Liliana Mititelu-Tartau

Background/Objectives: Periodontitis is sustained by dysbiotic biofilms and dysregulated host responses, providing pharmacological targets for antimicrobial, host-modulating, phytochemical, regenerative, and locally delivered interventions. This scoping review mapped bioactive heterocyclic compounds investigated in periodontitis according to the structural family, pharmacological target, periodontal compartment, therapeutic maturity, selected periodontal–systemic interfaces, and a secondary geriatric cerebrovascular context. Methods: PubMed, Scopus, and the Web of Science Core Collection were searched for the principal review on 30 July 2026. Companion publications were linked at the study level, and design-specific appraisal was applied when sufficient methodological information was available. A separate cerebrovascular extension was searched on 6 August 2026 and analyzed independently of the principal evidence denominator. Results: The principal evidence map comprised 715 independent studies represented by 804 canonical eligible reports. Nitroimidazole-containing regimens formed the largest structural family (283 studies; 39.6%), followed by melatonin and indole-related agents (83; 11.6%), macrolides (77; 10.8%), berberine and isoquinoline-related compounds (29; 4.1%), and quinolones or fluoroquinolones (28; 3.9%). Human clinical evidence was concentrated mainly in established antimicrobial regimens, whereas many host-modulating, phytochemical, regenerative, signaling, and delivery-based approaches remained predominantly translational or preclinical. The detailed clinical subset comprised 48 human studies, including six core comparative studies; heterogeneity in population, regimen, treatment background, follow-up, outcome definition, and analysis unit precluded a clinically meaningful pooled estimate. Prespecified systemic interfaces included diabetes (35 studies), cardiovascular disease (13), and rheumatoid arthritis (2). The separate cerebrovascular component comprised 30 studies addressing the oral health burden, microbial and inflammatory associations, oral care interventions, and treatment safety considerations in older adults with ischemic stroke. Conclusions: The evidence supports compound- and formulation-specific interpretation rather than class-wide therapeutic recommendations. Clinical translation should integrate structural and mechanistic plausibility with periodontal target-site exposure, pharmacokinetic–pharmacodynamic evidence, clinically meaningful benefit, safety, and antimicrobial stewardship. The cerebrovascular evidence supports oral care integration and safety surveillance but does not establish causal periodontal effects on stroke, reperfusion outcomes, or thrombolysis eligibility.

Oncology and cardiology use paclitaxel, a powerful cell-division inhibitor. Paclitaxel-eluting coated metal stents in oncology prevent tumor growth by modulating proliferation, apoptosis, and angiogenesis. Paclitaxel-eluting stents reduce in-stent restenosis and maintain arterial patency in cardiology. Paclitaxel encapsulated in liposomes improves targeted administration, pharmacokinetics, and therapeutic efficacy. Liposome-loaded paclitaxel has a stronger anti-tumor effect than standard formulations. Paclitaxel plus sirolimus in a stent may synergistically prevent restenosis and inhibit tumors. Liposomal formulations with supplemental medications offer promising prospects for improving therapeutic accuracy and efficacy. Liposomal paclitaxel enhances targeted drug delivery, which may improve cancer treatment and cardiovascular treatments such as drug-eluting stents and drug-coated balloons in interventional radiology. Advanced delivery technologies have changed paclitaxel drug delivery methods for therapeutic use by overcoming its low solubility and systemic toxicity. Nanocrystals and liposomes enable high drug loading and precise targeted delivery, and, by eliminating toxic solvents such as Cremophor EL, they improve the safety and efficacy of cancer therapy.

Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, inflammation, and progressive hepatic and pancreatic dysfunction. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors exert metabolic and organ-protective effects, their ability to preserve pancreatic architecture and attenuate diabetes-associated hepatic injury, particularly combined with nutritional interventions, remains insufficiently explored. This study investigated the protective effects of dapagliflozin (DAPA) and empagliflozin (EMPA), alone or combined with zinc (Zn), on hepatic and pancreatic alterations in experimental diabetes. Methods: Diabetes was induced in male Sprague–Dawley rats using streptozotocin (STZ) and high fat diet (HFD). Diabetic animals received DAPA, EMPA, Zn, or SGLT2 inhibitor–Zn combinations for four weeks. Hepatic biochemical parameters, lipid profile, histopathology, pancreatic morphometry, and insulin immunoreactivity were evaluated. Diabetes induced hepatic and pancreatic alterations, including elevated liver injury markers, hepatocellular degeneration, reduced islet number and β-cell density, and diminished insulin immunoreactivity. DAPA and EMPA attenuated these changes, with greater improvements following Zn combination therapy. EMPA + Zn produced the most favorable response, improving hepatic architecture, reducing VCAM-1, ICAM-1, and NF-κB expression, preserving islet morphology, increasing β-cell density, and enhancing insulin immunoreactivity. SGLT2 inhibitors attenuated diabetes-associated hepatic and pancreatic alterations in this experimental model, while Zn supplementation was associated with additional tissue-preserving effects, particularly when combined with EMPA. These findings support further investigation of combined SGLT2 inhibition and Zn supplementation as an experimental approach to diabetes-associated organ injury; however, their clinical relevance remains to be established.

Monoclonal antibody-based therapies are widely used in chronic immune-mediated diseases, but their periodontal effects, dentoalveolar safety signals, and exposure characteristics remain incompletely characterized. This scoping review mapped periodontal clinical outcomes, biomarkers, microbiological and imaging findings, dentoalveolar safety, administration, treatment exposure, and pharmaceutical-context reporting. PubMed, Scopus, and Web of Science were searched in July 2026 without publication-year or language restrictions. Twenty-one reports representing 20 studies or cohort families were included. Evidence mainly concerned rheumatoid arthritis and therapies targeting tumor necrosis factor, interleukin-6 receptor, and cluster of differentiation 20. Evidence for interleukin-17A inhibition was insufficient and derived from one confounded five-patient case series. Tocilizumab showed the most consistent reductions in gingival inflammation and bleeding on probing, while structural changes were smaller and inconsistent. Tumor necrosis factor-directed findings were heterogeneous. Small rituximab studies showed favorable clinical or biomarker signals, whereas pharmacovigilance identified infectious and destructive dentoalveolar signals. Exposure reporting was incomplete, and no included periodontal study evaluated formulation stability, storage, cold-chain integrity, or handling deviations. This review integrates treatment-effect evidence, safety signals, and exposure variables across antibody targets and identifies a pharmaceutical–periodontal reporting gap requiring prospective investigation.

Background/Objectives: Colistin is a last-resort agent against multidrug-resistant Gram-negative infections and is administered predominantly to complex, comorbid inpatients in whom mortality is high. We aimed to identify independent baseline predictors of in-hospital mortality in colistin-treated patients and to characterize temporal changes in mortality over 15 years. Methods: We conducted a retrospective cohort study of 1225 consecutive patients receiving systemic colistin between November 2009 and November 2024 at Parhon Hospital, a tertiary urology–nephrology center in Iași, Romania; independent predictors of death were identified using multivariable logistic regression restricted to variables fixed at the time of colistin initiation, reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Patients were predominantly male (60.2%), with a mean age of 65.1 ± 14.4 years; 85.6% were admitted to urology or nephrology. In-hospital mortality was 27.6%. Mortality was independently associated with acute kidney injury (aOR 3.72, 95% CI 2.76–5.01), sepsis (aOR 2.79, 95% CI 2.11–3.70), emergency admission (aOR 1.91, 95% CI 1.40–2.61), Charlson comorbidity index (aOR 1.13 per point, 95% CI 1.05–1.22), and older age (aOR 1.03 per year, 95% CI 1.02–1.04); sex was not associated. Crude mortality increased across the study period (odds ratio 1.16 per year, 95% CI 1.13–1.20) and remained elevated after adjustment for case-mix (adjusted odds ratio 1.13 per year, 95% CI 1.09–1.17). Conclusions: Acute kidney injury, sepsis, emergency admission, comorbidity burden, and age were independently associated with in-hospital death. Mortality rose progressively over 15 years, only partly explained by an increasingly severe case-mix, supporting early risk stratification of colistin recipients.

Background: Paclitaxel is a cornerstone chemotherapeutic agent widely used in breast cancer treatment, primarily through the stabilization of microtubule dynamics. Beyond its canonical tubulin-targeting activity, increasing evidence suggests that paclitaxel may engage additional molecular targets, contributing to its complex pharmacological profile. In this study, an integrated computational workflow was applied to evaluate the structural compatibility between paclitaxel and the neurokinin-2 receptor (NK2R), a G protein-coupled receptor involved in tumor-associated inflammatory and proliferative signaling pathways. Physicochemical profiling and target prediction were performed using SwissADME and SwissTargetPrediction, followed by molecular docking and molecular dynamics simulations using AutoDock Vina and GROMACS 2024.1. Paclitaxel exhibited physicochemical properties consistent with transient interactions in hydrophobic transmembrane environments. Docking analysis identified a plausible binding mode within the NK2R transmembrane cavity, primarily stabilized by hydrophobic contacts. Molecular dynamics simulations over 100 ns revealed stable ligand occupancy and overall complex stability, while MM-PBSA calculations indicated a favorable transient association. The predicted interaction is consistent with secondary or non-canonical receptor engagement. While NK2R is not established as a pharmacological target of paclitaxel, the results support the structural feasibility of a previously uncharacterized receptor interaction and provide a reproducible computational framework for exploring GPCR-associated effects of cytotoxic agents.

Background and Objectives: Topical diclofenac is recommended over oral non-steroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis, particularly in older adults and those with comorbidities, on the assumption that low systemic absorption limits renal effects. Whether this presumed safety extends to patients already at increased risk of kidney injury has not been systematically evaluated. This review assessed the evidence on renal outcomes of topical diclofenac in adults. Materials and Methods: We conducted a systematic review (PROSPERO CRD420261393454) of studies reporting renal outcomes after topical diclofenac exposure. PubMed, Embase, Web of Science, and Scopus were searched from inception to 19 April 2026. Studies were stratified a priori into increased-renal-risk and general populations and synthesised separately, without pooling. Risk of bias was assessed with RoB 2, ROBINS-I, and JBI tools, certainty with GRADE, and synthesis followed the SWiM framework. Results: Eighteen studies, contributing data from more than 500,000 participants, were included; 14 underwent primary risk-of-bias appraisal (three at low, three at serious or high risk). In general populations, topical diclofenac produced little to no change in serum creatinine or creatinine clearance and smaller renal effects than oral diclofenac, providing high-certainty evidence of a favourable profile. In increased-renal-risk populations, one adjusted cohort reported higher acute kidney injury (AKI) risk among topical NSAID users, although exposure was predominantly to non-diclofenac agents; within the same cohort, topical NSAIDs carried lower risk than systemic NSAIDs. No study evaluated early renal injury biomarkers; certainty was moderate owing to indirectness. Conclusions: Relative to oral diclofenac, topical diclofenac shows a favourable renal safety profile, with high-certainty evidence in general populations. In adults at increased renal risk, moderate-certainty evidence derived from predominantly non-diclofenac exposure over short observation windows cannot exclude a modest excess of any-stage AKI; renal risk therefore appears reduced rather than absent. Diclofenac-specific studies in chronic kidney disease using sensitive biomarkers and longer follow-up are needed.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of pharmacological treatment for osteoarthritis (OA) and are recommended by international guidelines for the management of symptomatic pain. Despite their well-established efficacy, substantial interindividual variability exists in treatment response, with some patients experiencing meaningful pain relief while others derive little clinical benefit despite appropriate drug selection and dosing. This variability reflects, at least in part, the biological heterogeneity of OA pain. Objective: To review the mechanisms underlying variability in NSAID responsiveness in OA and to propose a practical framework for personalized NSAID prescribing based on pain phenotype, individual safety profile, and treatment timing. Methods: A narrative review of the contemporary scientific literature was conducted using major biomedical databases to summarize the current evidence on phenotype-guided NSAID therapy in OA. Particular attention was given to the emerging concepts of nociceptive, nociplastic, and neuropathic-like pain phenotypes and their implications for personalized anti-inflammatory therapy. Results: Current evidence indicates that OA pain is a heterogeneous and dynamic condition in which inflammatory nociceptive, nociplastic, and neuropathic-like mechanisms coexist to varying degrees. NSAIDs primarily target inflammatory nociceptive pain by inhibiting cyclooxygenase (COX)-mediated prostaglandin synthesis and reducing peripheral sensitization. Consequently, patients with predominantly inflammatory nociceptive pain are the most likely to benefit from NSAID therapy, whereas those with predominant nociplastic or neuropathic-like pain mechanisms may require alternative or multimodal treatment strategies. Beyond pain phenotype, optimal NSAID selection should integrate cardiovascular, gastrointestinal, and renal risk assessment, recognizing the important pharmacological and safety differences among individual agents. Treatment timing is also clinically relevant, as anti-inflammatory therapy appears most effective when initiated during periods of active inflammatory nociceptive pain. Based on the available evidence, we propose a conceptual clinical decision framework integrating patient selection, NSAID choice, and treatment timing. Conclusions: Personalized NSAID prescribing should move beyond a diagnosis-based approach toward a mechanism-based strategy that integrates pain phenotyping, individualized safety assessment, and appropriate treatment timing. The proposed framework is built upon three complementary principles, identifying the right patient, selecting the right treatment, and initiating therapy at the right time. It provides a practical foundation for implementing precision medicine in the pharmacological management of OA.

Monoclonal antibody-based therapies are widely used in chronic immune-mediated diseases, yet periodontal effects, dentoalveolar safety signals and exposure characteristics remain incompletely characterized. This scoping review mapped periodontal outcomes, safety signals, administration, exposure and pharmaceutical-context reporting in adults. PubMed, Scopus and Web of Science were searched in July 2026 without publication-year or language restrictions. Sources were selected using Population, Concept and Context criteria, appraised with design-specific Joanna Briggs Institute tools and synthesized by therapeutic target. Of 1154 records, 21 reports representing 20 studies or cohort families were included. Evidence concentrated on rheumatoid arthritis and therapies targeting tumour necrosis factor, interleukin-6 receptor, cluster of differentiation 20, or interleukin-17A. Tocilizumab showed the most consistent reductions in gingival inflammation and bleeding on probing, whereas structural changes were smaller and inconsistent. Tumour necrosis factor-directed findings were heterogeneous; small rituximab studies showed favourable clinical or biomarker signals, while pharmacovigilance contained infectious and destructive dentoalveolar signals. Intravenous and subcutaneous administration were represented, but exposure reporting was incomplete. No included periodontal study evaluated formulation stability, storage, cold-chain integrity, or handling deviations. Risk-based periodontal surveillance may accompany therapy, but validated protocols cannot be defined. The identified gap concerns integrating pharmaceutical-context variables into periodontal research, not monoclonal-antibody stability research generally.

Background and Objectives: Diabetes mellitus is a major systemic modifier of oral infection, periodontal inflammation, and tissue healing. Persistent hyperglycemia may intensify oxidative stress, immune dysfunction, dysbiotic biofilm activity, and advanced glycation end-product/receptor signaling, thereby reducing the predictability of periapical and periodontal healing. In patients with endo-periodontal lesions, these mechanisms may interact with pulpal infection and periodontal breakdown, complicating diagnosis, prognosis, and therapeutic sequencing. This review summarizes current evidence on diabetes, glycated hemoglobin (HbA1c), and endo-periodontal outcomes and proposes an HbA1c-guided clinical framework for risk stratification and treatment planning. Materials and Methods: A structured narrative review with an expert-informed clinical framework was conducted using the literature published between January 2016 and December 2025. Eligible sources included consensus reports, clinical practice guidelines, systematic reviews, meta-analyses, umbrella reviews, randomized and non-randomized clinical studies, observational studies, and selected mechanistic studies or contemporary narrative reviews with direct relevance to the framework. Case reports, animal studies, and in vitro investigations without direct relevance to the clinical framework were excluded from the main synthesis. Results: Diabetes is associated with increased periodontal severity, impaired periodontal treatment response, a higher prevalence of radiolucent periapical lesions in root-filled teeth, delayed periapical healing, and increased non-retention of endodontically treated teeth. Periodontal therapy is safe in diabetic patients and may be associated with modest reductions in HbA1c, especially when baseline metabolic control is poor. Conclusions: HbA1c should complement, not replace, pulpal testing, periodontal charting, and radiographic assessment. The proposed framework prioritizes endodontic infection control when pulpal necrosis or active intracanal infection is present, adapts periodontal intervention to metabolic risk, and postpones elective surgical or regenerative procedures in poorly controlled diabetes until medical stabilization is achieved.