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Abstract It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies.

Abstract The tryptophan-metabolizing kynurenine pathway (KP) can be activated by enhanced inflammatory responses and has been implicated in the pathophysiology of schizophrenia. However, there is little evidence for KP dysregulation in the early course of psychotic illness. We aimed to investigate the potential immune-mediated hyperactivity of KP in individuals with first-episode psychosis (FEP) and the relationship with symptom severity and treatment response outcomes. Serum immunoassays were performed to measure peripheral levels of inflammatory cytokines (IL-1β, IL-10, TNF-a), KP rate-limiting enzymes (IDO/TDO), and kynurenic acid (KYNA) metabolite in 104 antipsychotic-naïve patients with FEP and 80 healthy controls (HC). The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF) were administered to assess psychopathology and functioning status at admission and following 4-week treatment with antipsychotics. Cytokine and KP components levels were substantially increased in FEP patients compared to HC, before and after antipsychotic treatment. A significant positive correlation between pro-inflammatory IL-1β and KYNA levels was observed among FEP patients, but not in HC. Importantly, within-patient analysis revealed that those with higher baseline KYNA experienced more severe negative symptoms and poorer clinical improvement at follow-up. These findings suggest that KP is upregulated in early psychosis, likely through the induction of IL-1β-dependent pathways, and raised peripheral KYNA might represent a promising indicator of non-response to antipsychotic medication in patients with FEP.

Abstract Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Abstract Background Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers. Material and methods A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform. Results Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs. Conclusion Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Nanotechnology has seen significant growth in the past few decades, with the use of nanomaterials reaching a wide scale. Given that antimicrobial resistance is peaking, nanotechnology holds distinct potential in this area. This review discusses recent applications of metal and metal oxide nanoparticles as antibacterial, antifungal, and antiviral agents, particularly focusing on their topical applications and their role in chronic wound therapy. We explore their use in various forms, including coated, encapsulated, and incorporated in hydrogels or as complexes, proposing them as topical antimicrobials with promising properties. Some studies have shown that metal and metal oxide nanoparticles can exhibit cytotoxic and genotoxic effects, while others have found no such properties. These effects depend on factors such as nanoparticle size, shape, concentration, and other characteristics. It is essential to establish the dose or concentration associated with potential toxic effects and to investigate the severity of these effects to determine a threshold below which metal or metal oxide nanoparticles will not produce negative outcomes. Therefore, further research should focus on safety assessments, ensuring that metal and metal oxide nanoparticles can be safely used as therapeutics in biomedical sciences.

Background and Objectives: Recent studies have focused on the association between the risk of diabetic retinopathy (DR) and the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene; however, their results remain inconclusive. Thus, a systematic review and meta-analysis were carried out to clarify the role of these polymorphisms in the development of DR. Materials and Methods: A systematic search of electronic databases (PubMed, Scopus, and Cochrane Library) was conducted until 25 June 2024, and a reference list of relevant articles was collected, which explored the association between the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene and the risk of DR. The pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated via random-effects model, and the meta-analysis was implemented by using Review Manager 5.4. Results: In total, 6 out of 182 studies, with 1888 cases (DR) and 2285 controls (without DR), were included in the meta-analysis. A statistically significant association between the rs1501299 polymorphism and the DR risk was recorded in G vs. T in the overall analysis (OR = 0.84, 95% CI = 0.72–0.99, p = 2 = 23%, n = 5 studies). Additionally, the summary results in the subgroup analysis according to the control type were as follows: the DR versus diabetes mellitus (DM) control type revealed a statistically significant association in G vs. T: OR = 0.81, 95% CI = 0.67–0.97, p = 2 = 27%, n = 4 studies; GG vs. GT: OR = 0.72, 95% CI = 0.53–0.98, p = 2 = 49%, n = 4 studies; GG vs. (GT + TT): OR = 0.73, 95% CI = 0.55–0.96, p = 2 = 44%, n = 4 studies. No significant association was observed between the rs2241766 polymorphism and the DR risk. Conclusions: The current meta-analysis supports the association between the rs1501299 polymorphism of the ADIPOQ gene and the DR risk in patients with DM.

Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Rehabilitation of fully or partially edentulous patients with dental implants represents one of the most frequently used surgical procedures. The work of Branemark, who observed that a piece of titanium embedded in rabbit bone became firmly attached and difficult to remove, introduced the concept of osseointegration and revolutionized modern dentistry. Since then, an ever-growing need for improved implant materials towards enhanced material–tissue integration has emerged. There is a strong belief that nanoscale materials will produce a superior generation of implants with high efficiency, low cost, and high volume. The aim of this review is to explore the contribution of nanomaterials in implantology. A variety of nanomaterials have been proposed as potential candidates for implant surface customization. They can have inherent antibacterial properties, provide enhanced conditions for osseointegration, or act as reservoirs for biomolecules and drugs. Titania nanotubes alone or in combination with biological agents or drugs are used for enhanced tissue integration in dental implants. Regarding immunomodulation and in order to avoid implant rejection, titania nanotubes, graphene, and biopolymers have successfully been utilized, sometimes loaded with anti-inflammatory agents and extracellular vesicles. Peri-implantitis prevention can be achieved through the inherent antibacterial properties of metal nanoparticles and chitosan or hybrid coatings bearing antibiotic substances. For improved corrosion resistance various materials have been explored. However, even though these modifications have shown promising results, future research is necessary to assess their clinical behavior in humans and proceed to widespread commercialization.

Pancreatic cancer (PC) ranks as the seventh leading cause of cancer-related deaths, with approximately 500,000 new cases reported in 2020. Existing strategies for early PC detection primarily target individuals at high risk of developing the disease. Nevertheless, there is a pressing need to identify innovative clinical approaches and personalized treatments for effective PC management. This study aimed to explore the dysbiosis signature of the fecal microbiota in PC and potential distinctions between its Intraductal papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC) phenotypes, which could carry diagnostic significance. The study enrolled 33 participants, including 22 diagnosed with PDAC, 11 with IPMN, and 24 healthy controls. Fecal samples were collected and subjected to microbial diversity analysis across various taxonomic levels. The findings revealed elevated abundances of Firmicutes and Proteobacteria in PC patients, whereas healthy controls exhibited higher proportions of Bacteroidota. Both LEfSe and Random Forest analyses indicated the microbiome’s potential to effectively distinguish between PC and healthy control samples but fell short of differentiating between IPMN and PDAC samples. These results contribute to the current understanding of this challenging cancer type and highlight the applications of microbiome research. In essence, the study provides clear evidence of the gut microbiome’s capability to serve as a biomarker for PC detection, emphasizing the steps required for further differentiation among its diverse phenotypes.

The rehabilitation of alveolar bone defects of moderate to severe size is often challenging. Currently, the therapeutic approaches used include, among others, the guided bone regeneration technique combined with various bone grafts. Although these techniques are widely applied, several limitations and complications have been reported such as morbidity, suboptimal graft/membrane resorption rate, low structural integrity, and dimensional stability. Thus, the development of biomimetic scaffolds with tailor-made characteristics that can modulate cell and tissue interaction may be a promising tool. This article presents a critical consideration in scaffold’s design and development while also providing information on various fabrication methods of these nanosystems. Their utilization as delivery systems will also be mentioned.

The wide array of structures and characteristics found in ZnO-based nanostructures offers them a versatile range of uses. Over the past decade, significant attention has been drawn to the possible applications of these materials in the biomedical field, owing to their distinctive electronic, optical, catalytic, and antimicrobial attributes, alongside their exceptional biocompatibility and surface chemistry. With environmental degradation and an aging population contributing to escalating healthcare needs and costs, particularly in developing nations, there’s a growing demand for more effective and affordable biomedical devices with innovative functionalities. This review delves into particular essential facets of different synthetic approaches (chemical and green) that contribute to the production of effective multifunctional nano-ZnO particles for biomedical applications. Outlining the conjugation of ZnO nanoparticles highlights the enhancement of biomedical capacity while lowering toxicity. Additionally, recent progress in the study of ZnO-based nano-biomaterials tailored for biomedical purposes is explored, including biosensing, bioimaging, tissue regeneration, drug delivery, as well as vaccines and immunotherapy. The final section focuses on nano-ZnO particles’ toxicity mechanism with special emphasis to their neurotoxic potential, as well as the primary toxicity pathways, providing an overall review of the up-to-date development and future perspectives of nano-ZnO particles in the biomedicine field.

In recent times, there has been considerable interest among researchers in magnesium oxide (MgO) nanoparticles, due to their excellent biocompatibility, stability, and diverse biomedical uses, such as antimicrobial, antioxidant, anticancer, and antidiabetic properties, as well as tissue engineering, bioimaging, and drug delivery applications. Consequently, the escalating utilization of magnesium oxide nanoparticles in medical contexts necessitates the in-depth exploration of these nanoparticles. Notably, existing literature lacks a comprehensive review of magnesium oxide nanoparticles’ synthesis methods, detailed biomedical applications with mechanisms, and toxicity assessments. Thus, this review aims to bridge this gap by furnishing a comprehensive insight into various synthetic approaches for the development of MgO nanoparticles. Additionally, it elucidates their noteworthy biomedical applications as well as their potential mechanisms of action, alongside summarizing their toxicity profiles. This article also highlights challenges and future prospects for further exploring MgO nanoparticles in the biomedical field. Existing literature indicates that synthesized magnesium oxide nanoparticles demonstrate substantial biocompatibility and display significant antibacterial, antifungal, anticancer, and antioxidant properties. Consequently, this review intends to enhance readers’ comprehension regarding recent advancements in synthesizing MgO nanoparticles through diverse approaches and their promising applications in biomedicine.

Abstract The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P

Introduction Sarcoidosis is a disease that results from a combination of environmental and genetic factors. Its genetic basis however, is yet to be clarified. The purpose of this study is to determine whether single nucleotide polymorphisms (SNPs) of the B-cell activating factor (BAFF) and its receptor (BAFF-R) are associated with sarcoidosis. Material and methods Blood samples from one hundred and seventy-three sarcoidosis patients and one hundred and sixty-four controls were collected. All samples were genotyped for BAFF rs2893321, rs1041569 and rs9514828, and for BAFF-R rs61756766. Results Out of the three BAFF polymorphisms, none genotype had any significant association with sarcoidosis, although the T allele in rs1041569 and rs9514828 was overrepresented in sarcoidosis patients. A marginally significant association with sarcoidosis was found in the case of the CT genotype and T allele of BAFF-R rs61756766. Haplotype analysis of the BAFF polymorphisms was also performed, revealing an overrepresentation of the ATT, GTA and GTT haplotypes in the group of patients with cardiac involvement. Conclusions Taken together, the results of this study suggest a possible relationship between BAFF SNPs, rs1041569 and rs9514828, and BAFF-R SNP rs61756766 with sarcoidosis susceptibility and their potential as biomarkers for the disease.

Several tumor types have been efficiently treated with PARP inhibitors (PARPis), which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancers. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. The aim of the present study was to investigate the association between genomic loss of heterozygosity (gLOH) and alterations in 513 genes with targeted and immuno-oncology therapies in 406 samples using an NGS assay. In addition, the %gLOHs of 24 samples were calculated using the Affymetrix technology in order to compare the results obtained via the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations occurred in 5.17% of the malignancies. The %LOH was highly correlated with alterations in the BRCA1/2 genes, since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p = 0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin’s concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis.

Aquatic habitats cover almost 70% of the Earth, containing several species contributing to marine biodiversity. Marine and aquatic organisms are rich in chemical compounds that can be widely used in biomedicine (dentistry, pharmacy, cosmetology, etc.) as alternative raw biomaterials or in food supplements. Their structural characteristics make them promising candidates for tissue engineering approaches in regenerative medicine. Thus, seaweeds, marine sponges, arthropods, cnidaria, mollusks, and the biomaterials provided by them, such as alginate, vitamins, laminarin, collagen, chitin, chitosan, gelatin, hydroxyapatite, biosilica, etc., are going to be discussed focusing on the biomedical applications of these marine-originated biomaterials. The ultimate goal is to highlight the sustainability of the use of these biomaterials instead of conventional ones, mainly due to the antimicrobial, anti-inflammatory, anti-aging and anticancer effect.

This review study aims to present, in a condensed manner, the significance of the use of crystalline carbon-based nanomaterials in biomedical applications. Crystalline carbon-based nanomaterials, encompassing graphene, graphene oxide, reduced graphene oxide, carbon nanotubes, and graphene quantum dots, have emerged as promising materials for the development of medical devices in various biomedical applications. These materials possess inorganic semiconducting attributes combined with organic π-π stacking features, allowing them to efficiently interact with biomolecules and present enhanced light responses. By harnessing these unique properties, carbon-based nanomaterials offer promising opportunities for future advancements in biomedicine. Recent studies have focused on the development of these nanomaterials for targeted drug delivery, cancer treatment, and biosensors. The conjugation and modification of carbon-based nanomaterials have led to significant advancements in a plethora of therapies and have addressed limitations in preclinical biomedical applications. Furthermore, the wide-ranging therapeutic advantages of carbon nanotubes have been thoroughly examined in the context of biomedical applications.

Background/Aims The measurement of infliximab trough levels (IFX-TLs) in patients with inflammatory bowel disease (IBD) is performed to optimize treatment. However, the association between the development of adverse events (AEs) and IFX-TLs has not been sufficiently studied thus far. To investigate the possible association of IFX-TLs with AEs in Greek patients with IBD receiving maintenance treatment with IFX. Methods A retrospective analysis of the registry data of the Gastroenterology Department of the University Hospital of Heraklion, from IBD patients with at least one available IFX-TL measurement during the years 2016 to 2017 was conducted. AEs reported 4 months before and 4 months after the measured IFX-TLs were recorded. The IFX-TLs of patients with or without AEs were compared. Results Of a total of 83 IBD patients (61 Crohn’s disease [73%]; 52 men [63%]; mean age ± standard deviation, 43.3 ± 16.0 years), 147 measurements of IFX-TLs were available (median 4.69 μg/mL [1.32–9.16]), and 99 AEs (67.3%, 14 severe) were registered. The median IFX-TL of patients with AEs was 5.79 μg/mL (1.36–10.25), higher than the median IFX-TL of patients without AEs (3.40 μg/mL [1.30–5.92]), but the difference was not significant (P=0.97). The presence of infections or dermatologic reactions was not correlated with IFX-TLs. There was no difference in the prevalence of the total AEs (66.7% vs. 73.3%, P=0.77) or in the analysis of AEs by group between patients with IFX-TLs ≥ 15 μg/mL and patients with IFX-TLs < 15 μg/mL. Conclusions IFX-TLs are not significantly associated with the development of AEs in IBD patients receiving maintenance treatment with IFX.

Perinatal tissues, mainly the placenta and umbilical cord, contain a variety of different somatic stem and progenitor cell types, including those of the hematopoietic system, multipotent mesenchymal stromal cells (MSCs), epithelial cells and amnion epithelial cells. Several of these perinatal derivatives (PnDs), as well as their secreted products, have been reported to exert immunomodulatory therapeutic and regenerative functions in a variety of pre-clinical disease models. Following experience with MSCs and their extracellular vesicle (EV) products, successful clinical translation of PnDs will require robust functional assays that are predictive for the relevant therapeutic potency. Using the examples of T cell and monocyte/macrophage assays, we here discuss several assay relevant parameters for assessing the immunomodulatory activities of PnDs. Furthermore, we highlight the need to correlate the in vitro assay results with preclinical or clinical outcomes in order to ensure valid predictions about the in vivo potency of therapeutic PnD cells/products in individual disease settings.

Background and Aim: Canine degenerative myelopathy (CDM) is an adult-onset fatal disorder associated with a point mutation of the superoxide dismutase 1 (SOD1) gene (SOD1:c.118G>A). This study aimed to determine the allele and genotype frequencies of this mutation in a group of Belgian Malinois dogs in Greece. Materials and Methods: Samples (n=72) of whole blood were collected from 72 purebred dogs of the Hellenic Armed Forces; these samples were processed for DNA isolation, polymerase chain reaction, and digestion with the restriction endonuclease AcuI. Sample testing was conducted in compliance with ISO17025 accreditation requirements. Results: The observed relative genotype frequencies were 71% for the homozygous (GG), 25% for the heterozygous (AG), and 4% for the homozygous mutant (AA) alleles. These frequencies were close to those expected, indicating no significant departure from Hardy–Weinberg equilibrium (HWE, p=0.395). The frequency of heterozygous animals indicates that a high risk of developing CDM in forthcoming generations exists in the tested population because mating among carriers would result in 25% AA progeny. The medical record of the group of study animals indicated selection against leishmaniosis, as applied throughout generations by owners and breeders. The potential association of this selection with the HWE status of the study population was discussed. Conclusion: The SOD1:c.118G>A mutation was common in the tested group of dogs; thus, they are suitable for a follow-up investigation on the development and progression of CDM. A case-control study on animals with evidence of sensitivity to infectious myelopathy could provide new insights into disease pathogenesis.

Background: Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects both children and adolescents. Symptoms can significantly affect a child’s growth, development, and quality of life, making early diagnosis and effective management crucial. This study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset. Methods: Nine families with pediatric IBD were recruited, comprising seven drug-naïve Crohn’s disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as twenty-four healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis. Results: We identified patterns of dysbiosis and hallmark microbial taxa among patients who shared ethnic, habitual, and dietary traits with themselves and their families. In addition, we examined the impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection. Conclusions: Our results suggest a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD.

Over the last ten years, there has been a growing interest in metal–organic frameworks (MOFs), which are a unique category of porous materials that combine organic and inorganic components. MOFs have garnered significant attention due to their highly favorable characteristics, such as environmentally friendly nature, enhanced surface area and pore volume, hierarchical arrangements, and adjustable properties, as well as their versatile applications in fields such as chemical engineering, materials science, and the environmental and biomedical sectors. This article centers on examining the advancements in using MOFs for environmental remediation purposes. Additionally, it discusses the latest developments in employing MOFs as potential tools for disease diagnosis and drug delivery across various ailments, including cancer, diabetes, neurological disorders, and ocular diseases. Firstly, a concise overview of MOF evolution and the synthetic techniques employed for creating MOFs are provided, presenting their advantages and limitations. Subsequently, the challenges, potential avenues, and perspectives for future advancements in the utilization of MOFs in the respective application domains are addressed. Lastly, a comprehensive comparison of the materials presently employed in these applications is conducted.

Early-stage, precise disease diagnosis and treatment has been a crucial topic of scientific discussion since time immemorial. When these factors are combined with experience and scientific knowledge, they can benefit not only the patient, but also, by extension, the entire health system. The development of rapidly growing novel technologies allows for accurate diagnosis and treatment of disease. Nanomedicine can contribute to exhaled breath analysis (EBA) for disease diagnosis, providing nanomaterials and improving sensing performance and detection sensitivity. Through EBA, gas-based nano-sensors might be applied for the detection of various essential diseases, since some of their metabolic products are detectable and measurable in the exhaled breath. The design and development of innovative nanomaterial-based sensor devices for the detection of specific biomarkers in breath samples has emerged as a promising research field for the non-invasive accurate diagnosis of several diseases. EBA would be an inexpensive and widely available commercial tool that could also be used as a disease self-test kit. Thus, it could guide patients to the proper specialty, bypassing those expensive tests, resulting, hence, in earlier diagnosis, treatment, and thus a better quality of life. In this review, some of the most prevalent types of sensors used in breath-sample analysis are presented in parallel with the common diseases that might be diagnosed through EBA, highlighting the impact of incorporating new technological achievements in the clinical routine.

In this work, we investigate the complexation behavior of poly(oligo(ethylene glycol)methyl methacrylate)-co-poly(2-(diisopropylamino)ethyl methacrylate), P(OEGMA-co-DIPAEMA), hyperbranched polyelectrolyte copolymers, synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization, with short-linear DNA molecules. The synthesized hyperbranched copolymers (HBC), having a different chemical composition, are prepared in order to study their ability to bind with a linear nucleic acid at various N/P ratios (amine over phosphate groups). Specifically, the three pH and thermo-responsive P(OEGMA-co-DIPAEMA) hyperbranched copolymers were able to form polyplexes with DNA, with dimensions in the nanoscale. Using several physicochemical methods, such as dynamic and electrophoretic light scattering (DLS, ELS), as well as fluorescence spectroscopy (FS), the complexation process and the properties of formed polyplexes were explored in response to physical and chemical stimuli such as temperature, pH, and ionic strength. The mass and the size of polyplexes are shown to be affected by the hydrophobicity of the copolymer utilized each time, as well as the N/P ratio. Additionally, the stability of polyplexes in the presence of serum proteins is found to be excellent. Finally, the multi-responsive hyperbranched copolymers were evaluated regarding their cytotoxicity via in vitro experiments on HEK 293 non-cancerous cell lines and found to be sufficiently non-toxic. Based on our results, these polyplexes could be useful candidates for gene delivery and related biomedical applications.

Abstract Although pancreatic ductal adenocarcinoma (PDAC) survival is poor, there are differences in patients’ response to the treatments. Detection of predictive biomarkers explaining these differences is of the utmost importance. In a recent study two genetic markers (CD44-rs353630 and CHI3L2-rs684559) were reported to be associated with survival after PDAC resection. We attempted to replicate the associations in 1856 PDAC patients (685 resected with stage I/II) from the PANcreatic Disease ReseArch (PANDoRA) consortium. We also analysed the combined effect of the two genotypes in order to compare our results with what was previously reported. Additional stratified analyses considering TNM stage of the disease and whether the patients received surgery were also performed. We observed no statistically significant associations, except for the heterozygous carriers of CD44-rs353630, who were associated with worse OS (HR = 5.01; 95% CI 1.58–15.88; p = 0.006) among patients with stage I disease. This association is in the opposite direction of those reported previously, suggesting that data obtained in such small subgroups are hardly replicable and should be considered cautiously. The two polymorphisms combined did not show any statistically significant association. Our results suggest that the effect of CD44-rs353630 and CHI3L2-rs684559 cannot be generalized to all PDAC patients.

Abstract Background Canine inflammatory bowel disease (IBD) is a group of chronic gastrointestinal (GI) disorders of still largely unknown etiology. Canine IBD diagnosis is time-consuming and costly as other diseases with similar signs should be initially excluded. In human IBD microRNA (miR) expression changes have been reported in GI mucosa and blood. Thus, there is a possibility that miRs may provide insight into disease pathogenesis, diagnosis and even treatment of canine IBD. The aim of this study was to determine the colonic mucosal and serum relative expression of a miRs panel in dogs with large intestinal IBD and healthy control dogs. Results Compared to healthy control dogs, dogs with large intestinal IBD showed significantly increased relative expression of miR-16, miR-21, miR-122 and miR-147 in the colonic mucosa and serum, while the relative expression of miR-185, miR-192 and miR-223 was significantly decreased. Relative expression of miR-146a was significantly increased only in the serum of dogs with large intestinal IBD. Furthermore, serum miR-192 and miR-223 relative expression correlated to disease activity and endoscopic score, respectively. Conclusion Our data suggest the existence of dysregulated miRs expression patterns in canine IBD and support the potential future use of serum miRs as useful noninvasive biomarkers.

The last 18 years have brought an increasing interest in the therapeutic use of perinatal derivatives (PnD). Preclinical studies used to assess the potential of PnD therapy include a broad range of study designs. The COST SPRINT Action (CA17116) aims to provide systematic and comprehensive reviews of preclinical studies for the understanding of the therapeutic potential and mechanisms of PnD in diseases and injuries that benefit from PnD therapy. Here we describe the publication search and data mining, extraction, and synthesis strategies employed to collect and prepare the published data selected for meta-analyses and reviews of the efficacy of PnD therapies for different diseases and injuries. A coordinated effort was made to prepare the data suitable to make statements for the treatment efficacy of the different types of PnD, routes, time points, and frequencies of administration, and the dosage based on clinically relevant effects resulting in clear increase, recovery or amelioration of the specific tissue or organ function. According to recently proposed guidelines, the harmonization of the nomenclature of PnD types will allow for the assessment of the most efficient treatments in various disease models. Experts within the COST SPRINT Action (CA17116), together with external collaborators, are doing the meta-analyses and reviews using the data prepared with the strategies presented here in the relevant disease or research fields. Our final aim is to provide standards to assess the safety and clinical benefit of PnD and to minimize redundancy in the use of animal models following the 3R principles for animal experimentation.

The medical application of nanotechnology in the field of drug delivery has so far exhibited many efforts in treating simple to extremely complicated and life-threatening human conditions, with multiple products already existing in the market. A plethora of innovative drug delivery carriers, using polymers, surfactants and the combination of the above, have been developed and tested pre-clinically, offering great advantages in terms of targeted drug delivery, low toxicity and immune system activation, cellular biomimicry and enhanced pharmacokinetic properties. Furthermore, such artificial systems can be tailor-made with respect to each therapeutic protocol and disease type falling under the scope of personalized medicine. The simultaneous delivery of multiple therapeutic entities of different nature, such as genes and drugs, can be achieved, while novel technologies can offer systems with multiple modalities often combining therapy with diagnosis. In this review, we present prominent, innovative and state-of-the-art scientific efforts on the applications of surfactant-based, polymer-based, and mixed surfactant-polymer nanoparticle drug formulations intended for use in the medical field and in drug delivery. The materials used, formulation steps, nature, properties, physicochemical characteristics, characterization techniques and pharmacokinetic behavior of those systems, are presented extensively in the length of this work. The material presented is focused on research projects that are currently in the developmental, pre-clinical stage.

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p10−3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10−8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

The contemporary lifestyle of the last decade has undeniably caused a tremendous increase in oxidative-stress-inducing environmental sources. This phenomenon is not only connected with the rise of ROS levels in multiple tissues but is also associated with the induction of senescence in different cell types. Several signaling pathways that are associated with the reduction in ROS levels and the regulation of the cell cycle are being activated, so that the organism can battle deleterious effects. Within this context, autophagy plays a significant role. Through autophagy, cells can maintain their homeostasis, as if it were a self-degradation process, which removes the “wounded” molecules from the cells and uses their materials as a substrate for the creation of new useful cell particles. However, the role of autophagy in senescence has both a “dark” and a “bright” side. This review is an attempt to reveal the mechanistic aspects of this dual role. Nanomedicine can play a significant role, providing materials that are able to act by either preventing ROS generation or controllably inducing it, thus functioning as potential therapeutic agents regulating the activation or inhibition of autophagy.

Background: The term “bacterial translocation” (BT) refers to the migration of bacteria or their products from the gastrointestinal tract to tissues located outside it, and may occur after intestinal ischemia-reperfusion injury. The term “endotoxin” is synonymous, and is used interchangeably with the term lipopolysaccharide (LPS). LPS, a component of Gram-negative gut bacteria, is a potent microbial virulence factor, that can trigger production of pro-inflammatory mediators, causing localized and systemic inflammation. The aim of this study is to investigate if neonatal asphyxia provokes BT and an increased concentration of LPS in an animal model of asphyxia in piglets. Methods: Twenty-one (21) newborn male Landrace/Large White piglets, 1–4 days old, were randomly allocated into three groups, Control (A), Asphyxia (B) and Asphyxia-Cardiopulmonary Resuscitation (CPR) (C). All animals were instrumented, anesthetized and underwent hemodynamic monitoring. In Group A, the animals were euthanized. In Group B, the endotracheal tube was occluded to cause asphyxia leading to cardiopulmonary arrest. In Group C, the animals were resuscitated after asphyxia and further monitored for 30′. Bacterial translocation was assessed by the measurement of endotoxin in blood from the portal vein and the aorta, and also by the measurement of endotoxin in mesenteric lymph nodes (MLNs) at euthanasia. The results are given as median (IQR) with LPS concentration in EU/mL. Results: BT was observed in all groups with minimum LPS concentration in the MLN and maximum concentration in the portal vein. LPS levels in the MLNs were higher in the Group B: 6.38 EU/mL (2.69–9.34) compared to the other groups (Group A: 2.1 EU/mL (1.08–2.52), Group C: 1.66 EU/mL (1.51–2.48), p = 0.012). The aorta to MLNs LPS difference (%) was lower in Group B: 0.13% (0.04–1.17), compared to Group A: 5.08% (2.2–10.7), and Group C: 3.42% (1.5–5.1)) (p = 0.042). The same was detected for portal to MLNs LPS difference (%) which was lower in Group B: 0.94% (0.5–3) compared to Group A: 4.9% (4–15), and Group C: 3.85% (1.5–5.1)) (p = 0.044). Conclusions: Neonatal asphyxia can provoke ΒΤ and increased LPS concentration in blood and tissue located outside the gastrointestinal system.

The synthesis of titania-based composite materials with anticancer potential under visible-light irradiation is the aim of this study. In specific, titanium dioxide (TiO2) nanoparticles (NPs) chemically modified with silver were embedded in a stimuli-responsive microgel (a crosslinked interpenetrating network (IP) network that was synthesized by poly (N-Isopropylacrylamide) and linear chains of polyacrylic acid sodium salt, forming composite particles. The ultimate goal of this research, and for our future plans, is to develop a drug-delivery system that uses optical fibers that could efficiently photoactivate NPs, targeting cancer cells. The produced Ag-TiO2 NPs, the microgel and the composite materials were characterized through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), micro-Raman spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM). Our results indicated that Ag-TiO2 NPs were successfully embedded within the thermoresponsive microgel. Either Ag-TiO2 NPs or the composite materials exhibited high photocatalytic degradation efficiency on the pollutant rhodamine B and significant anticancer potential under visible-light irradiation.

Semiconductor photocatalysts, particularly ZnO nanoparticles, were synthesized via the precipitation method using four different precursors (zinc acetate/zinc nitrate/zinc sulfate/zinc chloride) and compared, according to their optical, structural, photocatalytic, and anticancer properties. The materials were characterized via X-ray Diffraction method (XRD), micro-Raman, Fourier Transform Infrared Spectroscopy (FT-IR), Brunauer–Emmett–Teller (BET), Dynamic Light Scattering (DLS), and Field Emission Scanning Electron Microscope (FESEM) analysis. Photocatalysis was conducted under UV and visible light irradiation, using Rhodamine B as the organic pollutant. It was observed that the highest photocatalysis efficiency was obtained by the nanoparticles synthesized from the zinc acetate used as precursor material. A cell-dependent anticancer efficiency of the tested ZnO nanoparticles was also observed, that was also attributed to the different precursors and the synthesis method, revealing that the nanoparticles that were synthesized from zinc acetate were more bioactive among the four tested precursors. Overall, the data revealed that both the enhanced photocatalytic and biological activity of ZnO nanoparticles derived from zinc acetate precursor could be attributed to the reduced crystalline size, increased surface area, as well as the observed hexagonal crystalline morphology.

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.

Background: MicroRNAs have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases.Methods: Ten-week-old male C57Bl/6 mice were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5 mg/kg (Group A, n = 10) or 5 mg/kg microRNA mimic negative control (Group B, n = 10) on days 1, 3, and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR.Results: Following microRNA-126 mimic administration in Group A subjects, we noted a stepwise increase in I/N hind limb perfusion ratio (Day 0: 0.364 ± 0.032 vs. Day 8: 0.788 ± 0.049 vs. Day 28: 0.750 ± 0.039, p = 0.001). In Group B a stepwise increase in I/N hind limb perfusion ratio was observed (Day 0: 0.272 ± 0.057 vs. Day 8: 0.382 ± 0.020 vs. Day 28: 0.542 ± 0.028, p = 0.074). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p < 0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (p < 0.001). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population.Conclusion: MicroRNA-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.

Abstract Background Crohn’s disease (CD) and Ulcerative colitis (UC) are the two main entities of inflammatory bowel disease (IBD). Previous works have identified more than 200 risk factors (including loci and signaling pathways) in populations of predominantly European ancestry. Our study was conducted on an extended population-specific cohort of 573 Greek IBD patients (364 CD and 209 UC) and 445 controls. Aims To highlight the different genetic and functional background of IBD and its phenotypes, utilizing contemporary systems bioinformatics methodologies. Methods Disease-associated SNPs, obtained via our own 89 loci IBD risk GWAS panel, were detected with the whole genome association analysis toolset PLINK. These SNPs were used as input for 2 novel and different pathway analysis methods to detect functional interactions. Specifically, PathwayConnector was used to create complementary networks of interacting pathways whereas; the online database of protein interactions STRING provided protein–protein association networks and their derived pathways. Network analyses metrics were employed to identify proteins with high significance and subsequently to rank the signaling pathways those participate in. Results The reported complementary pathway and enriched protein–protein association networks reveal several novel and well-known key players, in the functional background of IBD like Toll-like receptor, TNF, Jak-STAT, PI3K-Akt, T cell receptor, Apoptosis, MAPK and B cell receptor signaling pathways. IBD subphenotypes are found to have distinct genetic and functional profiles which can contribute to their accurate identification and classification. As a secondary result we identify an extended network of diseases with common molecular background to IBD. Conclusions IBD’s burden on the quality of life of patients and intricate functional background presents us constantly with new challenges. Our data and methodology provide researchers with new insights to a specific population, but also, to possible differentiation markers of disease classification and progression. This work, not only provides new insights into the interplay among IBD risk variants and their related signaling pathways, elucidates the mechanisms underlying IBD and its clinical sequelae, but also, introduces a generalized bioinformatics-based methodology which can be applied to studies of different disorders.

Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan–Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan–Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival.

Inflammatory Bowel Diseases (IBDs) are characterized by chronic relapsing inflammation of the gastrointestinal tract. The mesenchymal stem/stromal cell-derived secretome and secreted extracellular vesicles may offer novel therapeutic opportunities in patients with IBD. Thus, exosomes may be utilized as a novel cell-free approach for IBD therapy. The aim of our study was to examine the possible anti-inflammatory effects of secretome/exosomes on an IBD-relevant, in vitro model of LPS-induced inflammation in human intestinal SubEpithelial MyoFibroblasts (SEMFs). The tested CM (Conditioned Media)/exosomes derived from a specific population of second-trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped amniotic fluid MSCs (SS-AF-MSCs), and specifically, their secreted exosomes could be utilized as a novel cell-free approach for IBD therapy. Therefore, we studied the effect of SS-AF-MSCs CM and exosomes on LPS-induced inflammation in SEMF cells. SS-AF-MSCs CM and exosomes were collected, concentrated, and then delivered into the cell cultures. Administration of both secretome and exosomes derived from SS-AF-MSCs reduced the severity of LPS-induced inflammation. Specifically, IL-1β, IL-6, TNF-α, and TLR-4 mRNA expression was decreased, while the anti-inflammatory IL-10 was elevated. Our results were also verified at the protein level, as secretion of IL-1β was significantly reduced. Overall, our results highlight a cell-free and anti-inflammatory therapeutic agent for potential use in IBD therapy.

Background: Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. Patients and Methods: Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. Results: The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. Conclusions: Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

Rapidly evolving and ever-increasing knowledge of the molecular pathophysiology of pancreatic cancer has leveraged our understanding altogether to a next level. Compared to the exciting ground-breaking discoveries related to underlying mechanisms of pancreatic cancer onset and progression, however, there had been relatively few advances in the therapeutic options available for the treatment. Since the discovery of the DNA structure as a helix which replicates semi-conservatively to pass the genetic material to the progeny, there has been conceptual refinement and continuous addition of missing pieces to complete the landscape of central dogma. Starting from transcription to translation, modern era has witnessed non-coding RNA discovery and central role of these versatile regulators in onset and progression of pancreatic cancer. Long non-coding RNAs (lncRNAs) have been shown to act as competitive endogenous RNAs through sequestration and competitive binding to myriad of microRNAs in different cancers. In this article, we set spotlight on emerging evidence of regulation of different signaling pathways (Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT and NOTCH) by lncRNAs. Conceptual refinements have enabled us to understand how lncRNAs play central role in post-translational modifications of various proteins and how lncRNAs work with epigenetic-associated machinery to transcriptionally regulate gene network in pancreatic cancer.

COVID-19 incidence and case fatality rates (CFR) differ among ethnicities, stimulating efforts to pinpoint genetic factors that could explain these phenomena. In this regard, the multiallelic apolipoprotein E (APOE) gene has recently been interrogated in the UK biobank cohort, demonstrating associations of the APOE ε4/ε4 genotype with COVID-19 severity and mortality. The frequency of the ε4 allele and thus the distribution of APOE ε4/ε4 genotype may differ among populations. We have assessed APOE genotypes in 1638 Greek individuals, based on haplotypes derived from SNP rs7412 and rs429358 and found reduced frequency of ε4/ε4 compared to the British cohort. Herein we discuss this finding in relation to CFR and hypothesize on the potential mechanisms linking APOE ε4/ε4 to severe COVID-19. We postulate that the metabolic deregulation ensued by APOE4, manifested by elevated cholesterol and oxidized lipoprotein levels, may be central to heightened pneumocyte susceptibility to infection and to exaggerated lung inflammation associated with the ε4/ε4 genotype. We also discuss putative dietary and pharmacological approaches for the prevention and management of COVID-19 in APOE ε4/ε4 individuals.

Liposomes with adjuvant properties are utilized to carry biomolecules, such as proteins, that are often sensitive to the stressful conditions of liposomal preparation processes. The aim of the present study is to use the aqueous heat method for the preparation of polymer-grafted hybrid liposomes without any additional technique for size reduction. Towards this scope, liposomes were prepared through the combination of two different lipids with adjuvant properties, namely dimethyldioctadecylammonium (DDA) and D-(+)-trehalose 6,6′-dibehenate (TDB) and the amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PLMA-b-PDMAEMA). For comparison purposes, PAMAM dendrimer generation 4 (PAMAM G4) was also used. Preformulation studies were carried out by differential scanning calorimetry (DSC). The physicochemical characteristics of the prepared hybrid liposomes were evaluated by light scattering and their morphology was evaluated by cryo-TEM. Subsequently, in vitro nanotoxicity studies were performed. Protein-loading studies with bovine serum albumin were carried out to evaluate their encapsulation efficiency. According to the results, PDMAEMA-b-PLMA was successfully incorporated in the lipid bilayer, providing improved physicochemical and morphological characteristics and the ability to carry higher cargos of protein, compared to pure DDA:TDB liposomes, without affecting the biocompatibility profile. In conclusion, the aqueous heat method can be applied in polymer-grafted hybrid liposomes for protein delivery without further size-reduction processes.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from inappropriately high PTH secretion. It usually results from the presence of a single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma. All these conditions require different management, and it is important to be able to differentiate the underlined pathology, in order for the clinicians to provide the best therapeutic approach. Elucidation of the genetic background of each of these clinical entities would be of great interest. However, the molecular factors that control parathyroid tumorigenesis are poorly understood. There are data implicating the existence of specific genetic pathways involved in the emergence of parathyroid tumorigenesis. The main focus of the present study is to present the current optimal diagnostic and management protocols for pHPT as well as to review the literature regarding all molecular and genetic pathways that are to be involved in the pathophysiology of sporadic pHPT.

Abstract Background Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Methods Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Results Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, ΙΙΙ β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. Conclusions ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III β-tubulin was positively correlated with chemotherapy resistance.