Juan Antonio Arreguín-Cano

Background/Objectives: Second-degree burns require strategies that address microbial contamination, oxidative stress, exudate, and tissue repair. This study aimed to develop and evaluate a marine-derived chitosan hydrogel incorporating ethanolic extract of propolis (EEP) from Chihuahua, Mexico, for second-degree burn management. Methods: EEP was characterized using parameters established in NOM-003-SAG/GAN-2017 and complementary biological assays. Chitosan hydrogels containing 1%, 3%, and 5% (w/w) EEP were evaluated for physicochemical properties, swelling, mass loss, flavonoid release, antioxidant activity, antimicrobial performance, and cell viability. The 1% EEP hydrogel was further evaluated in a murine second-degree burn model. Results: Chihuahua propolis exhibited high phenolic (27.42 ± 2.53%) and flavonoid (9.23 ± 0.314%) contents. EEP incorporation modified the chitosan matrix, providing high swelling capacity, increased structural persistence, sustained flavonoid release for 72 h, and radical-scavenging activity for 96 h. Antimicrobial activity was concentration-dependent, with the 5% EEP hydrogel reducing recoverable Escherichia coli counts below the detection limit (2 CFU/mL). However, EEP-containing hydrogels reduced NIH-3T3 viability below the 70% ISO 10993-5 threshold under static extraction conditions. At 144 h, the 1% EEP hydrogel produced greater wound contraction than silver sulfadiazine (p = 0.021), although it did not differ significantly from the propolis-free chitosan hydrogel or untreated control. Qualitative histological assessment showed features consistent with early tissue repair, with cutaneous appendages observed in several sections from the 1% EEP group. Conclusions: Chihuahua propolis-loaded chitosan hydrogels showed promising physico-chemical, release, antioxidant, antimicrobial, and short-term in vivo findings. The in vitro reduction in metabolic activity observed under static extraction conditions warrants further evaluation using physiologically relevant exposure models, extended follow-up, and comprehensive safety assessment.

Periodontitis (P) and Type 2 Diabetes Mellitus (T2DM) are chronic inflammatory diseases that share pathophysiological pathways involving immune dysregulation and oxidative stress. Both conditions have been associated with increased susceptibility to viral infections, including SARS-CoV-2. In this regard, molecules associated with viral infection include angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). This study aimed to evaluate the clinical periodontal status, oral microbiota composition, and the expression of ACE2 and TMPRSS2 in the oral epithelium and gingival tissue of patients with and without T2DM and P. Methods: This cross-sectional study enrolled 120 participants allocated into four groups based on periodontal and glycemic status: periodontally healthy non-diabetic individuals (PH non-T2DM), periodontitis without diabetes (P non-T2DM), periodontally healthy individuals with type 2 diabetes mellitus (PH T2DM), and periodontitis with T2DM (P T2DM), with 30 participants per group. Full-mouth clinical periodontal parameters were recorded by a calibrated examiner. Oral microbiota was assessed from unstimulated whole saliva, labial swab samples, and subgingival biofilm by selective culture and checkerboard DNA-DNA hybridization. Gingival exfoliative cytology and full-thickness gingival biopsies were obtained for immunohistochemical evaluation of ACE2 and TMPRSS2 expression. Cytomorphometric analysis and polymorphonuclear cell counts were performed on epithelial smears. Additionally, primary human gingival fibroblasts (HGFs) isolated from each group were stimulated with bacterial ligands (LPS, LTA, and PGN) to assess ACE2 and TMPRSS2 modulation by Western blot. Intergroup comparisons were performed using one-way ANOVA with Bonferroni post hoc correction and the Mann–Whitney U test, with statistical significance set at p < 0.05. Results: Diabetic patients exhibited higher plaque accumulation, clinical attachment loss, and bleeding on probing compared with non-diabetic individuals (p < 0.05). The diabetic groups showed significantly higher levels of Actinomyces, Fusobacterium, and Streptococcus spp., with decreased Staphylococcus counts. ACE2 and TMPRSS2 expression were markedly elevated in gingival epithelial cells of P T2DM patients, predominantly in basal and suprabasal layers. The nuclear-to-cytoplasmic ratio and polymorphonuclear cell counts were also increased in diabetic subjects. Conclusions: T2DM and P synergistically upregulate ACE2 and TMPRSS2 expression and alter the oral microbiota.

Persistent endodontic infections are frequently associated with Enterococcus faecalis, a microorganism capable of penetrating dentinal tubules and surviving conventional disinfection procedures. This in vitro study evaluated the antimicrobial activity of Chihuahuan propolis against E. faecalis using planktonic and intratubular infection models. Propolis extract was tested at concentrations of 15, 35, and 70 mg/mL and compared with triple antibiotic paste (TAP) as a clinically relevant intracanal medicament. Antimicrobial efficacy was assessed by disk diffusion, minimum inhibitory concentration (MIC), colony-forming unit (CFU) reduction in infected dentinal tubules, and scanning electron microscopy (SEM). Chihuahuan propolis exhibited concentration-dependent antimicrobial activity, with a MIC of 17.5 mg/mL. In the intratubular model, propolis at 70 mg/mL achieved a CFU reduction comparable to TAP after seven days of application. SEM analysis confirmed a marked reduction of bacterial colonization within dentinal tubules. Within the limitations of this in vitro, monoespecies model, Chihuahuan propolis demonstrated antimicrobial efficacy against E. faecalis comparable to TAP, supporting its further investigation as a potential non-antibiotic intracanal medicament.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder increasingly recognized as a systemic inflammatory condition with significant neurological effects. Growing evidence shows that chronic low-grade inflammation (CLGI), insulin resistance, and metabolic imbalance contribute to cognitive decline and the development of neurodegenerative diseases like Alzheimer’s and Parkinson’s. Toll-like receptor 2 (TLR2), a critical pattern-recognition receptor of the innate immune system, has emerged as an essential molecular link between metabolic dysfunction and neuroinflammation and neuronal damage. This review summarizes current experimental, clinical, and translational evidence on the role of TLR2 in T2DM-related inflammation, mitochondrial dysfunction, lipid imbalance, insulin resistance, and blood–brain barrier (BBB) issues. We explore how ongoing TLR2 activation by internal danger signals and metabolic stressors maintains systemic inflammation and fuels neuroimmune responses via microglial activation and cytokine release, thereby accelerating neurodegenerative processes. Additionally, we discuss new therapeutic strategies targeting TLR2 signaling, including drugs, dietary supplements, and the repurposing of antidiabetic medications with neuroprotective effects. By combining immunometabolic and neurodegenerative pathways, this review highlights TLR2 as a promising target for preventing or reducing diabetes-related cognitive decline neurodegeneration.

Background: Growing evidence indicates that oral microbiome dysbiosis contributes to systemic inflammation, immune activation, and neural dysfunction. These processes may influence the onset and progression of major neuropsychiatric and neurodegenerative disorders. This review integrates clinical, epidemiological, and mechanistic findings linking periodontal pathogens and oral microbial imbalance to Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, and anxiety. Methods: A narrative review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify recent studies examining alterations in the oral microbiota, microbial translocation, systemic inflammatory responses, blood–brain barrier disruption, cytokine signaling, and neural pathways implicated in brain disorders. Results: Evidence from human and experimental models demonstrates that oral pathogens, particularly Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, can disseminate systemically, alter immune tone, and affect neural tissues. Their virulence factors promote microglial activation, cytokine release (IL-1β, IL-6, TNF-α), amyloid-β aggregation, and α-synuclein misfolding. Epidemiological studies show associations between oral dysbiosis and cognitive impairment, motor symptoms in PD, and alterations in mood-related taxa linked to stress hormone profiles. Immunometabolic pathways, HPA-axis activation, and the oral–gut–brain axis further integrate these findings into a shared neuroinflammatory framework. Conclusions: Oral dysbiosis emerges as a modifiable contributor to neuroinflammation and brain health. Periodontal therapy, probiotics, prebiotics, synbiotics, and targeted inhibitors of bacterial virulence factors represent promising strategies to reduce systemic and neural inflammation. Longitudinal human studies and standardized microbiome methodologies are still needed to clarify causality and evaluate whether restoring oral microbial balance can modify the course of neuropsychiatric and neurodegenerative disorders.