Reinke9s edema is a smoking-associated, benign, mostly bilateral lesion of the vocal folds leading to difficulties in breathing and voice problems. Pronounced histological changes such as damaged microvessels or immune cell infiltration have been described in the vocal fold connective tissue, the lamina propria. Thus, vocal fold fibroblasts, the main cell type of the lamina propria, have been postulated to play a critical role in disease mediation. Yet information about the pathophysiology is still scarce and treatment is only surgical, i.e. symptomatic. To explore the pathophysiology of Reinke9s edema, we exposed near-primary human vocal fold fibroblasts to medium conditioned with cigarette smoke extract for 24 h as well as 4 days followed by quantitative mass spectrometry. Proteomic analyses after 24 h revealed that cigarette smoke increased proteins previously described to be involved in oxidative stress responses in other contexts. Correspondingly, gene sets linked to metabolism of xenobiotics and reactive oxygen species were significantly enriched among cigarette smoke-induced proteins. Among the proteins most downregulated by cigarette smoke, we identified fibrillar collagens COL1A1 and COL1A2; this reduction was validated by complementary methods. Further, we found a significant increase of UDP-glucose 6-dehydrogenase, generating a building block for biosynthesis of hyaluronan, another crucial component of the vocal fold lamina propria. In line with this result, hyaluronan levels were significantly increased because of cigarette smoke exposure. Long term treatment of 4 days did not lead to significant changes. The current findings corroborate previous studies but also reveal new insights in possible disease mechanisms of Reinke9s edema. We postulate that changes in the composition of the vocal folds9 extracellular matrix -reduction of collagen fibrils, increase of hyaluronan- may lead to the clinical findings. This might ease the identification of better, disease-specific treatment options. Graphical Abstract Highlights First global study on laryngeal cells cultured with cigarette smoke enriched medium. Vocal fold fibroblasts increased production of ECM component hyaluronan. Expression of several fibrillar collagens was reduced.

After the transmission of human viruses through plasma derivatives had been recognized in the early 1980s, virus inactivation and then removal steps have been implemented into their manufacturing processes. These measures have kept plasma derivatives safe ever since and have also served as a barrier against more recently emerging viruses. Given the success of these interventions, they have also been embedded into the manufacturing processes for cell‐derived biological medicinal products. The most effective inactivation process for lipid‐enveloped viruses is treatment by detergents or combinations of solvents and detergents, and thus, these processes have been almost universally adopted. One of the most widely used detergents, Triton X‐100, has recently raised environmental concerns because one of its degradation products possesses hormone‐like (estrogen‐mimetic) activity that may act on wildlife. Consequently, use of the chemical in the European Union will ultimately be prohibited. The current study was conducted to establish an environmentally friendly detergent alternative to Triton X‐100 with fully equivalent efficacy in biotechnological use. A newly synthesized compound, named Nereid, as well as Triton X‐100 reduced, seem to satisfy these requirements, and thus may be suitable replacements for Triton X‐100.

MicroRNAs (miRNAs) are master regulators of drug resistance and have been previously proposed as potential biomarkers for the prediction of therapeutic response in colorectal cancer (CRC). Sorafenib, a multi-kinase inhibitor which has been approved for the treatment of liver, renal and thyroid cancer, is currently being studied as a monotherapy in selected molecular subtypes or in combination with other drugs in metastatic CRC. In this study, we explored sorafenib-induced cellular effects in Kirsten rat sarcoma viral oncogene homolog olog (KRAS) wild-type and KRAS-mutated CRC cell lines (Caco-2 and HRT-18), and finally profiled expression changes of specific miRNAs within the miRNome (>1000 human miRNAs) after exposure to sorafenib. Overall, sorafenib induced a time- and dose-dependent growth-inhibitory effect through S-phase cell cycle arrest in KRAS wild-type and KRAS-mutated CRC cells. In HRT-18 cells, two human miRNAs (hsa-miR-597 and hsa-miR-720) and two small RNAs (SNORD 13 and hsa-miR-3182) were identified as specifically sorafenib-induced. In Caco-2 cells, nine human miRNAs (hsa-miR-3142, hsa-miR-20a, hsa-miR-4301, hsa-miR-1290, hsa-miR-4286, hsa-miR-3182, hsa-miR-3142, hsa-miR-1246 and hsa-miR-720) were identified to be differentially regulated post sorafenib treatment. In conclusion, we confirmed sorafenib as a potential anti-neoplastic treatment strategy for CRC cells by demonstrating a growth-inhibitory and cell cycle–arresting effect of this drug. Changes in the miRNome indicate that some specific miRNAs might be relevant as indicators for sorafenib response, drug resistance and potential targets for combinatorial miRNA-based drug strategies.

Background: Since the beginning of 2024, several European countries reported unusually high numbers of Human parvovirus B19 (B19V) infections. An increase in B19V incidence rate might have implications for blood products for direct transfusion, however, large data sets for analysis of this outbreak are missing.Study Design and Methods: B19V nucleic acid testing (NAT) of plasma donations collected between June 2018 and May 2024 from mainly Central European countries (n = 9.6 million) and the United States (n = 70.7 million) was done to the individual donation level.Results: In Central Europe, there was a marked increase in B19V incidence from November 2023 onwards, which peaked in April 2024 with a 33‐fold higher than average B19V incidence versus before the COVID‐19 pandemic. In the United States, a similar trend was seen, with a yet still 6‐fold lower increase than in Europe at the same time. The largest increase in B19V positivity was seen in the youngest plasma donor cohort.Discussion: A B19V infection gap during the COVID‐19 pandemic is likely the basis for the rebound outbreak in 2023/2024, particularly in Europe. B19V NAT of millions of plasma donations provides for large scale numbers to solidify available epidemiology insight, and to support adequate risk assessments. Based on the situation it may be prudent to consider B19V NAT for blood components specifically directed towards transfusion to higher risk recipients, or alternatively, preselecting B19V seropositive individuals or advanced age donors at higher likelihood of seropositivity and thus lower risk of virus transmission.

SARS-CoV-2 neutralizing antibodies have been suggested to reflect the efficacy of COVID-19 vaccines. This study reports the direct comparison of the SARS-CoV-2 neutralizing antibody response elicited by a protein- (NVX-CoV2373), an mRNA- (Comirnaty), and a vector-based (Vaxzevria) COVID-19 vaccine, calibrated against the WHO international SARS-CoV-2 antibody standard, and further supports the use of neutralizing antibody levels as a correlate of protection.

Over the last three decades, product yields from CHO cells have increased dramatically, yet specific productivity (qP) remains a limiting factor. In a previous study, using repeated cell‐sorting, we have established different host cell subclones that show superior transient qP over their respective parental cell lines (CHO‐K1, CHO‐S). The transcriptome of the resulting six cell lines in different biological states (untransfected, mock transfected, plasmid transfected) was first explored by hierarchical clustering and indicated that gene activity associated with increased qP did not stem from a certain cellular state but seemed to be inherent for a high qP host line. We then performed a novel gene regression analysis identifying drivers for an increase in qP. Genes significantly implicated were first systematically tested for enrichment of GO terms using a Bayesian approach incorporating the hierarchical structure of the GO term tree. Results indicated that specific cellular components such as nucleus, ER, and Golgi are relevant for cellular productivity. This was complemented by targeted GSA that tested functionally homogeneous, manually curated subsets of KEGG pathways known to be involved in transcription, translation, and protein processing. Significantly implicated pathways included mRNA surveillance, proteasome, protein processing in the ER and SNARE interactions in vesicular transport.