The novel corona virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and the disease it causes, COVID-19 (Coronavirus Disease-2019) have had multi-faceted effects on a number of lives on a global scale both directly and indirectly. A growing body of evidence suggest that COVID-19 patients experience several oral health problems such as dry mouth, mucosal blistering, mouth rash, lip necrosis, and loss of taste and smell. Periodontal disease (PD), a severe inflammatory gum disease, may worsen the symptoms associated with COVID-19. Routine dental and periodontal treatment may help decrease the symptoms of COVID-19. PD is more prevalent among patients experiencing metabolic diseases such as obesity, diabetes mellitus and cardiovascular risk. Studies have shown that these patients are highly susceptible for SARS-CoV-2 infection. Pro-inflammatory cytokines and oxidative stress known to contribute to the development of PD and other metabolic diseases are highly elevated among COVID-19 patients. Periodontal health may help to determine the severity of COVID-19 infection. Accumulating evidence shows that African-Americans (AAs) and vulnerable populations are disproportionately susceptible to PD, metabolic diseases and COVID-19 compared to other ethnicities in the United States. Dentistry and dental healthcare professionals are particularly susceptible to this virus due to the transferability via the oral cavity and the use of aerosol creating instruments that are ubiquitous in this field. In this review, we attempt to provide a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the various effects it has had on the dental profession and patients visits to dental clinics. Finally, this review is a valuable resource for the management of oral hygiene and reduction of the severity of infection.

Background/Objectives: Periodontal disease (PD) is a chronic inflammatory condition caused by dysbiosis of the oral microbiome. PD is linked to systemic inflammation and endothelial dysfunction, which associate it with cardiovascular disease (CVD). This systematic review explores the molecular and microbial mechanisms through which periodontal pathogens, including “Red Complex” bacteria (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and Fusobacterium nucleatum, influence cardiovascular health via inflammatory pathways, immune modulation, and microbial dissemination. Methods: A systematic review was conducted following PRISMA guidelines. A literature search was conducted in the PubMed and ScienceDirect databases using relevant keywords, with strict inclusion and exclusion criteria, from the first week of September 2024 to the first week of October 2024. Studies addressing the relationship between PD and CVD were assessed for methodological rigor, relevance, and data availability. The outcomes were synthesized using a descriptive narrative approach. Out of 591 records screened, 421 full-text articles were sought for retrieval. The final review included 58 articles providing supplementary aggregated data after eligibility assessment. Results: The pathogenesis of PD involves the activation of immune cells and the release of pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α, and PGE2) and chemokines (including IL-8 and MCP-1) along with oxidative stress driven by reactive oxygen species (ROS). Periodontal pathogens trigger endothelial oxidative stress and systemic inflammation via Toll-like receptors (TLRs), NF-κB signaling, and nitric oxide (NO) dysregulation, contributing to endothelial dysfunction and atherogenesis. Biomarkers, such as C-reactive protein, interleukins, and matrix metalloproteinases (MMPs), further highlight the systemic inflammatory response. Conclusions: This review underscores the significant role of periodontal pathogens and inflammatory mediators in systemic health, particularly in the progression of CVD. Although existing evidence illustrates these associations, the underlying molecular mechanisms remain inadequately understood, indicating a need for further research to advance precision medicine and therapeutic strategies.

Porphyromonas gingivalis (Pg), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against P. gingivalis (W83) and Pg-derived lipopolysaccharide (Pg-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells. IEC-6 (ATCC, CRL-1592) cells were pretreated with or without CNM (100 µM), in the presence or absence of P. gingivalis (strain W83, 10⁹ MOI) or Pg-LPS (1, 10, and 100 µg/mL), respectively, between 0–72 h time points by adopting a co-culture method. Intestinal barrier function, cytokine secretion, and intestinal oxidative stress protein markers were analyzed. P. gingivalis or Pg-LPS significantly (p < 0.05) increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels expressing oxidative stress damage. Pg-LPS, as well as Pg alone, induces inflammatory cytokines via TLR-4 signaling. Furthermore, infection reduced Nrf2 and NAD(P)H quinone dehydrogenase 1 (NQO1). Interestingly, inducible nitric oxide synthase (iNOS) protein expression significantly (p < 0.05) increased with Pg-LPS or Pg infection, with elevated levels of nitric oxide (NO). CNM treatment suppressed both Pg- and Pg-LPS-induced intestinal oxidative stress damage by reducing ROS, MDA, and NO production. Furthermore, CNM treatment significantly upregulated the expression of tight junction proteins via increasing the phosphorylation levels of PI3K/Akt/Nrf2 suppressing inflammatory cytokines. CNM protected against Pg infection-induced intestinal epithelial barrier dysfunction by activating the PI3K/Akt-mediated Nrf2 signaling pathway in IEC-6 cells.

Gastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to investigate whether supplementation of 17β-estradiol (E₂) or progesterone (P₄) restores impaired nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive transcription factor) and nitric oxide (NO)-mediated gastric motility in ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). Groups of OVX+HFD mice were administered daily subcutaneous doses of either E₂ or P₄ for 12 weeks. The effects of E₂ and P₄ on body weight, metabolic homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite levels, neuronal nitric oxide synthase (nNOSα), and its cofactor expression levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and insulinemia while accelerating GE (p < 0.05) in OVX mice. Exogenous E₂, but not P₄, attenuated rapid gastric emptying and restored gastric nitrergic relaxation, total nitrite levels, nNOSα, and cofactor expression via normalizing Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E₂ is beneficial in normalizing metabolic homeostasis and gastric emptying in obese, diabetic OVX mice consuming a fat-rich diet.

Gastroparesis (Gp) is a severe complication of diabetes mellitus (DM) observed predominantly in women. It is characterized by abnormal gastric emptying (GE) without mechanical obstruction in the stomach. Nitric oxide (NO) is an inhibitory neurotransmitter produced by neuronal nitric oxide synthase (nNOS). It plays a critical role in gastrointestinal (GI) motility and stomach emptying. Here, we wanted to demonstrate the protective effects of supplemental 17β-estradiol (E₂) on NO-mediated gastric function. We showed E₂ supplementation to alleviate oxidative and inflammatory stress in streptozotocin (STZ)-induced diabetic female mice. Our findings suggest that daily administration of E₂ at therapeutic doses is beneficial for metabolic homeostasis. This restoration occurs via regulating and modulating the expression/function of glycogen synthase kinase-3β (GSK-3β), nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), Phase II enzymes, MAPK- and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB)-mediated inflammatory cytokines (IL-1β, IL-6, TNFα, IGF-1), and gastric apoptotic regulators. We also showed E₂ supplementation to elevate GCH-1 protein levels in female diabetic mice. Since GCH-1 facilitates the production of tetrahydrobiopterin (BH₄, cofactor for nNOS), an increase in GCH-1 protein levels in diabetic mice may improve their GE and nitrergic function. Our findings provide new insights into the impact of estrogen on gastric oxidative stress and intracellular inflammatory cascades in the context of Gp.

INPLASY202510055 Unveiling the Molecular Crosstalk Between Periodontal and Cardiovascular Diseases: A Systematic Review Keywords: Periodontal disease, Oral microbiota, Red complex bacteria, Cardiov…