Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported and underestimated. Both epidemiological and intervention studies show a bidirectional relationship between periodontitis and diabetes. The hypothesis of a potential causal link between the two diseases is corroborated by recent studies in experimental animals that identified mechanisms whereby periodontitis and diabetes can adversely affect each other. Herein, we will review clinical data on the existence of a two-way relationship between periodontitis and diabetes and discuss possible mechanistic interactions in both directions, focusing in particular on new data highlighting the importance of the host response. Moreover, we will address the hypothesis that trained immunity may represent the unifying mechanism explaining the intertwined association between diabetes and periodontitis. Achieving a better mechanistic insight on clustering of infectious, inflammatory, and metabolic diseases may provide new therapeutic options to reduce the risk of diabetes and diabetes-associated comorbidities.

Barotrauma in COVID-19 Patients

Clinical manifestations of COVID 19 is still unknown. We performed this study to determine the occurrence of pulmonary barotrauma as a complication of this disease. In this retrospective study, a total of 955 COVID 19 patients with respiratory insufficiency requiring oxygen support or invasive ventilation admitted to ICU of Sina Hospital from 20 March 2020 to 9 June 2021, were included and their chest imaging reviewed. Here, we report results of chest imaging of first 92 patients of this group. Barotrauma (pneumothorax, pneumomediastinum, pneumopericardium) occurred in 11 (11.9%) of 92 patients with coronavirus disease 2019 (COVID-19) infection requiring ICU admission for respiratory support and monitoring. It seems barotrauma is a common complication of COVID 19 disease. The role of increased respiratory efforts, patient or ventilation induced lung injury, viral and host response should be assessed. It needs to consider the occurrence of barotrauma in Patients with COVID-19, before expansion of dead space for treatment and limiting the ventilation effects.

The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis

Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection. Glycolysis plays a role in maintaining the immune function of macrophages, which is crucial for severely septic patients. However, how the pathways that link glycolysis and macrophages are regulated is still largely unknown. Here, we provide evidence to support the function of KLF14, a novel Krüppel-like transcription factor, in the regulation of glycolysis and the immune function of macrophages during sepsis. KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis. Mechanistically, KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2. In addition, we confirmed that the expression of KLF14 was upregulated in septic patients. Furthermore, pharmacological activation of KLF14 conferred protection against sepsis in mice. These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.

Residual Bioprosthetic Valve Immunogenicity: Forgotten, Not Lost

Despite early realization of the need to control inherent immunogenicity of bioprosthetic replacement heart valves and thereby mitigate the ensuing host response and its associated pathology, including dystrophic calcification, the problem remains unresolved to this day. Concerns over mechanical stiffness associated with prerequisite high cross-link density to effect abrogation of this response, together with the insinuated role of leaching glutaraldehyde monomer in subsequent dystrophic mineralization, have understandably introduced compromises. These have become so entrenched as a benchmark standard that residual immunogenicity of the extracellular matrix has seemingly been relegated to a very subordinate role. Instead, focus has shifted toward the removal of cellular compartment antigens renowned for their implication in the failure of vascularized organ xenotransplants. While decellularization certainly offers advantages, this review aims to refocus attention on the unresolved matter of the host response to the extracellular matrix. Furthermore, by implicating remnant immune and inflammatory processes to bioprosthetic valve pathology, including pannus overgrowth and mineralization, the validity of a preeminent focus on decellularization, in the context of inefficient antigen and possible residual microbial remnant removal, is questioned.