 0.041479; adenocarcinoma patients: 157.69 ng/mL vs. 126.37 ng/mL, respectively, p = 0.013222), as well as differences in the MMP-9 concentration between individuals with the -1562CC genotype and the -1562CT genotype (smoking control: 385.67 ng/mL vs. 562.80 ng/mL, respectively, p = 0.000936; patients with other lung neoplasms: 821.64 ng/mL vs. 928.88 ng/mL, respectively p = 0.023315). The role of MMP-2-735C/T and MMP-9 -1562C/T polymorphisms in an increased risk of lung cancer cannot be dismissed. Specific genotypes affect MMP-2 and MMP-9 concentrations in both lung cancer patients and healthy controls, which may thereby increase lung cancer risk, disease aggressiveness, and patient survival outcomes.
Circulating miRNAs Expression in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Soffritti Irene , Gravelsina Sabine , D’Accolti Maria , Bini Francesca , Mazziga Eleonora , Vilmane Anda , Rasa-Dzelzkaleja Santa , Nora-Krukle Zaiga , Krumina Angelika , Murovska Modra , Caselli Elisabetta
Published: June 2023

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multifactorial disease that causes increasing morbidity worldwide, and many individuals with ME/CFS symptoms remain undiagnosed due to the lack of diagnostic biomarkers. Its etiology is still unknown, but increasing evidence supports a role of herpesviruses (including HHV-6A and HHV-6B) as potential triggers. Interestingly, the infection by these viruses has been reported to impact the expression of microRNAs (miRNAs), short non-coding RNA sequences which have been suggested to be epigenetic factors modulating ME/CFS pathogenic mechanisms. Notably, the presence of circulating miRNAs in plasma has raised the possibility to use them as valuable biomarkers for distinguishing ME/CFS patients from healthy controls. Thus, this study aimed at determining the role of eight miRNAs, which were selected for their previous association with ME/CFS, as potential circulating biomarkers of the disease. Their presence was quantitatively evaluated in plasma from 40 ME/CFS patients and 20 healthy controls by specific Taqman assays, and the results showed that six out of the eight of the selected miRNAs were differently expressed in patients compared to controls; more specifically, five miRNAs were significantly upregulated (miR-127-3p, miR-142-5p, miR-143-3p, miR-150-5p, and miR-448), and one was downmodulated (miR-140-5p). MiRNA levels directly correlated with disease severity, whereas no significant correlations were observed with the plasma levels of seven pro-inflammatory cytokines or with the presence/load of HHV-6A/6B genome, as judged by specific PCR amplification. The results may open the way for further validation of miRNAs as new potential biomarkers in ME/CFS and increase the knowledge of the complex pathways involved in the ME/CFS development.
Inhibition of Plasmid Conjugation in Escherichia coli by Targeting rbsB Gene Using CRISPRi System
Authors: Xiao Yawen , Zhang Yan , Xie Fengjun , Olsen Rikke Heidemann , Shi Lei , Li Lili
Published: June 2023

Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic-resistant genes (ARGs) among human pathogens. The spread of ARGs can be halted or diminished by interfering with the conjugation process. In this study, we explored the possibility of using an rbsB gene as a single target to inhibit plasmid-mediated horizontal gene transfer in Escherichia coli by CRISPR interference (CRISPRi) system. Three single-guide RNAs (sgRNAs) were designed to target the rbsB gene. The transcriptional levels of the rbsB gene, the conjugation-related genes, and the conjugation efficiency in the CRISPRi strain were tested. We further explored the effect of the repressed expression of the rbsB gene on the quorum sensing (QS) system and biofilm formation. The results showed that the constructed CRISPRi system was effective in repressing the transcriptional level of the rbsB gene at a rate of 66.4%. The repressed expression of the rbsB gene resulted in the reduced conjugation rate of RP4 plasmid by 88.7%, which significantly inhibited the expression of the conjugation-related genes (trbBp, trfAp, traF and traJ) and increased the global regulator genes (korA, korB and trbA). The repressed rbsB gene expression reduced the depletion of autoinducer 2 signals (AI-2) by 12.8% and biofilm formation by a rate of 68.2%. The results of this study indicated the rbsB gene could be used as a universal target for the inhibition of conjugation. The constructed conjugative CRISPRi system has the potential to be used in ARG high-risk areas.
Aging Triggers Mitochondrial Dysfunction in Mice
Authors: Rosa Frederico Luis Lima , de Souza Itanna Isis Araujo , Monnerat Gustavo , Campos de Carvalho Antonio Carlos , Maciel Leonardo
Published: June 2023

Direct analysis of isolated mitochondria from old mice enables a better understanding of heart senescence dysfunction. Despite a well-defined senescent phenotype in cardiomyocytes, the mitochondrial state in aged cardiomyocytes is still unclear. Here, we report data about mitochondrial function in old mice. Isolated cardiomyocytes’ mitochondria were obtained by differential centrifugation from old and young mice hearts to perform functional analyses of mitochondrial O2 consumption, transmembrane potential, ROS formation, ATP production, and swelling. Our results show that mitochondria from old mouse hearts have reduced oxygen consumption during the phosphorylative states of complexes I and II. Additionally, these mitochondria produced more ROS and less ATP than those of young hearts. Mitochondria from old hearts also showed a depolarized membrane potential than mitochondria from young hearts and, as expected, a greater electron leak. Our results indicate that mitochondria from senescent cardiomyocytes are less efficient in O2 consumption, generating more ROS and producing less ATP. Furthermore, the phosphorylative state of complexes I and II presents a functional defect, contributing to greater leakage of protons and ROS production that can be harmful to the cell.
Antibacterial Films of Silver Nanoparticles Embedded into Carboxymethylcellulose/Chitosan Multilayers on Nanoporous Silicon: A Layer-by-Layer Assembly Approach Comparing Dip and Spin Coating
Authors: Naveas Nelson , Pulido Ruth , Torres-Costa Vicente , Agulló-Rueda Fernando , Santibáñez Mauricio , Malano Francisco , Recio-Sánchez Gonzalo , Garrido-Miranda Karla A. , Manso-Silván Miguel , Hernández-Montelongo Jacobo
Published: June 2023

The design and engineering of antibacterial materials are key for preventing bacterial adherence and proliferation in biomedical and household instruments. Silver nanoparticles (AgNPs) and chitosan (CHI) are broad-spectrum antibacterial materials with different properties whose combined application is currently under optimization. This study proposes the formation of antibacterial films with AgNPs embedded in carboxymethylcellulose/chitosan multilayers by the layer-by-layer (LbL) method. The films were deposited onto nanoporous silicon (nPSi), an ideal platform for bioengineering applications due to its biocompatibility, biodegradability, and bioresorbability. We focused on two alternative multilayer deposition processes: cyclic dip coating (CDC) and cyclic spin coating (CSC). The physicochemical properties of the films were the subject of microscopic, microstructural, and surface–interface analyses. The antibacterial activity of each film was investigated against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria strains as model microorganisms. According to the findings, the CDC technique produced multilayer films with higher antibacterial activity for both bacteria compared to the CSC method. Bacteria adhesion inhibition was observed from only three cycles. The developed AgNPs–multilayer composite film offers advantageous antibacterial properties for biomedical applications.
Biosynthesis and Characterization of Silver Nanoparticles Produced by Parachlorella kessleri and Cyclotella spp., and the Evaluation of Their Antibacterial Activity
Authors: El Ouardy Khadija , Lbouhmadi Rkia , Attaoui Hind , Mouzaki Mustapha , Mouine Hanane , Lemkhente Zohra , Mir Youssef
Published: June 2023

Green synthesis is one of the fastest and best ways for ecofriendly nanoparticle synthesis. This study aims to investigate the use of the green microalgae Parachlorella kesseleri and Cyclotella spp. for the biological synthesis of silver nanoparticles (AgNPs). This work focuses on optimizing various parameters necessary for the production and stability of AgNPs. The nanoparticle formation was confirmed by UV-Visible analysis, which revealed the surface plasmon resonance band at 420 nm. The characterization of the AgNPs was performed using UV-visible spectroscopy, X-ray diffraction (XRD), scanning electron microscopy coupled with energy dispersive X-ray microanalysis (SEM-EDS), Fourier transform infrared spectroscopy (FTIR), and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The antimicrobial properties of these bioactive AgNPs were also tested, showing excellent antibacterial activity against six bacterial strains, Escherichia coli, multidrug-resistant Escherichia coli, Bacillus clausii, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella typhi. The biosynthesis of AgNPs from living cultures of microalgae has remarkable antibacterial properties. Other studies are underway in our laboratory to clarify the mechanism of the biosynthesis of these nanoparticles, and their action on bacteria.
Microchimerism as Post-Transplant Marker of a Chronic Rejection Process
Authors: Sieńko Jerzy , Kotowski Maciej , Czarnecka Wiktoria , Podkówka Albert , Tejchman Karol , Kotfis Katarzyna , Zeair Samir , Czajkowski Zenon , Skonieczna-Żydecka Karolina
Published: June 2023

The risk of losing a transplanted organ is high, and non-invasive markers to warn of this phenomenon are still being sought. We investigated the impact of post-transplant microchimerism on the function of the transplanted kidney. The study included 100 kidney transplant recipients, mostly women. All transplanted organs were from opposite-sex deceased donors. Microchimerism was assessed using multiplex PCR. Male DNA was detected in all urine samples from female recipients and in 13/56 blood samples from female kidney recipients. Female DNA was found in 31/44 urine samples from male recipients, but in none of the blood samples. Microchimerism in the urine of female recipients correlated positively with blood urea (Rs = 0.45; p = 5.84 × 10−4) and K+ ions (Rs = 0.29; p = 0.03), while microchimerism in the blood of female recipients also correlated positively with blood urea (Rs = 0. 28; p = 0.04), cystatin C (Rs = 0.31; p = 0.02) and the number of incompatible HLA alleles (Rs = 0.42; p = 0.01). A history of DGF was associated with higher urinary donor DNA concentrations in female recipients.: Post-transplant microchimerism may serve as a potential marker of chronic kidney rejection.
Kinetics of Glucoregulatory Peptide Hormones during Hemodialysis with Cellulose Triacetate and Polysulfone Dialyzers in Patients with Diabetes and End-Stage Kidney Disease
Authors: Takao Nobuteru , Maruyama Takashi , Kobayashi Hiroki , Kitai Maki , Yoshida Yoshinori , Takashima Hiroyuki , Abe Masanori
Published: June 2023

The mechanisms behind reported decreases in plasma insulin and glucagon during hemodialysis (HD) are not clear. Here, we investigated these mechanisms during HD treatment and the characteristics of insulin and glucagon removal when using two super high-flux membranes. In an experimental study, clearance, adsorption rates, and reduction rates of insulin and glucagon were investigated when using cellulose triacetate (CTA) and polysulfone (PS) membranes in a closed circuit using bovine blood. In a clinical study, 20 diabetes patients with end-stage kidney disease who were stable on HD were randomly selected for two HD sessions with two different membranes. At 1 h after the initiation of HD, insulin and glucagon clearance were measured, and the reduction rates were also investigated. In the experimental study, the PS membrane showed significantly higher clearance, adsorption rates, and reduction rates of insulin and glucagon compared with the CTA membrane. Although glucagon was detected in the ultrafiltration fluids in both membranes, insulin was absent in the PS membrane. In the clinical study, both membranes showed significant reductions in plasma insulin and glucagon at each time point. The PS membrane showed significantly higher insulin clearance and reduction rates compared with the CTA membrane. The two membranes showed no significant difference in glucagon clearance, but the glucagon reduction rate was significantly higher with the PS membrane. Our findings show that HD with the two super high-flux membranes used removes significant amounts of glucoregulatory peptide hormones from plasma in patients with diabetes and end-stage kidney disease, potentially affecting their glucose metabolism.
Energy Landscapes and Heat Capacity Signatures for Monomers and Dimers of Amyloid-Forming Hexapeptides
Authors: Nicy  , Wales David J.
Published: June 2023

Amyloid formation is a hallmark of various neurodegenerative disorders. In this contribution, energy landscapes are explored for various hexapeptides that are known to form amyloids. Heat capacity (CV) analysis at low temperature for these hexapeptides reveals that the low energy structures contributing to the first heat capacity feature above a threshold temperature exhibit a variety of backbone conformations for amyloid-forming monomers. The corresponding control sequences do not exhibit such structural polymorphism, as diagnosed via end-to-end distance and a dihedral angle defined for the monomer. A similar heat capacity analysis for dimer conformations obtained using basin-hopping global optimisation shows clear features in end-to-end distance versus dihedral correlation plots, where amyloid-forming sequences exhibit a preference for larger end-to-end distances and larger positive dihedrals. These results hold true for sequences taken from tau, amylin, insulin A chain, a de novo designed peptide, and various control sequences. While there is a little overall correlation between the aggregation propensity and the temperature at which the low-temperature CV feature occurs, further analysis suggests that the amyloid-forming sequences exhibit the key CV feature at a lower temperature compared to control sequences derived from the same protein.
Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer
Authors: Gherman Alexandra , Balacescu Loredana , Popa Calin , Cainap Calin , Vlad Catalin , Cainap Simona S. , Balacescu Ovidiu
Published: June 2023

The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4–6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.
Metabolic Adjustment of High Intertidal Alga Pelvetia canaliculata to the Tidal Cycle Includes Oscillations of Soluble Carbohydrates, Phlorotannins, and Citric Acid Content
Authors: Islamova Renata , Yanshin Nikolay , Zamyatkina Elizaveta , Gulk Ekaterina , Zuy Ekaterina , Billig Susan , Birkemeyer Claudia , Tarakhovskaya Elena
Published: June 2023

The brown alga Pelvetia canaliculata is one of the species successfully adapted to intertidal conditions. Inhabiting the high intertidal zone, Pelvetia spends most of its life exposed to air, where it is subjected to desiccation, light, and temperature stresses. However, the physiological and biochemical mechanisms allowing this alga to tolerate such extreme conditions are still largely unknown. The objective of our study is to compare the biochemical composition of Pelvetia during the different phases of the tidal cycle. To our knowledge, this study is the first attempt to draft a detailed biochemical network underneath the complex physiological processes, conferring the successful survival of this organism in the harsh conditions of the high intertidal zone of the polar seas. We considered the tide-induced changes in relative water content, stress markers, titratable acidity, pigment, and phlorotannin content, as well as the low molecular weight metabolite profiles (GC-MS-based approach) in Pelvetia thalli. Thallus desiccation was not accompanied by considerable increase in reactive oxygen species content. Metabolic adjustment of P. canaliculata to emersion included accumulation of soluble carbohydrates, various phenolic compounds, including intracellular phlorotannins, and fatty acids. Changes in titratable acidity accompanied by the oscillations of citric acid content imply that some processes related to the crassulacean acid metabolism (CAM) may be involved in Pelvetia adaptation to the tidal cycle.
Firing of Replication Origins Is Disturbed by a CDK4/6 Inhibitor in a pRb-Independent Manner
Authors: Kim Su-Jung , Maric Chrystelle , Briu Lina-Marie , Fauchereau Fabien , Baldacci Giuseppe , Debatisse Michelle , Koundrioukoff Stéphane , Cadoret Jean-Charles
Published: June 2023

Over the last decade, CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have emerged as promising anticancer drugs. Numerous studies have demonstrated that CDK4/6 inhibitors efficiently block the pRb-E2F pathway and induce cell cycle arrest in pRb-proficient cells. Based on these studies, the inhibitors have been approved by the FDA for treatment of advanced hormonal receptor (HR) positive breast cancers in combination with hormonal therapy. However, some evidence has recently shown unexpected effects of the inhibitors, underlining a need to characterize the effects of CDK4/6 inhibitors beyond pRb. Our study demonstrates how palbociclib impairs origin firing in the DNA replication process in pRb-deficient cell lines. Strikingly, despite the absence of pRb, cells treated with palbociclib synthesize less DNA while showing no cell cycle arrest. Furthermore, this CDK4/6 inhibitor treatment disturbs the temporal program of DNA replication and reduces the density of replication forks. Cells treated with palbociclib show a defect in the loading of the Pre-initiation complex (Pre-IC) proteins on chromatin, indicating a reduced initiation of DNA replication. Our findings highlight hidden effects of palbociclib on the dynamics of DNA replication and of its cytotoxic consequences on cell viability in the absence of pRb. This study provides a potential therapeutic application of palbociclib in combination with other drugs to target genomic instability in pRB-deficient cancers.
A Transcriptome Array-Based Approach Links Proteinuria and Distinct Molecular Signatures to Intrarenal Expression of Type I Interferon IFNA5 in Lupus Nephritis
Authors: Korsten Peter , Tampe Björn
Published: June 2023

In systemic lupus erythematosus (SLE), the relevance of non-hematopoietic sources of type I interferon in human autoimmunity has recently been recognized. Particularly, type I interferon production precedes autoimmunity in early skin lesions related to SLE. However, the relevance of intrarenal type I interferon expression has not been shown in lupus nephritis. From transcriptome array datasets, median-centered log2 mRNA expression levels of IFNα (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, and IFNA21), IFNω (IFNW1), and IFNβ (IFNB1) in lupus nephritis were extracted specifically from microdissected tubulointerstitial (n = 32) and glomerular compartments (n = 32). We found an association between proteinuria and tubulointerstitial expression of type I interferon IFNA5 (p = 0.0142), while all others were not significantly associated. By contrast, no such correlation was observed between proteinuria and any type I interferon expression in the glomerular compartment in lupus nephritis. Interestingly, there was no difference between female and male patients (p = 0.8237) and no association between type I interferon IFNA5 expression and kidney function or lupus nephritis progression. Finally, we identified distinct molecular signatures involved in transcriptional regulation (GLI protein-regulated transcription, IRF7 activation, and HSF1-dependent transactivation) and receptor signaling (BMP signaling and GPCR ligand binding) in association with tubulointerstitial expression of type I interferon IFNA5 in the kidney. In summary, this transcriptome array-based approach links proteinuria to the tubulointerstitial expression of type I interferon IFNA5 in lupus nephritis. Because type I interferon receptor subunit I antagonism has recently been investigated in active SLE, the current study further emphasizes the role of type I interferons in lupus nephritis and might also be of relevance for mechanistic studies.
THSD7A Positivity Predicts Poor Survival and Is Linked to High FAK Expression and FGFR1-Wildtype in Female Patients with Squamous Cell Carcinoma of the Lung
Authors: Flockerzi Fidelis Andrea , Hohneck Johannes , Langer Frank , Bohle Rainer Maria , Stahl Phillip Rolf
Published: June 2023

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors. FAK seems to play an important role in lung cancer and is discussed as a potential therapeutic target. In addition, there is evidence that FAK-dependent signaling pathways might be affected by THSD7A. For that reason, we investigated the role of THSD7A as a potential tumor marker in LSCC and whether THSD7A expression has an impact on the expression level of FAK. A total of 101 LSCCs were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity was associated with poor overall survival in female patients and showed a relation to high FAK expression in this subgroup. To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC.
Liquid Biopsy in Hepatocellular Carcinoma: The Significance of Circulating Tumor Cells in Diagnosis, Prognosis, and Treatment Monitoring
Authors: Shaik Mohammed Rifat , Sagar Prem Raj , Shaik Nishat Anjum , Randhawa Navkiran
Published: June 2023

Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor outcomes when diagnosed at an advanced stage. Current curative treatments are most effective in early-stage HCC, highlighting the importance of early diagnosis and intervention. However, existing diagnostic methods, such as radiological imaging, alpha-fetoprotein (AFP) testing, and biopsy, have limitations that hinder early diagnosis. AFP elevation is absent in a significant portion of tumors, and imaging may have low sensitivity for smaller tumors or in the presence of cirrhosis. Additionally, as our understanding of the molecular pathogenesis of HCC grows, there is an increasing need for molecular information about the tumors. Biopsy, although informative, is invasive and may not always be feasible depending on tumor location. In this context, liquid biopsy technology has emerged as a promising approach for early diagnosis, enabling molecular characterization and genetic profiling of tumors. This technique involves analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-derived exosomes. CTCs are cancer cells shed from the primary tumor or metastatic sites and circulate in the bloodstream. Their presence not only allows for early detection but also provides insights into tumor metastasis and recurrence. By detecting CTCs in peripheral blood, real-time tumor-related information at the DNA, RNA, and protein levels can be obtained. This article provides an overview of CTCs and explores their clinical significance for early detection, prognosis, treatment selection, and monitoring treatment response in HCC, citing relevant literature.
Competition among Flavescence Dorée Phytoplasma Strains in the Experimental Insect Vector Euscelidius variegatus
Authors: Rossi Marika , Galetto Luciana , Bodino Nicola , Beltramo Jessica , Gamalero Silvia , Pegoraro Mattia , Bosco Domenico , Marzachì Cristina
Published: June 2023

Phytoplasmas are plant pathogenic wall-less bacteria transmitted in a persistent propagative manner by hemipteran insects, mainly belonging to the suborder Auchenorrhyncha (Fulgoromorpha and Cicadomorpha). Flavescence dorée (FD) is a quarantine disease of grapevine, causing great damage to European viticulture and associated with phytoplasmas belonging to 16SrV-C (FD-C) and -D (FD-D) subgroups. FD-C and FD-D strains share similar pathogenicity, but mixed infections are rare in nature. To investigate the competition among FDp strains, specimens of the laboratory vector Euscelidius variegatus (Hemiptera: Cicadellidae) were forced to acquire both phytoplasma haplotypes upon feeding on FD-C- and FD-D-infected plants or after the injection of both strains. The pathogen colonization of insect bodies and heads was monitored with multiplex qPCR, and the efficiencies of phytoplasma transmission were estimated. Single infection, irrespective of strain type, was more frequent than expected, indicating that competition among FD strains occurs. Hypotheses of competition for resources and/or host active sites or the direct antibiosis of one strain against the other are discussed, based on the genetic complexity of FDp populations and on the high genome variability of the FD-D strain. As FD management still mainly relies on insecticides against vectors, the characterization of FDp haplotypes and the description of their epidemiology also have practical implications.
The Impact of Bariatric Surgery on Quality of Life in Patients with Obesity
Authors: Soroceanu Radu Petru , Timofte Daniel Vasile , Danila Radu , Timofeiov Sergiu , Livadariu Roxana , Miler Ancuta Andreea , Ciuntu Bogdan Mihnea , Drugus Daniela , Checherita Laura Elisabeta , Drochioi Ilie Cristian , Ciofu Mihai Liviu , Azoicai Doina
Published: June 2023

Obesity has become a widespread health problem influencing people’s health, general well-being, and healthcare costs. It also represents an important risk factor for multiple comorbidities and malignancies. Objectives: the primary objective of this study was to provide notable insights to healthcare professionals regarding the management of patients with obesity, to highlight the effectiveness of bariatric surgical methods in losing excess weight, and to establish the relationship between weight loss and changes in quality of life (QoL). Material and methods: our study evaluated the QoL of 76 patients following bariatric surgery at different postoperative stages using the 36-Item Short Form Survey (SF-36) and The World Health Organization Quality of Life—BREF (WHOQOL-BREF) questionnaires. Results: regarding the type of bariatric procedure performed, out of the 76 respondents, 39.47% underwent gastric bypass surgery (RYGB), 56.57% underwent sleeve gastrectomy (LSG), and only 3.94% underwent single anastomosis duodeno-ileal switch (SADI-S). Pertaining to the SF-36 questionnaire, the lowest average scores were found in the energy/fatigue subscales and in the limitations due to mental health, which remained consistent across surgery types with a significant decrease in the SADI-S group. Concerning the WHOQOL-BREF questionnaire, the lowest mean scores were found in the environment (15.03 ± 2.37) and social relations (16.08 ± 2.22) subscales, whilst the highest average scores were in physical health (16.30 ± 2.03) and mental health (16.57 ± 2.16). Conclusions: the findings revealed that whilst bariatric surgery significantly improved physical health, it resulted in a decrease in mental health scores. Consequently, the study emphasizes the importance of adopting a holistic approach to managing obesity that considers improving both physical and mental health outcomes.
Precision Delivery of Steroids as a Rescue Therapy for Gastrointestinal Graft-versus-Host Disease in Pediatric Stem Cell Transplant Recipients
Authors: Levitte Steven , Ganguly Abantika , Frolik Sophie , Guevara-Tique Alix A. , Patel Shaini , Tadas Ann , Klein Orly , Shyr David , Agarwal-Hashmi Rajni , Beach Lynn , Callard Elizabeth , Weinacht Katja , Bertaina Alice , Thakor Avnesh S.
Published: June 2023

Graft versus host disease (GVHD) is one of the most serious complications following stem cell transplant in children and is a major cause of morbidity and mortality. Corticosteroids remain the mainstay of treatment, and although a majority of children respond to systemic steroids, those refractory to or dependent upon corticosteroids suffer from complications secondary to long-term steroid administration. This problem has prompted consideration of steroid-sparing treatment strategies, although the time to clinical remission can be variable. Intraarterial corticosteroid delivery has been used in adults as a rescue therapy in steroid-resistant patients, but its use in children has been limited. We investigated the feasibility of intraarterial steroid administration into the bowel and/or liver in a cohort of six pediatric patients with acute GVHD. All patients successfully underwent treatment with no serious adverse effects. Five of five (100%) patients with gastrointestinal bleeding due to GVHD had rapid symptom improvement by 48 h, which was durable up to three weeks. Three of four (75%) patients with hepatic GVHD had improved cholestasis following intraarterial steroid administration. Our experience with this small cohort preliminarily demonstrated the feasibility and safety of intraarterial steroid administration in children with acute GVHD. This approach warrants consideration as a rescue therapy in steroid-refractory cases and as a “bridge” therapy for children with severe acute GVHD who are transitioning to steroid-sparing regimens.
Predictive Model for the Non-Invasive Diagnosis of Endometriosis Based on Clinical Parameters
Authors: Konrad Lutz , Fruhmann Berger Lea M. , Maier Veronica , Horné Fabian , Neuheisel Laura M. , Laucks Elisa V. , Riaz Muhammad A. , Oehmke Frank , Meinhold-Heerlein Ivo , Zeppernick Felix
Published: June 2023

Objectives: Are other pain symptoms in addition to dysmenorrhea, dyspareunia, dyschezia, dysuria, and chronic pelvic pain correlated to endometriosis and suitable for a clinical prediction model? Methods: We conducted a prospective study from 2016 to 2022, including a total of 269 women with numerous pain symptoms and other parameters. All women filled out two questionnaires and were examined by palpation and transvaginal ultrasound (TVUS). In cases of suspected deep endometriosis, magnetic resonance imaging (MRI) was performed. After the operation, endometriosis was diagnosed by histological examination. Results: All in all, 30 significant parameters and 6 significant numeric rating scale (NRS) scores associated with endometriosis could be identified: 7 pain adjectives, 8 endometriosis-associated pain symptoms, 5 pain localizations, 6 parameters from the PainDETECT, consumption of analgesics, and allergies. Furthermore, longer pain duration (before, during, and after menstruation) was observed in women with endometriosis compared to women without endometriosis (34.0% vs. 12.3%, respectively). Although no specific pain for endometriosis could be identified for all women, a subgroup with endometriosis reported radiating pain to the thighs/legs in contrast to a lower number of women without endometriosis (33.9% vs. 15.2%, respectively). Furthermore, a subgroup of women with endometriosis suffered from dysuria compared to patients without endometriosis (32.2% vs. 4.3%, respectively). Remarkably, the numbers of significant parameters were significantly higher in women with endometriosis compared to women without endometriosis (14.10 ± 4.2 vs. 7.75 ± 5.8, respectively). A decision tree was developed, resulting in 0.904 sensitivity, 0.750 specificity, 0.874 positive predictive values (PPV), 0.802 negative predictive values (NPV), 28.235 odds ratio (OR), and 4.423 relative risks (RR). The PPV of 0.874 is comparable to the positive prediction of endometriosis by the clinicians of 0.86 (177/205). Conclusions: The presented predictive model will enable a non-invasive diagnosis of endometriosis and can also be used by both patients and clinicians for surveillance of the disease before and after surgery. In cases of positivety, as evaluated by the questionnaire, patients can then seek advice again. Similarly, patients without an operation but with medical therapy can be monitored with the questionnaire.
Adjuvant Transthoracic Negative-Pressure Ventilation in Nonintubated Thoracoscopic Surgery
Authors: Taje Riccardo , Fabbi Eleonora , Sorge Roberto , Elia Stefano , Dauri Mario , Pompeo Eugenio
Published: June 2023

Background: To minimize the risks of barotrauma during nonintubated thoracoscopic-surgery under spontaneous ventilation, we investigated an adjuvant transthoracic negative-pressure ventilation (NPV) method in patients operated on due to severe emphysema or interstitial lung disease. Methods: In this retrospective study, NPV was employed for temporary low oxygen saturation and to achieve end-operative lung re-expansion during nonintubated lung volume reduction surgery (LVRS) for severe emphysema (30 patients, LVRS group) and in the nonintubated wedge resection of undetermined interstitial lung disease (30 patients, wedge-group). The results were compared following 1:1 propensity score matching with equivalent control groups undergoing the same procedures under spontaneous ventilation, with adjuvant positive-pressure ventilation (PPV) performed on-demand through the laryngeal mask. The primary outcomes were changes (preoperative–postoperative value) in the arterial oxygen tension/fraction of the inspired oxygen ratio (ΔPO2/FiO2;) and ΔPaCO2, and lung expansion completeness on a 24 h postoperative chest radiograph (CXR-score, 2: full or 1: incomplete). Results: Intergroup comparisons (NPV vs. PPV) showed no differences in demographic and pulmonary function. NPV could be accomplished in all instances with no conversion to general anesthesia with intubation. In the LVRS group, NPV improved ΔPO2/FiO2 (9.3 ± 16 vs. 25.3 ± 30.5, p = 0.027) and ΔPaCO2 (−2.2 ± 3.15 mmHg vs. 0.03 ± 0.18 mmHg, p = 0.008) with no difference in the CXR score, whereas in the wedge group, both ΔPO2/FiO2 (3.1 ± 8.2 vs. 9.9 ± 13.8, p = 0.035) and the CXR score (1.9 ± 0.3 vs. 1.6 ± 0.5, p = 0.04) were better in the NPV subgroup. There was no mortality and no intergroup difference in morbidity. Conclusions: In this retrospective study, NITS with adjuvant transthoracic NPV resulted in better 24 h oxygenation measures than PPV in both the LVRS and wedge groups, and in better lung expansion according to the CXR score in the wedge group.
A Novel Accelerometry Method to Perioperatively Quantify Essential Tremor Based on Fahn–Tolosa–Marin Criteria
Authors: Smid Annemarie , Pauwels Rik W. J. , Elting Jan Willem J. , Everlo Cheryl S. J. , van Dijk J. Marc C. , Oterdoom D. L. Marinus , van Laar Teus , Tamasi Katalin , van der Stouwe A. M. Madelein , Drost Gea
Published: June 2023

The disease status, progression, and treatment effect of essential tremor (ET) patients are currently assessed with clinical scores, such as the Fahn–Tolosa–Marin Clinical Rating Scale for Tremor (FTM). The use of objective and rater-independent monitoring of tremors may improve clinical care for patients with ET. Therefore, the focus of this study is to develop an objective accelerometry-based method to quantify ET, based on FTM criteria. Thirteen patients with ET and thirteen matched healthy participants underwent FTM tests to rate tremor severity, paired with tri-axial accelerometric measurements at the index fingers. Analogue FTM assessments were performed by four independent raters based on video recordings. Quantitative measures were derived from the accelerometric data, e.g., the area under the curve of power in the 4–8 Hz frequency band (AUCP) and maximal tremor amplitude. As such, accelerometric tremor scores were computed, using thresholds based on healthy measurements and FTM criteria. Agreement between accelerometric and clinical FTM scores was analyzed with Cohen’s kappa coefficient. It was assessed whether there was a relationship between mean FTM scores and the natural logarithm (ln) of the accelerometric outcome measures using linear regression. The agreement between accelerometric and FTM scores was substantial for resting and intention tremor tests (≥72.7%). However, the agreement between accelerometric postural tremor data and clinical FTM ratings (κ = 0.459) was low, although their logarithmic (ln) relationship was substantial (R2 ≥ 0.724). Accelerometric test–retest reliability was good to excellent (ICC ≥ 0.753). This pilot study shows that tremors can be quantified with accelerometry, using healthy thresholds and FTM criteria. The test–retest reliability of the accelerometric tremor scoring algorithm indicates that our low-cost accelerometry-based approach is a promising one. The proposed easy-to-use technology could diminish the rater dependency of FTM scores and enable physicians to monitor ET patients more objectively in clinical, intraoperative, and home settings.
Endovis Nail versus Dynamic Hip Screw for Unstable Pertrochanteric Fractures: A Feasibility Randomised Control Trial including Patients with Cognitive Impairment
Authors: Kleftouris George , Tosounidis Theodoros H. , Panteli Michalis , Gathen Martin , Giannoudis Peter V.
Published: June 2023

A prospective, feasibility, randomised study was performed to compare intramedullary versus extramedullary fixation of unstable pertrochanteric fractures and to assess the feasibility of including patients with dementia. From July 2016 to November 2017, 60 consecutive patients with an unstable pertrochanteric (OTA/AO 31-A2) fracture were randomized to either receive a short cephalomedullary nail (Endovis EBA2, Citieffe) or a dynamic hip screw (DHS, Zimmer Biomet). Primary feasibility measures included randomisation, recruitment, and retention rates. Secondary outcomes included peri-operative parameters, patient-reported outcomes and radiographic outcomes. Patients were followed-up at two, four, and twelve weeks. There was no difference in the randomisation rate between patients with and without cognitive impairment. Significantly more patients without cognitive impairment attended the 12-week follow-up. The overall recruitment rate was 0.9 patients per week. Patients treated with the nail had less pain at 2 weeks and less neck collapse, medialisation, and leg shortening at all time points. The rest of secondary outcomes were similar. Patients with dementia can successfully be enrolled in a randomised trial on hip fractures. Patients treated with the Endovis nail had lower levels of pain at two weeks and better radiographic outcomes.
Aminosteroid RM-581 Decreases Cell Proliferation of All Breast Cancer Molecular Subtypes, Alone and in Combination with Breast Cancer Treatments
Authors: Burguin Anna , Roy Jenny , Ouellette Geneviève , Maltais René , Bherer Juliette , Diorio Caroline , Poirier Donald , Durocher Francine
Published: June 2023

Breast cancer (BC) is a heterogenous disease classified into four molecular subtypes (Luminal A, Luminal B, HER2 and triple-negative (TNBC)) depending on the expression of the estrogen receptor (ER), the progesterone receptor (PR) and the human epidermal receptor 2 (HER2). The development of effective treatments for BC, especially TNBC, remains a challenge. Aminosteroid derivative RM-581 has previously shown an antiproliferative effect in multiple cancers in vitro and in vivo. In this study, we evaluated its effect in BC cell lines representative of BC molecular subtypes, including metastatic TNBC. We found that RM-581 has an antiproliferative effect on all BC molecular subtypes, especially on Luminal A and TNBC, in 2D and 3D cultures. The combination of RM-581 and trastuzumab or trastuzumab-emtansine enhanced the anticancer effect of each drug for HER2-positive BC cell lines, and the combination of RM-581 and taxanes (docetaxel or paclitaxel) improved the antiproliferative effect of RM-581 in TNBC and metastatic TNBC cell lines. We also confirmed that RM-581 is an endoplasmic reticulum (EnR)-stress aggravator by inducing an increase in EnR-stress-induced apoptosis markers such as BIP/GRP78 and CHOP and disrupting lipid homeostasis. This study demonstrates that RM-581 could be effective for the treatment of BC, especially TNBC.
Efficacy and Safety of Low-Dose Protamine in Reducing Bleeding Complications during TAVI: A Propensity-Matched Comparison
Authors: Kneizeh Kinan , Milzi Andrea , Vogt Felix , Witte Klaus , Marx Nikolaus , Lehrke Michael , Almalla Mohammad , Schröder Jörg
Published: June 2023

Objectives: We aimed to evaluate the efficacy and safety of low-dose protamine in reducing access site-related complications during Transcatheter Aortic Valve Implantation (TAVI) as compared to full-dose protamine. Background: Access site-related complications represent an independent predictor of poor outcomes of TAVI. Data regarding heparin reversal with protamine and the dosage needed to prevent bleeding complications are scarce among patients undergoing TAVI. Methods: A total of 897 patients were retrospectively included in the study. Patients who underwent percutaneous coronary intervention within 4 weeks before or concomitantly with TAVI (n = 191) were given 0.5 mg protamine for each 100 units of unfractionated heparin. All other patients (n = 706) were considered as a control group and 1 mg protamine for each 100 units of heparin was administered. Results: The combined intra-hospital endpoint of death, life-threatening major bleeding, and major vascular complications were significantly more frequent in patients receiving low-dose protamine [29 (15.2%) vs. 50 (7.1%), p < 0.001]. After propensity matching (n = 130 for each group) for relevant clinical characteristics including anti-platelet therapy [19 (14.6%) vs. 6 (4.6%), p = 0.006], low-dose protamine predicted the combined endpoint (OR 3.54, 95%-CI 1.36–9.17, p = 0.009), and even in multivariable analysis, low-dose protamine continued to be a predictor of the combined endpoint in the matched model (OR 3.07, 95%-CI 1.17–8.08, p = 0.023) alongside baseline hemoglobin. Conclusions: In this propensity-matched retrospective analysis, a low-dose protamine regime is associated with a higher rate of major adverse events compared to a full-dose protamine regime following transfemoral TAVI.