Abstract: The complement system include soluble and cell surface proteins and it is an important arm of the innate immune system. Once activated, the complement system rapidly gener-ates proteins with inflammatory and vasoactive activities. Although complement is crucial to host defense and homeostasis, its inappropriate or uncontrolled activation can also drive tissue injury. Glomerulopathy encompasses a spectrum of diseases with diverse eti-ologies, clinical presentations, and outcomes. Among the intricate web of factors contrib-uting to glomerulopathies pathogenesis, the role of complement activation has emerged as a focal point of research interest and therapeutic intervention. The pioneer drug was eculizumab, which made it possible to drastically change the prognosis of atypical hemo-lytic uremic syndrome, an otherwise fatal disease. This comprehensive review aims to elu-cidate the multifaceted interplay between complement pathways and glomerulopathy, shedding light on potential pathway for targeted therapies and improved patient care.

Abstract:

A prospective analysis was conducted to assess the incidence of inflammatory features reported in targeted biopsies of 531 MRI-suspicious lesions with prostate imaging-reporting and data system (PI-RADS) scores of 3 to 5 in 364 men suspected of having PCa. The incidence of inflammatory features in the MRI-suspicious lesions without PCa was 69.6%, compared to 48.1% in those with PCa (p < 0.001). Among the suspicious lesions without PCa, the incidence of inflammatory features ranged from 68.6% to 71.2% across the PI-RADS categories (p = 0.870). Mild chronic prostatitis increased with higher PI-RADS scores, while acute prostatitis decreased, and granulomatous prostatitis was exclusively observed in patients with PI-RADS scores of 4 and 5. The incidence of inflammatory features in the lesions with insignificant PCa (grade group 1) was 66.7%, compared to 42.7% in those with significant PCa (grade group 2 to 5; p = 0.027). The detection of inflammatory features in MRI-suspicious lesions was identified as an independent predictor of a lower likelihood of significant PCa detection, with an odds ratio (OR) of 0.326 (95% CI 0.196-0.541). Mild chronic prostatitis was the only type of prostatitis which was an independent predictor of a lower likelihood of significant PCa, with an OR of 0.398 (95% CI 0.268-0.590). These data suggest that inflammatory features may be considered to be mimickers of significant PCa on MRI.

Abstract: Background: Little is known about the clinical characteristics and pathogens causing hospital-acquired bloodstream infections (HA-BSIs) in relation to an intensive care unit (ICU) stay. Methods: Population-based cohort study, comprising 35% of the Danish population, 2009-2016. We derived four patient groups with first-time HA-BSIs: No ICU stay during the admission (non-ICU patients), HA-BSI acquired before, in, or after an ICU stay (before-ICU, in-ICU, and after-ICU patients). These groups were compared in relation to microbiological and clinical characteristics, including 28- and &gt;28-day mortality. Results: Among 6888 HA-BSI patients, 4017, 792, 1388, and 691 were non-ICU, before-ICU, in-ICU, and after-ICU, respectively. The rates of several microorganisms differed between the patient groups, e.g. Enterococci (9.4% of non-ICU and 32.0% of in-ICU patients). The 28-day mortality was 26.3% in non-ICU, 45.0% in before-ICU, 35.6% in in-ICU, and 19.0% in after-ICU patients. The corresponding adjusted hazard ratios (95% confidence interval) were 2.10 (1.85-2.36), 1.67 (1.50-1.87), and 0.76 (0.63-0.91) (reference: non-ICU patients). There were few differences as regards &gt;28-day mortality. Conclusions: We found large differences between common microorganisms and prognosis between the four patient groups. After-ICU patients had the lowest 28-day mortality despite age and comorbidity characteristics similar to the other three groups.

Abstract: Interstitial cystitis, also referred to as bladder pain syndrome (IC/BPS), is a chronic condition characterized by pain in the bladder and pelvis. The underlying pathogenesis and useful biomarkers still remain unclear. Bioinformatics and Mendelian randomization approaches were utilized to investigate genes associated with IC and identify potential signaling pathways involved. We identified expressed genes (DEGs) using two IC datasets from the Gene Expression Omnibus (GEO) database and used the expression quantitative trait loci (eQTL) and IC genome-wide association studies (GWAS) data for two-sample Mendelian randomization (MR) analysis to determine co-expressed genes. Subsequently, we performed immune cell infiltration and Gene Set Enrichment Analysis (GSEA) analysis to investigate the functional roles and pathways associated with these genes. Lastly, we validated the findings related to the identified co-expressed genes. We identified 447 high-expressed genes and 326 low-expressed genes in IC. Through MR analysis, three significantly co-expressed genes (CD38, FPR1, and SLA) were identified, which exhibited significant positive causal effect on IC. Additionally, elevated levels of activated CD4 memory T cells were observed in the IC patient group, correlating with the three co-expressed genes. Furthermore, these genes are involved in essential biological processes and pathways, including adaptive immune response, immune receptor activity chemokine signaling pathway, cytokine-cytokine receptor interaction, and JAK stat signaling pathway. Finally, we validated the high expression levels of these three genes in an independent cohort. CD38, FPR1, and SLA are promising target genes for the diagnosis and treatment of IC, warranting further research to explore their roles in IC. This strategy has the potential to promote the development of highly specific biomarkers and therapeutic targets, thereby enhancing both diagnostic accuracy and treatment options for IC.

Abstract: The purpose of this communication is to clarify criticisms that have arisen in the context of our publication "Methodological Considerations Regarding the Quantification of DNA Impurities in the COVID-19 mRNA Vaccine Comirnaty®" (Methods Protoc. 2024, 7, 41 [1]). In the meantime, a preprint has appeared entitled "Quantification of objective concentrations of DNA impurities in mRNA vaccines" (Kaiser et al. [2]), which attempts to refute our findings. However, it does not succeed in doing so with the necessary persuasiveness. First of all, it is particularly important that Kaiser et al [2] have confirmed that our results are reproducible when the quantification is carried out using the Qubit® technology in accordance with the manufacturer's instructions, which is exactly what we did. However, it is then claimed by Kaiser et al [2] that the magnitude of the DNA impurities we have shown would be an effect of high amounts of RNA present in the samples. As a proof they quantified a defined concentration of DNA in the presence of very high concentrations of RNA with the Qubit® methodology. However, even the presence of 250 ng/µL RNA resulted only in a comparatively small increase in the DNA value of 0.655 ng/µL and this is far from explaining the DNA concentrations of 12 to 17.8 ng/µL that we have measured in several batches of Comirnaty®. Further, the preprint [2] mentioned that experiments with DNA extracted from the vaccine would show that the very low legal limits for DNA in Comirnaty® are met. However, the authors of this critique have failed to demonstrate that the extractions they performed are indeed quantitative, i.e. reflect the actual DNA contamination. However, based on the related published literature, this must be denied. With this in mind, we can finally confirm that both our methodology and our data, as published in our above-mentioned article [1], imply that DNA impurities as measured with Qubit® by us in Comirnaty® are reliable according to the manufacturer's premises for this DNA quantification technology. In this sense, the DNA values presented in the Kaiser et al. preprint [2] after extraction procedures are obviously artificial effects of the extractions performed and therefore do not represent the true DNA contamination of the concerned Comirnaty® batches.

Abstract: Ovarian cancer remains one of the leading causes of cancer-related deaths in women. There are several processes that are described to have a causal relationship in ovarian cancer development, progression, and metastasis formation, that occur both at the genetic and epigenetic level. One of the mechanisms involved in its pathogenesis and progression is estrogen signaling. Estrogen receptors ERα, ERβ and GPER1, in concert with various coregulators and pioneer transcription factors, mediate the effects of estrogens primarily by transcriptional regulation of estrogen responsive genes, thereby exerting pleiotropic effects including regulation of cellular proliferation and apoptosis. The expression and activity of estrogen receptors and their coregulators have been demonstrated to be regulated by epigenetic mechanisms like histone modifications and DNA methylation. Here, we intend to summarize and to provide an update on the current understanding of epigenetic mechanisms regulating estrogen signaling and their role in ovarian cancer. For this purpose, we reviewed publications on this topic listed in the Pubmed database. Finally, we provide an assessment to which extent drugs acting on the epigenetic level might be suitable for therapy of ovarian cancer.

Abstract: Background: Spinal schwannomas and meningiomas represent common benign tumors of the spinal cord in adults, necessitating total excision. While total laminectomy has conventionally been employed, unilateral hemilaminectomy has emerged as a viable alternative. Methods: A retrospective analysis was conducted on patients undergoing spinal meningioma or schwannoma resection via laminectomy or unilateral hemilaminectomy from January 2013 to January 2023. Patient demographics, operative techniques, and postoperative outcomes were compared. Results: The study comprised 41 patients (mean age: 62.5 ±14.6 years), with 59% schwannomas and 41% meningiomas, predominantly in the thoracic spine. Total excision was achieved in all cases. Schwannoma resections had longer operative times (p=0.001) and greater intraoperative blood loss (p=0.000) compared to meningiomas. Unilateral hemilaminectomy (41%) exhibited ad-vantages over total laminectomy (59%), including reduced postoperative bed rest (p=0.003), shorter hospital stays (p=0.028), and diminished postoperative pain (p=0.02). Conclusions: Uni-lateral hemilaminectomy is a safe and effective approach for spinal schwannomas and menin-giomas of various sizes. It offers superior outcomes compared to total laminectomy, with benefits such as decreased postoperative bed rest, shorter hospitalization, and lower postoperative pain.

Abstract: Abstract: Osteoporosis is a chronic disease that is characterized by a loss of bone density, mainly affecting the microstructure of the bones, due to a decrease in bone mass, thereby making them more fragile and susceptible to fractures. Osteoporosis is currently considered one of the pandemics of the 21st century, affecting around 200 million people. Its most serious consequence is an increased risk of bone fractures, thus making osteoporosis a major cause of disability and even premature death in the elderly. In this review we discuss causes, biochemical mechanisms of bone regeneration, risk factors, pharmacological treatments, prevention and effects of diet, focusing in this case on compounds present in the diet that could have palliative and preventive effects and could be used as concomitant treatments to drugs, which are and should always be the first option. It should be noted as concluding remarks that non-pharmacological treatments such as diet and exercise have, or should have, a relevant role in supporting pharmacology, which is the recommended prescription today, but we cannot ignore that they can have a great relevance in the treatment of this disease.

Abstract: Peanut allergy, a significant public health issue, poses challenges due to its potential for life-threatening anaphylaxis and profound impact on quality of life. Traditional management approaches, including allergen avoidance and epinephrine administration, are effective in mitigating acute symptoms but do not address the underlying allergy or long-term disease burden. Recent advances in immunotherapy, biologics, and innovative technologies such as gene editing and microbiome modulation have introduced promising pathways for desensitization and sustained unresponsiveness. This review provides a comprehensive exploration of emerging therapies for peanut allergy, including oral, sublingual, and epicutaneous immunotherapy, biologic agents, gene-editing techniques, and novel drug therapies. We discuss their mechanisms, clinical efficacy, and associated challenges, emphasizing the potential for these innovations to revolutionize peanut allergy treatment. Despite significant progress, barriers such as adverse reactions, cost, and limited access remain. Addressing these challenges through further research and standardization could transform the future of peanut allergy management.

Abstract: Background: Previously, we confirmed systemic antihypertensive and antioxidant properties of Urtica dioica L. leaf extract (UE) in spontaneously hypertensive rats (SHR). Here, we aimed to evaluate whether UE can alter the NO and Nrf-2 signalling to prevent local oxidative stress and kidney damage in the model of essential hypertension. Methods: SHR were divided into 5 groups: SHRC- control, received 0.5 mL/day of water, SHR+L received 10 mg/kg/day of losartan, SHR+UE10, SHR+UE50, and SHR+UE200 received 10, 50, and 200 mg/kg/day during next 4 weeks. At the end of the experiment, urine samples were collected for albuminuria and nitrate/nitrite assessment. Mean arterial pressure (MAP) was measured, and blood samples were collected for plasma creatinine evaluation. Kidneys were analysed for nitrate/nitrite, oxidative stress, and target molecules by biochemical, Western blot and immunofluorescent techniques. Results: Losartan and UE50 significantly reduced MAP, albuminuria, oxidative stress, fibroinflammatory markers, and NRF-2/CAT/SOD signalling, with a significant increase of 6-nitrotryptophan and eNOS expressions compared to control. The effects of UE showed dose dependence. Conclusions: Beneficial effects of UE and losartan were independent of NRF-2 signalization in SHR. Interestingly, all treatments induced the increase of 6-nitrotryptophan expression, thus further studies are needed to elucidate the mechanisms of such nitrated tryptophan.