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1. Dragu L. D., Chivu-Economescu M., Pitica I. M., Matei L., Bleotu C., Diaconu C. C. and Necula L. G.
Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy, Current issues in molecular biology, Vol 47, Issue 7, 2025 - IF 3.0, doi 10.3390/cimb47070525

Abstract: Immunotherapy has emerged as a promising approach to cancer treatment, but only a small percentage of cancer patients benefit from it. To enhance therapeutic outcomes, it is essential to understand factors influencing immune response and tumor progression. Soluble PD-L1 (sPD-L1) has been identified as an essential element in immune regulation, with potential implications in cancer biology and treatment. This manuscript explores the sources and mechanisms of sPD-L1 production, its role in immune evasion and tumor progression, and its clinical significance. Elevated sPD-L1 levels have been linked to disease severity, survival, and treatment response in various malignancies, and as a consequence, strategies for combinatorial targeting of sPD-L1 with other immunotherapies are considered. Further studies are needed to understand sPD-L1 dynamics and to clarify the mechanisms of sPD-L1-mediated immunosuppression and its therapeutic implications.

2. Dragu L. D., Necula L. G., Bleotu C., Diaconu C. C. and Chivu-Economescu M.
Soluble PD-L1: From Immune Evasion to Cancer Therapy, Life, Vol 15, Issue 4, 2025 - IF 3.4, doi 10.3390/life15040626, PMID: 40283180

3. Neagu A. I., Bostan M , Ionescu V. A., Gheorghe G , Hotnog C. M., Roman V., Mihaila M , Stoica S. I., Diaconu C. C., Diaconu C. C., Ruta S. M. and Bleotu C.
The Impact of the Microbiota on the Immune Response Modulation in Colorectal Cancer, Biomolecules, Vol 15, Issue 7,1005, 2025 - IF 4.8, doi.org/10.3390/ biom15071005, PMID: 40723882

Abstract: Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis—dysbiosis—has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harbouring polyketide synthase (pks) island, and enterotoxigenic Bacteroides fragilis are implicated in CRC through mechanisms involving mucosal inflammation, epithelial barrier disruption, and immune evasion. These pathogens promote pro-tumorigenic inflammation, enhance DNA damage, and suppress effective anti-tumor immunity. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, exert protective effects by preserving epithelial barrier function and priming host immune responses. These beneficial microbes can promote the maturation of dendritic cells, stimulate CD8+ T cell cytotoxicity, and modulate regulatory T cell populations, thereby enhancing anti-tumor immunity. The dichotomous role of the microbiota underscores its potential as both a biomarker and a therapeutic target in CRC. Recent advances in studies have explored microbiota-modulating strategies—ranging from dietary interventions and prebiotics to fe- cal microbiota transplantation (FMT) and microbial consortia—as adjuncts to conventional therapies. Moreover, the composition of the gut microbiome has been shown to influence the responses to immunotherapy and chemotherapy, raising the possibility of microbiome- informed precision oncology therapy. This review synthesizes the current findings on the pathogenic and protective roles of bacteria in CRC and evaluates the translational potential of microbiome-based interventions in shaping future therapeutic paradigms.

4. Chifiriuc M.C., Bleotu C.
Editorial: Common themes in drug resistance: from viruses to humans, Frontiers in Microbiology, Vol. 16, 2025 - IF 4.5, DOI: 10.3389/fmicb.2025.1573798.

5. Radu E., Fertig T.E., Dragu L.D., Pitica I.M., Surleac M., Neagu A.I., Pana L., Pais A., Matei L., Antone-Iordache I., Marta D.S., Peteu V., Nita-Lazar M., Stoica C., Popescu C., Sultana C.M., Botezatu A., Iancu I.V., Chivu-Economescu M., Banica L., Petre A.S., Paraschiv S., Gherghiceanu M., Ruta S.M., Kreuzinger N., Diaconu C.C., Bleotu C.
Monitoring SARS-CoV-2 dissemination in wastewater and virus isolation in cell cultures: An integrated approach for pathogen detection and surveillance. Journal of Cellular and Molecular Medicine Sep 1 2025, 29 - DOI: 10.1111/jcmm.70805

Abstract: Our study presents wastewater (WW) monitoring data, focusing on determining the infectivity of SARS-CoV-2 in the collected samples. Additionally, a panel of different viruses has been tested in the WW samples. The untreated WW monitoring campaign took place over 1 year in Bucharest, with approximately 300 samples being collected twice a week at the wastewater treatment plant (WWTP) and an infectious diseases hospital. Our data indicated that SARS-CoV-2 concentrations in WW preceded the increase in the number of clinical cases by nearly 2 weeks. Differences between locations were notable, with higher raw concentrations in WW samples from the hospital than those from the WWTP. However, after normalising to population equivalent, the hospital samples concentrations dropped significantly, suggesting that WW monitoring at the urban level provides a more complete and epidemiologically relevant picture than data obtained only from hospitals. Only a few isolates could demonstrate SARS-CoV-2 persistence during in vitro passages. Although the success rate was low, the technique remains crucial for validating the viability of viruses. Adenovirus, Bocavirus and Reovirus were the most abundant ones in both urban and hospital wastewater. WW monitoring remains the most effective approach for tracking the dissemination of various pathogens and supporting public health authorities.

6. Hotnog C.M., Bostan M., Anghelescu M., Roman V., Bleotu C., Hainarosie R., Voiosu C., Marineata S., Bostan I.S., Diaconu C.C., Mihaila M.
Long non-coding RNAs: Significant drivers of carcinogenesis mechanisms in head and neck squamous cell carcinoma. Current Issues In Molecular Biology Aug 28 2025, 47 - doi:10.3390/cimb47090698

Abstract: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a complex molecular landscape. Despite extensive research, our understanding of the molecular mechanisms remains incomplete, hindering the development of effective therapeutic strategies for this disease. Long non-coding RNAs (lncRNAs) have emerged as crucial factors in cancer biology, regulating key networks across various malignancies. These molecules exert their regulatory functions through interactions with nucleic acids or proteins, thereby influencing signaling pathways within tumor cells. Consequently, lncRNAs play a significant role in key processes like cell proliferation, metastasis, immune evasion, and treatment resistance. This review offers a comprehensive overview of current knowledge regarding lncRNA-mediated mechanisms in HNSCC. The first section explores how lncRNAs influence tumor processes through various modulation mechanisms, including transcriptional and post-transcriptional regulation, chromatin remodeling, and epigenetic modifications. We also highlight the impact of lncRNAs on specific signaling pathways that control essential cellular functions (e.g., proliferation, apoptosis, angiogenesis, invasion, metastasis). Ultimately, this underscores the promising potential of lncRNAs as diagnostic biomarkers and therapeutic targets capable of enhancing patient care in oncology. Gaining a deep understanding of how lncRNAs modulate carcinogenic mechanisms may yield innovative approaches for early detection, personalized treatment, and improved clinical outcomes for HNSCC patients.

7. Matei L., Chivu-Economescu M., Dragu L.D., Grancea C., Bleotu C., Hrisca R., Popescu C.P., Diaconu C.C., Ruta S.M.
Long-term durability and variant-specific modulation of SARS-CoV-2 humoral and cellular immunity over two years. International Journal of Molecular Sciences Aug 21 2025, 26 - doi:10.3390/ijms26168106

Abstract: There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory—both humoral and cellular—particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, over two years after infection and/or vaccination. The study involved assessing anti-spike IgG and IgA levels over time and analyzing their relationship with neutralizing activity against both ancestral and Omicron SARS-CoV-2 variants. Persistence of T cell responses was evaluated using intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays. Anti-S IgG levels remained stable over time and increased after each immune stimulation, suggesting cumulative immune memory. Neutralizing capacity correlated strongly with IgG levels, showing long-term stability for pre-Omicron variants, but a moderate decline for Omicron. CD4⁺ and CD8⁺ T cell responses persisted across all groups, largely unaffected by Omicron mutations. However, cytokine profiles revealed subtle, variant-dependent changes. These findings underscore the durability of cellular immunity and the comparatively reduced robustness of Omicron-specific humoral responses. Such insights are crucial for understanding long-term protection against evolving SARS-CoV-2 variants and guiding public health strategies.

8. Ionescu, V.A.; Gheorghe, G.; Bleotu, C.; Puiu, L.; Mambet, C.; Diaconu, C.C.; Diaconu, C.C.
Circulating miRNAs as Non-Invasive Biomarkers in Pancreatic Cancer: A Two-Phase Plasma-Based Study. J. Clin. Med. 2025, 14, 6430 - https://doi.org/10.3390/jcm14186430

Abstract: Background/Objectives: MiRNAs have demonstrated promising roles in the diagnosis of pancreatic cancer and in the prognostic assessment of affected patients. Methods: We conducted a prospective pilot study including 23 patients diagnosed with advanced-stage pancreatic cancer and 10 healthy controls, matched by age and sex. In the screening phase, we evaluated the expression of 176 miRNAs in pooled plasma samples from both groups using real-time PCR. Subsequently, we validated the overexpression of selected miRNAs in individual plasma samples using the same technique. Statistical analysis was performed using IBM SPSS Statistics version 29. Results: During the screening phase, 22 miRNAs exhibited differential expression in patients with pancreatic cancer compared to healthy controls. Among these, hsa-miR-100-5p (27.8-fold increase), hsa-miR-122-5p (7.5-fold), hsa-miR-885-5p (7.2-fold), hsa-miR-34a-5p (5.7-fold), and hsa-miR-193a-5p (4.4-fold) showed the most pronounced upregulation. In the validation phase, all five candidates demonstrated significant overexpression in individual plasma samples (p < 0.001). Their circulating levels also showed associations with tumor stage (p < 0.05). Conclusions: Our findings highlight a distinct circulating miRNA signature associated with advanced pancreatic cancer, supporting the potential role of hsa-miR-100-5p, hsa-miR-122-5p, hsa-miR-885-5p, hsa-miR-34a-5p, and hsa-miR-193a-5p as minimally invasive biomarkers for disease detection and staging. Larger, multicenter studies including early-stage patients and disease control groups will be required to validate these biomarkers and determine their clinical utility.

9. Albulescu, A.; Fudulu, A.; Mihaila, M.A.; Iancu, I.; Plesa, A.; Bostan, M.; Botezatu, A.; Brasoveanu, L.I.; Hotnog, C.M.
Epigenetic Remodeling in Thyroid Cancer: New Dimensions of Targeted Therapy Through lncRNA Modulation. Curr. Issues Mol. Biol. 2025, 47, 863 - https://doi.org/10.3390/cimb47100863

Abstract: Thyroid carcinomas are phenotypically heterogeneous malignancies. Advances in molecular and cellular technologies have revealed genetic, epigenetic, and nongenetic factors underlying this heterogeneity. Our study aimed to assess the impact of single and combined treatments with anticancer agents (Carboplatin, Doxorubicin, Paclitaxel, Avastin), natural compounds (Quercetin), and epigenetic modulators (suberoylanilide hydroxamic acid and 5-Azacytidine) on the expression of long noncoding RNAs, methylation regulators, and functional features in the human thyroid cancer cell line K1. Methods: Treated and untreated K1 cells were used throughout experiments to evaluate the drug-induced cytotoxicity, apoptosis, cell cycle distribution, cytokine release, gene expression, and global DNA methylation levels. Results: Some single- and combined-drug treatments modulated both cell cycle progression and apoptotic events, demonstrating anti-tumor activity of the tested compounds. Gene expression analysis showed treatment-specific regulation of target genes and lncRNAs, including both upregulation and downregulation across different drug combinations. All treatments resulted in increased global DNA methylation levels compared to the untreated controls. Several combinations significantly upregulated DNMT1 and DNMT3B, while concomitantly decreased EZH2 levels. Conclusions: These coordinated epigenetic changes highlight the therapeutic potential of combining epigenetic modulators with chemotherapeutic agents, suggesting a strategy to prevent or reverse treatment resistance and improve outcomes in thyroid cancer patients.

10. Micu, A., Diaconescu, A., Minciuna, CE. et al.
Overcoming the Challenge: A Comprehensive Review of Neoadjuvant Treatment Resistance in Rectal Cancer. J Gastrointest Canc 56, 205 (2025) - https://doi.org/10.1007/s12029-025-01324-7

Abstract: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and remains a leading cause of cancer-related mortality, particularly among younger men. Approximately one-third of colorectal cancers occur in the rectum. For patients with locally advanced rectal cancer, neoadjuvant therapy is considered the standard treatment approach. Despite advances in therapeutic approaches, improvements in the 5-year survival rate have been modest. Accurate assessment of tumor response to neoadjuvant therapy (NAT) is critical for guiding subsequent treatment strategies, especially when considering eligibility for non-operative management (NOM). Common evaluation methods include digital rectal examination (DRE), magnetic resonance imaging (MRI), and high-definition flexible endoscopy (HDFE). Tumor regression grading (TRG) systems—both histopathological (pTRG) and MRI-based (mrTRG)—are valuable tools for quantifying treatment response and predicting long-term outcomes. However, resistance to NAT remains a significant clinical challenge and is driven by a complex interplay of molecular mechanisms. Genetic factors, such as RAS mutations, have been linked to resistance to chemoradiotherapy (CRT), while tumors exhibiting microsatellite instability (MSI-high) tend to respond poorly to CRT but may show favorable outcomes with immune checkpoint inhibitors. Epigenetic pathways, including dysregulation of Wnt/β-catenin and PI3K/AKT signaling, along with alterations in DNA damage repair mechanisms, further influence CRT sensitivity. The tumor microenvironment also plays a pivotal role in modulating therapy response. Elements such as immune cell infiltration, hypoxia, angiogenesis, and the presence of cancer-associated fibroblasts (CAFs) contribute to a pro-resistance landscape. Moreover, emerging evidence suggests that gut microbiota composition—particularly an enrichment of Bacteroides species—is associated with diminished response to NAT. Understanding these multifaceted biological interactions is essential for developing personalized and more effective therapeutic strategies, with the goal of enhancing response to NAT and ultimately improving clinical outcomes in patients with rectal cancer.

11. Mitache, M.M., Pîndaru, A., Barbu, I.C. et al.
Comprehensive evaluation of the bactericidal and anti-pathogenic efficacy of chemical disinfectants against antibiotic resistant ESKAPE clinical strains. - BMC Microbiol 25, 592 (2025). https://doi.org/10.1186/s12866-025-04273-0

Abstract: The persistence of nosocomial pathogens in healthcare settings represents a challenge for cleaning and disinfection. Few studies have addressed the efficacy of chemical disinfectants against emergent and multidrug (MDR) resistant ESKAPE bacteria. The aim of this study was to quantify the in-use and off-label efficacy of three commercially available disinfectants: hydrogen-peroxide-, alcohol- and chlorine-based formulations — against twelve genomically characterized ESKAPE pathogens(ST101/258 Klebsiella pneumoniae, ST2 Acinetobacter baumannii, ST131/62 Escherichia coli, ST357 Pseudomonas aeruginosa, ST1 MRSA and ST612/203 vanA-positive Enterococcus faecium) plus four reference strains, and to determine how sub-lethal exposures influence key virulence traits. Disinfectant activity (log₁₀-reduction, LR) was measured by a quantitative suspension test (EN14885) with and without 3% bovine serum albumin. Additional assays simulated real-life use (contaminated nitrile/latex gloves), early biofilm formation (crystal-violet microplate assay) and evaluated the secretion of proteases, phospholipases, lipases and haemolysins. Statistical significance was assessed by one-way ANOVA or unpaired t-tests (P ≤ 0.05). All disinfectants achieved ≥ 5 LR at the manufacturer-specified concentration and contact time; however, efficacy dropped markedly when contact time was halved or concentration reduced. The hydrogen-peroxide-based disinfectant demonstrated minor differences in efficacy. Specifically, the clinical E. faecium 16 VRE strain exhibited higher MBCs compared to the reference strain (3-fold increase) (P < 0.05). A similar behavior was noticed for both clinical Pseudomonas strains that had 4-fold higher MBCs, compared to the P. aeruginosa reference strain (P < 0.05) at a 5-minute contact time. Organic soiling significantly impaired hydrogen peroxide- and chlorine-based disinfectants' activity. On artificially contaminated gloves, the label-strength alcohol-based disinfectant eradicated all strains after 60 s, whereas 30 s exposure or ≥ 25% dilution permitted recovery of up to 10⁵ CFU cm⁻². Sub-inhibitory chlorine or peroxide concentrations reduced early biofilm biomass by 40–70% (P < 0.05) and suppressed extracellular protease/phospholipase activity, while equivalent alcohol exposure had no effect. Manufacturer-recommended concentration and contact time are critical for reliable killing of MDR ESKAPE pathogens. Shortened contact or dilution—common in clinical practice—creates a survival window and may differentially select tolerant species. Chlorine and peroxide formulations additionally attenuate biofilm initiation and soluble virulence factors, suggesting a dual antimicrobial/anti-pathogenic benefit. These findings support strict compliance with label instructions and encourage formulation optimization that couples rapid killing with anti-virulence activity.

12. Adelina-Gabriela Niculescu, Andrei-Mihai Dumitrascu, Anıl Tevfik Koçer, Pelin Pelit Arayıcı, Selcen Arı Yuka, Sinem Koçer, Cem Bülent Üstündağ, Alexandru Mihai Grumezescu, Corneliu Ovidiu Vrancianu, Mara Madalina Mihai, Mihaela Paun, Mariana Carmen Chifiriuc.
Nanotechnology-driven enhancement and modulation of immune responses in monkeypox and respiratory syncytial virus nanovaccine research. Colloids and Surfaces B: Biointerfaces, Volume 254,2025,114829,ISSN 0927-7765 - https://doi.org/10.1016/j.colsurfb.2025.114829

Abstract: The global health landscape continues to face significant challenges from emerging and re-emerging viral pathogens, notably Monkeypox virus (MPXV) and Respiratory Syncytial Virus (RSV). Traditional vaccine approaches often fall short in providing robust and long-lasting immunity against these evolving threats. Nanotechnology offers transformative potential in this regard, enabling precise modulation and enhancement of immune responses through innovative nanovaccine platforms. This review delves into the latest advancements in nanotechnology-driven vaccine research targeting MPXV and RSV, focusing on the unique capabilities of nanoparticles (NPs) to optimize antigen delivery, stabilize vaccine formulations, and modulate immune responses. For MPXV, promising approaches include mRNA-lipid nanoparticles, antigen-conjugated nanoscaffolds, and virosome- or liposome-based nanovaccines, each demonstrating enhanced antigen stability and potent immunogenicity in preclinical models. RSV nanovaccine development leverages diverse nanoplatforms, such as nanocages, virus-like particles, elastin-like polypeptides, mRNA-lipid NPs, and self-aggregating lipopeptides, enabling precise antigen presentation and robust mucosal and systemic immunity. We highlight how these nanoparticle-based vaccines mimic viral structures, facilitating targeted interactions with antigen-presenting cells, optimizing antigen presentation, and promoting strong cellular and humoral immune responses. Despite these advances, clinical translation remains a challenge, with no approved MPXV or RSV nanovaccines currently available. Critical barriers include the need for further characterization of NP safety and immunogenicity, scalable manufacturing, and the identification of key viral antigens for effective targeting. This review underscores the immense potential of nanotechnology to revolutionize vaccine development against MPXV and RSV, offering insights into current challenges and future directions for the field. The integration of nanotechnology in vaccine research holds promise for more effective, durable, and accessible prophylactic solutions, addressing urgent global health needs.

13. Pîndaru A, Măruțescu LG, Popa M, Lambert C, Chifiriuc MC.
Label-Free Flow Cytometry: A Powerful Tool to Rapidly and Accurately Assess the Efficacy of Chemical Disinfectants. Microorganisms. 2025 May 19;13(5):1156 - doi: 10.3390/microorganisms13051156. PMID: 40431327; PMCID: PMC12114458

Abstract: A rapid and accurate evaluation of a chemical disinfectant’s bactericidal efficacy is crucial for ensuring effective infection control, preventing the spread of pathogens, and supporting the development of new disinfectant formulations. In this study, we report a rapid, label-free flow cytometry (FCM) protocol for evaluating the bactericidal efficacy of disinfectants. Five commercial disinfectants (alcohols, oxidizing agents, and alkylating agents) were evaluated against type strains recommended by EN 13727+A2 and ten clinical strains. The label-free FCM method allowed the determination of disinfectant efficacy through assessment of scatter light profiles (FSC-H/SSC-H) and count differences. The label-free FCM provided the results in approximately 4 h and showed strong correlation with standard tests (91.4%, sensitivity 0.94 and specificity 0.98) that can take up to 48 h. Our results represent a proof-of-principle that label-free FCM can reliably assess the efficacy of chemical disinfectants, the same day, and substantially faster than the current growth-based methods. Additionally, the study highlights the potential of the FCM method for detecting the occurrence of viable but non-culturable bacteria following treatment with chlorine-based disinfectants. With its speed, accuracy, and capability to identify bacterial injuries at a single-cell level, the FCM method is a powerful tool for assessing the efficacy of new disinfectant formulations.

14. Mărutescu L, Enea A, Antoniadis NM, Neculae M, Costea DA, Popa M, Dragu E, Codrici E, Ristoiu V, Galateanu B, Hudita A, Gradisteanu Pircalabioru G, Filali-Mouhim A, Vifor Gabriel Bertesteanu S, Lazăr V, Chifiriuc C, Grigore R, Ancuta P.
Humoral and Cellular Immune Responses to SARS-CoV-2 in Participants with Head and Neck Cancer. Viruses. 2025 Jun 13;17(6):848 - doi: 10.3390/v17060848. PMID: 40573439; PMCID: PMC12197323

Abstract: Background: SARS-CoV-2 immunity is understudied in cancer patients. Here, we monitored natural/vaccine-induced SARS-CoV-2 immunity in patients with head and neck cancer (HNC) stratified as vaccinated (mRNA/adenovirus-based vaccines), convalescent, and hybrid immunity. Methods: Plasma/PBMC samples were collected from 49 patients with HNC and 14 non-oncologic controls recruited between August 2021 and March 2022. Longitudinal follow-up was performed on 25 HNC patients. Plasma antibodies (Abs) against Spike (S1/S2), receptor-binding domain (RBD), and nucleocapsid (NC) of IgG/IgA isotypes and 25 cytokines/chemokines were quantified using MILLIPLEX® technology. The frequency, phenotype, and isotype of circulating SARS-CoV-2-specific B-cells were studied by flow cytometry using RBD tetramers (Tet++). The proliferation of B-cells and CD4+ and CD8+ T-cells in response to Spike/NC peptides was monitored by a carboxyfluorescein succinimidyl ester (CFSE) assay. Results: Plasma SARS-CoV-2 S1/S2/RBD IgG/IgA Abs were detected in all HNC participants at enrollment median time since immunization (TSI) 117 days at levels similar to controls and were significantly higher in convalescent/hybrid versus vaccinated. NC IgG/IgA Abs were only detected after infection. The frequency of Tet++ B-cells, enriched in the CD27+ memory phenotype and IgG/IgA isotype, positively correlated with plasma levels of RBD IgG/IgA Abs and Spike-specific CD4+ T-cell proliferation, regardless of the immunization status and TSI. Spike/NC-specific B-cell proliferation reached the highest levels in convalescent HNC and was positively correlated with NC IgG Abs, but not with the frequency of Tet++ B-cells. Finally, Tet++ B-cell frequencies remained stable between the two subsequent visits (median TSI: 117 versus 341 days), indicating their ability to persist for a relatively long time. Conclusions: This study monitored SARS-CoV-2 humoral/cellular immunity in an HNC cohort relative to non-oncologic participants and demonstrates that SARS-CoV-2-specific B-cells persist beyond 11 months post-immunization. These findings have implications for the management of HNC in the context of SARS-CoV-2 infection and other viral infections.

15. Marian Constantin, Ilda Barbu, Corneliu Ovidiu Vrancianu, Mariana Carmen Chifiriuc, Ioana-Mădălina Pitică, Alina Casangiu, Simona Maria Ruță, Coralia Bleotu
Retroviral Remnants in the Human Genome: Classification, Integration and Regulation - https://doi.org/10.1007/s40291-025-00823-4

Abstract: Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections constituting nearly 8% of the human genome. Far from being inert genetic fossils, HERVs have co-evolved with their hosts, acquiring regulatory and functional roles that influence development, immunity and disease. In this comprehensive review, we examine the origin, evolutionary dynamics and structural diversity of HERVs, emphasising their integration, genomic organisation and mosaic recombination patterns. We further highlight how epigenetic modifications, intracellular factors such as transcriptional regulators, hormones and cytokines, and environmental influences regulate HERV expression. By synthesising current evidence linking HERV activity to immune modulation, tumourigenesis, autoimmunity and neurodegenerative processes, we provide an integrated perspective on their dual role as drivers of pathology and contributors to normal physiology. Our analysis underscores that HERVs are not only markers of past infections but also active genomic elements with potential clinical implications, from biomarker discovery to novel therapeutic targets, making their systematic investigation timely and highly relevant.

16. Simona Visan, Loredana Balacescu, Flaviu Drigla, Ovidiu Balacescu, Adela Pintea
Gene Expression Profiles Modulated by Lipophilic Sea Buckthorn (Hippophae rhamnoides L.) Extract in BT-549 Triple-Negative Breast Cancer Cells - PMID: 41409192 PMCID: PMC12706652 DOI: 10.1002/fsn3.71112

Abstract: Triple-negative breast cancer (TNBC) is an aggressive subtype with high heterogeneity, metastasis, and drug resistance, underscoring the need for new therapeutic strategies. Sea buckthorn berries, long used in traditional medicine, are rich in carotenoids with reported anticancer activity. To investigate their transcriptional effects, we treated BT-549 TNBC cells with a saponified lipophilic sea buckthorn berry extract (LSBE) and performed gene expression profiling using microarray (four independent replicates of treated, respectively, untreated cells). LSBE altered the expression of 330 protein-coding genes (111 downregulated, 219 upregulated; fold ratio ±1.5, adj. p < 0.05). ingenuity pathway analysis (IPA) revealed activation of cholesterol biosynthesis (z = 3.46, p = 2.7E−15) and ferroptosis (z = 0.78, p = 5.3E−09), while oxidative stress (z = −2.18, p = 3.4E−05) and cholesterol accumulation (z = −2.14, p = 3.4E−06) were inhibited. Gene set enrichment analysis (GSEA) further indicated upregulation of cholesterol homeostasis and mTORC1 signaling. Our findings suggest that carotenoid-enriched LSBE modulates key pathways related to cellular homeostasis, antioxidant defense, and apoptosis in TNBC. While limited to transcriptional profiling, this exploratory study provides a foundation for future functional validation of LSBE as a complementary TNBC therapeutic approach.

17. Ovidiu Adrian Bitere, Corina-Elena Minciuna, Catalin Andras, Florina Almarii, Iulia Andrei-Bitere, Teodora Manuc, Aurel Tonea, Simona Olimpia Dima, Adina Croitoru, Vlad Herlea, Catalin Vasilescu
Artificial Intelligence in Colon Cancer: Advances, Challenges, and Future Perspectives. - Chirurgia (Bucur). 2026 Feb;121(1):13-26. doi: 10.21614/chirurgia.3240. PMID: 41789607

Abstract: Colorectal cancer (CRC) remains a significant global health challenge, with rising incidence in younger populations and high mortality. Artificial intelligence (AI) is transforming CRC care, enhancing accuracy and efficiency across diagnostic, therapeutic, and follow-up stages. In endoscopy, computer-aided detection (CADe) systems increase adenoma detection rates by 25â?"50%, while computer-aided diagnosis (CADx) supports real-time lesion characterization. In pathology, AI applied to whole-slide imaging enables automated triage, in silico microsatellite instability prediction, and prognostic risk stratification, often outperforming TNM staging. Radiology benefits from AI-driven lesion detection, staging, and radiomic â??virtual biopsyâ? for molecular profiling (e.g., KRAS, MSI). AI-based treatment planning integrates histopathology, imaging, and multi-omics to refine chemotherapy indications, predict neoadjuvant response, and identify novel therapeutic targets. In surgery, AI-enhanced robotic platforms enable real-time anatomical recognition, perfusion assessment, and complication risk prediction, improving intraoperative safety. Prognostic modeling using multimodal datasets offers superior survival and recurrence predictions, while AI-driven quality-of-life forecasting and patient-reported outcome monitoring facilitate personalized survivorship care. Challenges to widespread adoption include data heterogeneity, external validation gaps, interpretability, and regulatory compliance. Advances in multimodal AI and federated learning may overcome these barriers. With rigorous evaluation, AI is poised to become a cornerstone of precision oncology in CRC, improving outcomes and optimizing care delivery.

18. Leontina Banica 1 2, Robert Hohan 2, Ionelia Nicolae 2, Raluca Patrascu 1 2, Corina Casangiu 2 3, Simona Paraschiv 1 2, Voichita Elena Lazureanu 4, Valerica Bica Profir 5, Dimitrios Paraskevis 6, Dan Otelea 2
Evaluating HIV-1 Transmitted Drug Resistance and Clustering in Newly Diagnosed Patients in Romania (2019–2022) - Viruses. 2026 Jan 15;18(1):118. doi: 10.3390/v18010118

Abstract: The HIV epidemic in Romania started in the late eighties with a large cohort of children nosocomially infected with subtype F1 strains, in parallel with sexual transmission. The purpose of the present study was to investigate the transmitted drug resistance (TDR), subtype distribution, and transmission clusters among persons diagnosed with HIV between 2019 and 2022 in Romania. The prototype of a person recently diagnosed with HIV in Romania is male, 20–50 years old, a late presenter, infected with F1, B, or A subtype. The rate of TDR varied over time, from 5% in 2019 to 15% in 2022. TDR affected mainly the first generation of NNRTIs and the PI class. The rate of late presentation was almost 60%, with 35% of persons qualifying as very late presenters. Subtype F1 is still preponderant in Romania, whereas other subtypes (B, A) and recombinants account for a quarter of HIV-1 new cases. Several transmission networks were identified in the study population, two of them associated with TDR in subtypes F1 and A1. The largest cluster consisted of 26 sequences, originating from Western Romania and introduced around 2007. Molecular clock analysis indicated different origin time points for different clusters, with the most recent in subtypes A1 and B, and the oldest in subtype F1. In conclusion, the HIV-1 epidemic in Romania is currently driven by sexual transmission, with MSM contribution continuously rising in recent years; there are also increases in TDR and the circulation of HIV-1 strains other than F1 (subtype B, A, recombinants).

19. Ana Maria Chirilas, Alexandru Cărămizaru, Anca-Lelia Riza, Andreea Mitut-Veliscu, Andrei Costache, Rebecca-Cristiana Șerban, Aritina Morosanu, Carmen Niculescu, Alexandru-Cătălin Pâslaru, Florin Burada, Ioana Streata
Challenges in Diagnosis and Management of Coffin–Lowry Syndrome—Single-Center Experience - Diagnostics 2026, 16(7), 990; https://doi.org/10.3390/diagnostics16070990

Abstract: Background/Objectives: Coffin–Lowry syndrome (CLS) is a rare X-linked disease caused by pathogenic variants in the RPS6KA3 gene. It is generally characterized by syndromic intellectual disability and distinctive facial features, skeletal abnormalities, stimulus-induced drop attacks in males, and variable manifestations in females. Methods: We report clinical and genetic findings in a series of 10 cases, eight males and two females, evaluated at the Regional Centre of Medical Genetics Dolj—Emergency Clinical County Hospital Craiova. Results: Genetic testing identified 10 de novo variants in the RPS6KA3 gene consisting of six missense mutations, one nonsense variant, one frameshift, and two variants in non-coding or intronic regions. Case management requires multidisciplinary coordination and is limited to resources mostly available in reference centers. Conclusions: CLS highlights the importance of molecular diagnosis in rare genetic disorders, particularly when clinical features are subtle or atypical. These findings have practical implications for clinical management, suggesting the need for comprehensive genetic screening and individualized care approaches.

20. Petre Mihai Bogdan, Tăbîrcă Marius Sabin
Parallel String Matching on GPU: An Evaluation of KMP, Boyer-Moore, and BWT with CUDA - DOI: 10.1109/ICCP68926.2025.11427148

Abstract: String processing is a fundamental component of numerous applications in computer science, with particularly critical roles in areas such as bioinformatics, text mining, and data compression. In bioinformatics, efficient string matching underpins essential tasks like genome alignment, motif searching, and sequence assembly. However, traditional CPU-based implementations of string algorithms often struggle with the scale and complexity of modern data sets. This review explores the acceleration of classical string algorithms using NVIDIA’s CUDA platform for GPU computing. We examine and compare the performance and parallelization strategies of Knuth-MorrisPratt, Boyer-Moore and Burrows-Wheeler Transform when implemented on GPUs. The review analyzes how each algorithm’s structure affects its adaptability to CUDA’s parallel architecture, and evaluates their speedup, scalability, and memory efficiency across varying input sizes.

21. Mihai Emanuel Himcinschi, Mihaela Uta, Andreea Jercan, Daniel Murariu, Delia Codruta Popa, Valentina Uscatescu, Andrei Anghel, Daniel Coriu, Sorina Nicoleta Badelita
Hypercoagulability in Light Chain Amyloidosis and the Importance of Predictive Value of TEG and TGT for Thrombosis Recurrence in Inflammatory States - Diagnostics 2026, 16(7), 987; https://doi.org/10.3390/diagnostics16070987

Abstract: Background: Thrombosis in light chain amyloidosis (LCA) occurs in the context of multiple organ dysfunction and inflammation. Conventional coagulation tests (screening) may not sufficiently capture the procoagulant substrate in the inflammatory/therapeutic dynamics. Methods: A total of 61 consecutive patients with LCA were prospectively included in the study. Clinical data, including organ involvement, time of diagnosis, treatment phase, DOAC exposure and thrombosis history were systematically recorded and subjected to screening. Specialized hemostasis tests such as APTT/PT, fibrinogen, D-dimer, TEG and TGT were performed and conventional times were analyzed in the subgroup without DOAC. Results: The prevalence of documented thrombosis was 32.8%, and thrombosis status was associated with TEG positivity and more strongly with TGT positivity. Hypercoagulability was identified in 50.8% by TEG and 41.0% by TGT, regardless of whether APTT/PT were within the reference values. APTT/PT did not predict thrombosis recurrence (p > 0.05), which was predicted by TEG (p = 0.0027) and TGT (p = 0.0006). An inflammation/fibrin turnover panel (CRP, fibrinogen, D-dimer) predicted TEG positivity (p < 0.0001), but not TGT, and was correlated with assessment at diagnosis, daratumumab-based therapy, and cardiac involvement. Conclusions: Global tests (TEG/TGT) promptly correlate with thrombosis recurrence in our cohort and provide crucial information in addition to clotting times for thrombotic phenotyping. Inflammation can influence TEG, so the decision to recommend the tests and the timing of their performance should be adapted to the clinical, biological, and therapeutic context.

22. Ramona M. Tecucianu, Sorin Tunaru, Stefana M. Petrescu
G Protein-Coupled Receptors in Pancreatic β-Cells: From Trafficking and Localization to Insulin Secretion and Diabetes - Diabetology 2026, 7(4), 68; https://doi.org/10.3390/diabetology7040068

Abstract: G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and are critical regulators of β-cell physiology. Nearly 300 GPCRs are expressed in human islets, where they integrate metabolic, hormonal, neuronal, and inflammatory cues to control insulin secretion, proliferation, and survival. Altered GPCR signaling contributes to β-cell dysfunction and the pathogenesis of both type 1 and type 2 diabetes. This review provides an overview of GPCR functions in β-cell biology, highlighting receptors that stimulate or inhibit glucose-stimulated insulin secretion, as well as those influencing β-cell fate. We also examine GPCR biosynthesis, trafficking, and subcellular localization—processes that shape receptor availability and signaling specificity. Aberrant folding, retention, or misrouting of GPCRs can disrupt β-cell function and contribute to metabolic disease. Thus, beyond receptor pharmacology, understanding the molecular mechanisms governing GPCR biogenesis and spatial distribution is essential for designing targeted strategies to preserve β-cell function and improve glucose homeostasis.

23. Robert Onulov, Marius Georgescu, Corina Flangea, Adela Chirita-Emandi, Alina-Florina Serb
Intraoperative Mass Spectrometry in Oncology: Technologies, Clinical Applications, and Challenges - Molecules 2026, 31(8), 1287; https://doi.org/10.3390/molecules31081287

Abstract: Surgical precision is critical in oncology, where complete tumor resection while preserving healthy tissue directly influences patient outcomes. Traditional intraoperative diagnostic tools, such as frozen-section analysis, are limited by time constraints, tissue sampling, and interpretative variability. Intraoperative mass spectrometry (MS) has recently emerged as a transformative approach, enabling rapid, label-free molecular profiling of surgical specimens in real time. Several technologies—including Rapid Evaporative Ionization Mass Spectrometry (REIMS, “iKnife”), Desorption Electrospray Ionization (DESI-MS), Matrix-Assisted Laser Desorption/Ionization (MALDI-MS) Imaging, Picosecond InfraRed Laser mass spectrometry (PIRL-MS), and novel devices such as the MasSpec Pen—offer unique strategies for intraoperative tumor characterization. Applications have been demonstrated across multiple cancer types, including brain, breast, gastrointestinal, and urogenital malignancies, where MS can improve margin assessment, tumor classification, and surgical guidance. Beyond its clinical promise, intraoperative MS faces technical and translational challenges, including high infrastructure costs, a lack of standardization, and the need for robust multicenter validation. Integration with artificial intelligence, imaging modalities, and multi-omics approaches may further enhance its clinical utility. This review summarizes current technologies, clinical applications, limitations, and future perspectives of intraoperative MS in oncology, highlighting its potential to reshape surgical oncology practice.

24. Andrei Sorop, Alina-Veronica Ghionescu, Diana Larisa Ancuța, Maria-Gabriela Croitoru, Cristin Coman, Daniela Lixandru, Simona Olimpia Dima
Integrative transcriptomic analysis reveals miR-26a-5p downregulation and a potential predictive gene signature for the progression of metabolic liver disease - Front. Cell Dev. Biol., 20 April 2026; Sec. Cancer Cell Biology; Volume 14 - 2026 - https://doi.org/10.3389/fcell.2026.1805025

Abstract:

Background: Metabolic dysfunction–associated steatotic liver disease (MASLD) is an important inducer of hepatocellular carcinoma (HCC). MicroRNAs are key regulators of tumorigenesis. Among these, miR-26a-5p is known to be associated with liver pathogenesis, yet its role in linking MASLD progression to HCC development remains incompletely understood.

Methods: Hepatic miR-26a-5p expression was quantified in the C57BL/6 mice with a 3-month high-carbohydrate diet (HCD). Public transcriptomic datasets with MASLD and HCC samples were analyzed to identify predicted miR-26a-5p downstream candidates upregulated in the above-mentioned diseases. Associations with tumor features were examined, and protein expression of β-catenin, c-MYC and EpCAM were evaluated after miR-26a-5p modulation.

Results: Integrative bioinformatics identified miR-26a-5p as a candidate prognostic indicator for metabolic liver disease progression. In vivo, results confirmed that suppressed miR-26a-5p expression is a hallmark of diet-induced metabolic perturbation. Mechanistically, in vitro modulation of miR-26a-5p attenuated oncogenic signaling via the β-catenin/c-Myc/EpCAM axis, establishing its role as a tumor suppressor. Notably, in silico analysis of HCC tissues revealed that high miR-26a-5p levels correlate with enhanced antitumor immunity. Leveraging these insights, we constructed a transcriptional signature from miR-26a-5p downstream candidates and MASLD-HCC differentially expressed genes. This signature effectively stratifies MASLDpatients, discriminating molecular risk groups associated with progression to HCC.

Conclusion: Integrating transcriptomic, clinical and experimental data suggests the role of miR-26a-5p, along with the MASLD-HCC gene signature (EpCAM, DTNA, and KPNA2), may serve as an early molecular indicator and mechanistic modulator of hepatocarcinogenesis, warranting further functional investigation.

25. Vlad-Alexandru Ionescu, Gina Gheorghe, Claudiu Stefan Turculet, Teodor Florin Georgescu, Razvan Matei Bratu, Cristina Mambet, Valentin Enache, Mihaela Gheorghiu, Daniela Pasarica, Camelia Cristina Diaconu, Carmen Cristina Diaconu, Coralia Bleotu
Differential Plasma Expression of sTNF-R, TNF-α, PDGF-AA, IL-17A, and IL-1β Across the Colorectal Neoplasia Spectrum - Biomolecules 2026, 16(3), 426; https://doi.org/10.3390/biom16030426

Abstract: Colorectal cancer (CRC) remains one of the most important causes of cancer-related mortality worldwide, underscoring the need to better understand systemic inflammatory pathways across the colorectal neoplasia spectrum. In this exploratory case–control study, we characterized plasma levels of key inflammatory mediators in healthy individuals and patients with colorectal polyps or CRC. Healthy controls (n = 10), patients with colorectal polyps (CP, n = 16), early-onset CRC (EO-CRC, n = 11), and late-onset CRC (LO-CRC, n = 51) were prospectively enrolled. Plasma levels of sTNF-R, total TNF-α, PDGF-AA, IL-17A, and IL-1β were measured by ELISA. Group comparisons used Kruskal–Wallis tests with epsilon-squared effect sizes. PDGF-AA showed the strongest differences between controls and all neoplastic groups (ε² ≥ 0.15), and these comparisons remained significant after Benjamini–Hochberg false discovery rate correction. IL-17A levels were slightly higher in EO-CRC than in LO-CRC; however, this difference did not remain significant after adjustment for multiple testing. TNF-α and IL-1β showed no significant differences across groups. Overall, this study primarily provides descriptive and hypothesis-generating evidence of differential inflammatory patterns across colorectal neoplasia, with PDGF-AA emerging as the most robust signal in this exploratory dataset. These findings do not support immediate diagnostic application and require validation in larger, prospectively recruited cohorts.

26. Ioana-Stefania Bostan, Nicolae Gica, Mirela Mihaila, Marinela Bostan, Nicoleta Radu, Viviana Roman, Cristina-Elena Dinu-Pirvu, Valentina Uivarosi
Mitochondrial Long Non-Coding RNAs in Gynecological Cancers: Pathogenic Signaling Pathways and Therapeutic Opportunities - Curr. Issues Mol. Biol. 2026, 48(3), 261; https://doi.org/10.3390/cimb48030261

Abstract: Understanding the complex molecular mechanisms behind gynecological cancers is crucial, as these diseases pose significant challenges to women’s health and are frequently diagnosed at advanced stages. Various genetic, epigenetic, and metabolic alterations play a vital role in tumor development, metastasis, and therapy. Exploring mitochondrial dysfunction and the role of lncRNAs may provide essential insights into how tumor cells evade apoptosis, alter their metabolic pathways, and adapt to stress. In gynecological malignancies, nuclear lncRNAs contribute to tumor progression, treatment resistance, and metastasis through mechanisms that include chromatin remodeling, microRNA modulation, and regulation of mitochondrial dynamics. More recently, the emerging role of mt-lncRNAs, derived from the mitochondrial genome, has attracted attention for their involvement in retrograde signaling, mitochondrial respiration, and regulation of apoptosis. Dysregulation of mt-ncRNAs may contribute to tumor bioenergetic reprogramming, mitochondrial integrity, and nuclear gene expression. The objective of this review is to consolidate the current understanding of the regulatory mechanisms of mitochondrial lncRNAs in ovarian, cervical, and endometrial cancers, thus identifying new opportunities of research. A thorough elucidation of the role of mitochondrial lncRNAs in mitochondrial–nuclear communication may facilitate the development of new interventions in gynecological oncology, highlighting the potential of these molecules as diagnostic biomarkers and therapeutic targets.

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