Pro-inflammatory Immune Response Research Articles

Human social genomics: Concepts, mechanisms, and implications for health.

The exciting field of human social genomics provides an evolutionarily informed, multilevel framework for understanding how positive and negative social-environmental experiences affect the genome to impact lifelong health, well-being, behavior, and longevity. In this review, we first summarize common patterns of socially influenced changes in the expression of pro-inflammatory and antiviral immune response genes (e.g., the Conserved Transcriptional Response to Adversity), and the multilevel psychological, neural, and cell signaling pathways by which social factors regulate human gene expression. Second, we examine how these effects are moderated by genetic polymorphisms and the specific types of social-environmental experiences that most strongly affect gene expression and health. Third, we identify positive psychosocial experiences and interventions that have been found to impact gene expression. Finally, we discuss promising opportunities for future research on this topic and how health care providers can use this information to improve patient health and well-being.

Molecular Targets in Campylobacter Infections

Human campylobacteriosis results from foodborne infections with Campylobacter bacteria such as Campylobacter jejuni and Campylobacter coli, and represents a leading cause of bacterial gastroenteritis worldwide. After consumption of contaminated poultry meat, constituting the major source of pathogenic transfer to humans, infected patients develop abdominal pain and diarrhea. Post-infectious disorders following acute enteritis may occur and affect the nervous system, the joints or the intestines. Immunocompromising comorbidities in infected patients favor bacteremia, leading to vascular inflammation and septicemia. Prevention of human infection is achieved by hygiene measures focusing on the reduction of pathogenic food contamination. Molecular targets for the treatment and prevention of campylobacteriosis include bacterial pathogenicity and virulence factors involved in motility, adhesion, invasion, oxygen detoxification, acid resistance and biofilm formation. This repertoire of intervention measures has recently been completed by drugs dampening the pro-inflammatory immune responses induced by the Campylobacter endotoxin lipo-oligosaccharide. Novel pharmaceutical strategies will combine anti-pathogenic and anti-inflammatory effects to reduce the risk of both anti-microbial resistance and post-infectious sequelae of acute enteritis. Novel strategies and actual trends in the combat of Campylobacter infections are presented in this review, alongside molecular targets applied for prevention and treatment strategies.

Major Depressive Disorder and Pulmonary Tuberculosis Comorbidity Exacerbates Proinflammatory Immune Response—A Preliminary Study

Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-12-producing cells was similar between MDD-TB and TB patients. Likewise, MDD-TB and TB patients showed similar serum pro-inflammatory cytokine and chemokine levels, which were significantly lower than those in MDD patients. By multiple correspondence analyses, we observed that low levels of serum IL-4, IL-10, and IL-13 were powerfully associated with TB comorbidities with MDD. A high frequency of IFN-γ-producing cells is associated with low levels of serum anti-inflammatory cytokines in MDD-TB patients.

Trypanosoma cruzi Isolates Naturally Adapted to Congenital Transmission Display a Unique Strategy of Transplacental Passage.

Chagas disease is mainly transmitted by vertical transmission (VT) in nonendemic areas and in endemic areas where vector control programs have been successful. For the present study, we isolated natural Trypanosoma cruzi strains vertically transmitted through three generations and proceeded to study their molecular mechanism of VT using mice. No parasitemia was detected in immunocompetent mice, but the parasites were able to induce an immune response and colonize different organs. VT experiments revealed that infection with different strains did not affect mating, pregnancy, or resorption, but despite low parasitemia, VT strains reached the placenta and resulted in higher vertical transmission rates than strains of either moderate or high virulence. While the virulent strain modulated more than 2,500 placental genes, VT strains modulated 150, and only 29 genes are shared between them. VT strains downregulated genes associated with cell division and replication and upregulated immunomodulatory genes, leading to anti-inflammatory responses and tolerance. The virulent strain stimulated a strong proinflammatory immune response, and this molecular footprint correlated with histopathological analyses. We describe a unique placental response regarding the passage of T. cruzi VT isolates across the maternal-fetal interphase, challenging the current knowledge derived mainly from studies of laboratory-adapted or highly virulent strains. IMPORTANCE The main findings of this study are that we determined that there are Trypanosoma cruzi strains adapted to transplacental transmission and completely different from the commonly used laboratory reference strains. This implies a specific strategy for the vertical transmission of Chagas disease. It is impressive that the strains specialized for vertical transmission modify the gene expression of the placenta in a totally different way than the reference strains. In addition, we describe isolates of T. cruzi that cannot be transmitted transplacentally. Taken together, these results open up new insights into the molecular mechanisms of this insect vector-independent transmission form.

High-fat-diet induced obesity and diabetes mellitus in Th1 and Th2 biased mice strains: A brief overview and hypothesis.

Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide. Mice are commonly used to study the pathogenesis of these two conditions. Obesity and diabetes mellitus are induced by administering a high-fat diet in many studies although other diet-induced models are also used. Several factors may influence the outcome of the studies done to study diet-induced obesity in mice. The immune system plays a crucial role in the susceptibility of mice to develop obesity and metabolic disease. In this article, the reasons for differences in susceptibility to develop obesity and diabetes mellitus in mice in response to high-fat-diet feeding and the influence of immunological bias of the mice strain used in studies are evaluated. Mice strains that induce proinflammatory and Th1-type immune responses are found to be susceptible to high-fat-diet-induced obesity. A few studies which directly compared the effect of a high-fat diet on obesity and diabetic phenotype in Th1- and Th2-biased mice strains were briefly analyzed. Based on the observations, it is proposed that the liver and adipose tissue may respond differently to high-fat-diet feeding regimens in Th1- and Th2-biased mice strains. For instance, in Th1-biased mice, adipose tissue fat content was high both in the baseline as well as in response to a high-fat diet whereas in the liver, it was found to be less. It can be inferred that the immune responses to diet-induced models may provide insights into the pathogenesis of obesity and diabetes mellitus.

Cardiomyocyte infection by Trypanosoma cruzi promotes innate immune response and glycolysis activation.

Chagas cardiomyopathy, a disease caused by Trypanosoma cruzi (T. cruzi) infection, is a major contributor to heart failure in Latin America. There are significant gaps in our understanding of the mechanism for infection of human cardiomyocytes, the pathways activated during the acute phase of the disease, and the molecular changes that lead to the progression of cardiomyopathy. To investigate the effects of T. cruzi on human cardiomyocytes during infection, we infected induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) with the parasite and analyzed cellular, molecular, and metabolic responses at 3 hours, 24 hours, and 48 hours post infection (hpi) using transcriptomics (RNAseq), proteomics (LC-MS), and metabolomics (GC-MS and Seahorse) analyses. Analyses of multiomic data revealed that cardiomyocyte infection caused a rapid increase in genes and proteins related to activation innate and adaptive immune systems and pathways, including alpha and gamma interferons, HIF-1α signaling, and glycolysis. These responses resemble prototypic responses observed in pathogen-activated immune cells. Infection also caused an activation of glycolysis that was dependent on HIF-1α signaling. Using gene editing and pharmacological inhibitors, we found that T. cruzi uptake was mediated in part by the glucose-facilitated transporter GLUT4 and that the attenuation of glycolysis, HIF-1α activation, or GLUT4 expression decreased T. cruzi infection. In contrast, pre-activation of pro-inflammatory immune responses with LPS resulted in increased infection rates. These findings suggest that T. cruzi exploits a HIF-1α-dependent, cardiomyocyte-intrinsic stress-response activation of glycolysis to promote intracellular infection and replication. These chronic immuno-metabolic responses by cardiomyocytes promote dysfunction, cell death, and the emergence of cardiomyopathy.

Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice.

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool.

Molecular and immunological characterization of the calcyclin binding protein in rodent malaria parasite

Malaria remains as a global life-threatening disorder due to the emergence of resistance against standard antimalarials. Consequently, there is a serious need to better understand the biology of the malaria parasite in order to determine appropriate targets for new interventions. Calcyclin binding protein (CacyBP) is a multi-functional and multi-ligand protein that is not well characterized in malaria disease. In this study, we have cloned CacyBP from rodent species Plasmodium yoelii nigeriensis and purified the recombinant protein to carry out its detailed molecular, biophysical and immunological characterization. Molecular characterization indicates that PyCacyBP is a ∼27 kDa protein in parasite lysate and exists in monomer and dimer forms. Bioinformatic analysis of CacyBP showed significant sequence and structural similarities between rodent and human malaria parasites. CacyBP is expressed in all blood stages of P. yoelii nigeriensis parasite. In silico studies proposed the immunogenic potential of CacyBP. The rPyCacyBP immunized mice exhibited elevated levels of IgG1, IgG2a, IgG2b and IgG3 in their serum. Notably, cellular immune response in splenocytes from immunized mice showed increased expression of pro-inflammatory cytokines such as IL-12, IFN-γ and TNF-α. This CacyBP exhibited pro-inflammatory immune response in rodent host. These finding revealed that CacyBP may have the potential to boost the host immunity for protection against malaria infection. The present study provides basis for further exploration of the biological function of CacyBP in malaria parasite.

Use of sodium polyprenylphosphate to correct changes in the immune response caused by Helicobacter pylori CagA proteins in the experiment

Helicobacter pylori (HP) bacteria have a wide range of pathogenicity factors. The HP genome contains genes of the CagA group (cytotoxin-associated genes). Infection with CagA-positive HP strains is associated with the production of pro-inflammatory cytokines, which are involved in the maintenance and development of destructive and inflammatory changes in the organism. Here we studied the role of CagA proteins in the regulation of the immune response in DBA mice and evaluated the corrective effect of polyprenyl phosphate (PP) on this process. Genetically modified strains of E. coli were used, differing by the presence of an island of genes encoding the synthesis of HP CagA proteins. The drug Phosprenyl was used as a source of PP. The subpopulation composition of spleen cells was evaluated by flow cytofluorimetry using monoclonal antibodies. The level of IL 10, TGF-β in blood serum was determined by the enzyme immunoassay. The proliferative activity of splenocytes was measured by the standard procedure based on the inclusion of 3 H-thymidine in the DNA. CagA HP proteins caused the polarization of the immune response by the Th1-dominant type, which was expressed by an increase in the population of CD4 + cells, CD25 + and CD25 + Foxp3 + T cells and increase proliferation T- limphocytes. Inoculation of CagA + bacteria was accompanied by a quantitative increase in TGF-β produced by activated Treg cells. PP inoculation led to the normalization of the CD4 and CD8 T cells, a decrease in the populations of CD25 + , Foxp3 + , CD25 + Foxp3 + cells, and further increase in the IL-10 levels. Thus, PP corrected cellular immune response, prevented the pronounced polarization of the Th1 immune response, and reduced the activation of Treg population. The results obtained indicate a possible decrease in the pro-inflammatory immune response under the influence of PP.

Alterations in Lymphocytic Metabolism-An Emerging Hallmark of MS Pathophysiology?

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterised by acute inflammation and subsequent neuro-axonal degeneration resulting in progressive neurological impairment. Aberrant immune system activation in the periphery and subsequent lymphocyte migration to the CNS contribute to the pathophysiology. Recent research has identified metabolic dysfunction as an additional feature of MS. It is already well known that energy deficiency in neurons caused by impaired mitochondrial oxidative phosphorylation results in ionic imbalances that trigger degenerative pathways contributing to white and grey matter atrophy. However, metabolic dysfunction in MS appears to be more widespread than the CNS. This review focuses on recent research assessing the metabolism and mitochondrial function in peripheral immune cells of MS patients and lymphocytes isolated from murine models of MS. Emerging evidence suggests that pharmacological modulation of lymphocytic metabolism may regulate their subtype differentiation and rebalance pro- and anti-inflammatory functions. As such, further understanding of MS immunometabolism may aid the identification of novel treatments to specifically target proinflammatory immune responses.

The role of HMGB1 in COVID-19-induced cytokine storm and its potential therapeutic targets: A review.

Hyperinflammation characterized by elevated proinflammatory cytokines known as 'cytokine storms' is the major cause of high severity and mortality seen in COVID-19 patients. The pathology behind the cytokine storms is currently unknown. Increased HMGB1 levels in serum/plasma of COVID-19 patients were reported by many studies, which positively correlated with the level of proinflammatory cytokines. Dead cells following SARS-CoV-2 infection might release a large amount of HMGB1 and RNA of SARS-CoV-2 into extracellular space. HMGB1 is a well-known inflammatory mediator. Additionally, extracellular HMGB1 might interact with SARS-CoV-2 RNA because of its high capability to bind with a wide variety of molecules including nucleic acids and could trigger massive proinflammatory immune responses. This review aimed to critically explore the many possible pathways by which HMGB1-SARS-CoV-2 RNA complexes mediate proinflammatory responses in COVID-19. The contribution of these pathways to impair host immune responses against SARS-CoV-2 infection leading to a cytokine storm was also evaluated. Moreover, since blocking the HMGB1-SARS-CoV-2 RNA interaction might have therapeutic value, some of the HMGB1 antagonists have been reviewed. The HMGB1- SARS-CoV-2 RNA complexes might trigger endocytosis via RAGE which is linked to lysosomal rupture, PRRs activation, and pyroptotic death. High levels of the proinflammatory cytokines produced might suppress many immune cells leading to uncontrolled viral infection and cell damage with more HMGB1 released. Altogether these mechanisms might initiate a proinflammatory cycle leading to a cytokine storm. HMGB1 antagonists could be considered to give benefit in alleviating cytokine storms and serve as a potential candidate for COVID-19 therapy.

Differential regulation of lineage-determining transcription factor expression in innate lymphoid cell and adaptive T helper cell subsets.

CD4 T helper (Th) cell subsets, including Th1, Th2 and Th17 cells, and their innate counterparts innate lymphoid cell (ILC) subsets consisting of ILC1s, ILC2s and ILC3s, display similar effector cytokine-producing capabilities during pro-inflammatory immune responses. These lymphoid cell subsets utilize the same set of lineage-determining transcription factors (LDTFs) for their differentiation, development and functions. The distinct ontogeny and developmental niches between Th cells and ILCs indicate that they may adopt different external signals for the induction of LDTF during lineage commitment. Increasing evidence demonstrates that many conserved cis-regulatory elements at the gene loci of LDTFs are often preferentially utilized for the induction of LDTF expression during Th cell differentiation and ILC development at different stages. In this review, we discuss the functions of lineage-related cis-regulatory elements in inducing T-bet, GATA3 or RORγt expression based on the genetic evidence provided in recent publications. We also review and compare the upstream signals involved in LDTF induction in Th cells and ILCs both in vitro and in vivo. Finally, we discuss the possible mechanisms and physiological importance of regulating LDTF dynamic expression during ILC development and activation.

The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan.

Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2-dependent signaling, including activation of spleen tyrosine kinase, gene transcription, and tumor necrosis factor alpha (TNF-α) production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan, which leads to a proinflammatory immune response in the lung. IMPORTANCE Aspergillus fumigatus is a fungal pathogen that causes serious and often fatal disease in humans. The surface of Aspergillus is composed of complex sugar molecules. Recognition of these carbohydrates by immune cells by carbohydrate lectin receptors can lead to clearance of the infection or, in some cases, benefit the fungus by dampening the host response. Galactomannan is a carbohydrate that is part of the cell surface of Aspergillus but is also released during infection and is found in patient lungs as well as their bloodstreams. The significance of our research is that we have identified Dectin-2 as a mammalian immune cell receptor that recognizes, binds, and signals in response to galactomannan. These results enhance our understanding of how this carbohydrate interacts with the immune system at the site of infection and will lead to broader understanding of how release of galactomannan by Aspergillus effects the immune response in infected patients.

Nutritional and Functional Properties of Novel Italian Spray-Dried Cricket Powder.

Insects, especially crickets, have been proposed as a novel source of nutrients in human nutrition since they possess bioactive molecules, including high protein content, lipids, chitin, vitamins and minerals. In this work, the nutritional and functional properties of a novel Italian spray-dried (SD) cricket powder were evaluated. The powder was characterized by physico-chemical properties (morphology, size distribution, solid state, thermal profiles, and surface zeta potential), and antioxidant properties. Moreover, preclinical properties (cytocompatibility and pro-inflammatory immune response) were assessed. The powder was characterized by microparticle structure with bulges and rough surfaces, showing distinctive antioxidant properties. The preclinical results suggested that the SD crickets were biocompatible towards Caco-2 and macrophages without immune response, representing an interesting material for the food industry that could provide health benefits in addition to the basic nutritional value of traditional foods.

Synthesis and immunopharmacological evaluation of novel TLR7 agonistic triazole tethered imidazoquinolines.

Toll-like receptors-7 and -8 are expressed abundantly on antigen-presenting cells, and their agonists make potential adjuvant candidates for the development of new efficacious vaccines. In view of the importance of new efficacious imidazoquinoline based adjuvants, herein we have synthesized a focused library of a new class of imidazoquinolines retaining the N-isobutyl substitution of an imidazole moiety as in imiquimod and introduced a 1,2,3-triazolyl moiety upon alkyl substitution at the imidazolemethyne carbon employing triazolyl click chemistry. All the novel analogues were characterized using various spectroscopic techniques and the target specificity of these molecules was determined using HEK TLR7/8 transfected cell lines. TLR7/8 activity and also the molecular docking results correlated primarily to the position of the substituent for aromatic groups and also to the chain length in alkyl substitutions. The immunomodulatory properties of these analogues were evaluated using murine DC activation and also with hPBMC activation markers, cytokines which revealed that these analogues after modification were able to target the TLR7 receptors and also had a pro-inflammatory immune response.

Single-tailed heterocyclic carboxamide lipids for macrophage immune-modulation.

The discovery of new immune-modulating biomaterials is of significant value to immuno-engineering and therapy development. Here, we discovered that single-tailed heterocyclic carboxamide lipids preferentially modulated macrophages - but not dendritic cells - by interfering with sphingosine-1-phosphate-related pathways, consequently increasing interferon alpha expression. We further performed extensive downstream correlation analysis and determined key factors in physicochemical properties likely to modulate pro-inflammatory and anti-inflammatory immune responses. These properties will be useful for the rational design of the next generation of cell type-specific immune-modulating lipids.

Kinetics of interferon-λ and receptor expression in response to in vitro respiratory viral infection.

The major protective immune response against viruses is the production of type Iand III interferons (IFNs). IFNs induce the expression of hundreds of IFN-stimulated genes (ISGs) that block viral replication and further viral spread. In this report, we analyzed the expression of IFNs and some ISGs (MxA, PKR, OAS-1, IFIT-1, RIG-1, MDA5, SOCS-1) in alveolar epithelial cells (A549) in response to infection with influenza Aviruses (A/California/07/09 (H1N1pdm); A/Texas/50/12 (H3N2)); influenza Bvirus (B/Phuket/3073/13); adenovirus type 5 and 6; or respiratory syncytial virus (strain A2). Influenza Bvirus had the ability to most rapidly induce IFNs and ISGs as well as to stimulate excessive IFN-α, IFN-β and IFN-λ secretion. It seems curious that IAV H1N1pdm did not induce IFN-λ secretion, but enhanced type IIFN and interleukin (IL)-6 production. We emphasized the importance of the negative regulation of virus-triggered signaling and cellular IFN response. We showed adecrease in IFNLR1 mRNA in the case of IBV infection. The attenuation of SOCS-1 expression in IAV H1N1pdm can be considered as the inability of the system to restore the immune status. Presumably, the lack of negative feedback loop regulation of proinflammatory immune response may be afactor contributing to the particular pathogenicity of several strains of influenza. Keywords: lambda interferons; MxA; influenza; respiratory syncytial virus; A549 cells.

Эпигенетика и программирование целиакии

Global trends in the increasing prevalence of celiac disease in recent decades have raised questions about the possible mechanisms underlying the development of this disease. Genetic markers of predisposition to celiac disease, particularly HLADQ2/8, are well known. These haplotypes are detected in about 40% of the population, but celiac disease develops in 1–2% of people who are genetically predisposed. The presence of genetic predisposition and the consumption of gluten-containing foods are not enough to develop the disease. Co-factors may include impaired intestinal barrier function, pro-inflammatory immune response to gluten, and microbiome imbalance. Possible predisposing factors are epigenetic mechanisms: methylation and acetylation of DNA and histone, as well as microRNAs, which are associated with dietary patterns and act antenatally and throughout life. Understanding these factors is important for proper treatment tactics and disease prevention. Key words: celiac disease, genetics, epigenetics, nutrition, microbiota, inflammation

Fibroblast ferroptosis is involved in periodontitis-induced tissue damage and bone loss.

Periodontitis causes inflammatory destructions of tooth-supporting tissue and constitutes a significant burden on public health. Failing to reserve the tissue damage and bone loss by any of the currently available therapies has left periodontitis uncurable thus far. Understanding the molecular mechanism in the inflammatory process is crucial to elucidating the pathogenesis and enlightening new therapeutic strategies for periodontitis. This study was to investigate whether and how ferroptosis, a newly-discovered form of cell death, was involved in the pathogenesis of periodontitis. Healthy and periodontitis human gingiva samples were collected and ligature-induced periodontitis murine models were constructed to investigate the role of ferroptosis in periodontitis. Single-cell RNA sequencing data was analyzed to identify the cell type that underwent ferroptosis. The susceptibility of human gingival fibroblasts to ferroptosis was investigated by in vitro cell cultures. We found that gingival fibroblasts undergo ferroptosis in periodontitis, and that periodontitis-induced tissue damage and bone loss were alleviated by inhibition of ferroptosis. Periodontitis-induced pro-inflammatory immune responses was featured by profound elevation of fibroblast-derived Interleukin-6, which was attenuated by ferroptosis inhibition. These results indicated fibroblast ferroptosis as a new clue to unveiling the cellular and molecular basis for periodontitis-induced tissue damage. Involvement of ferroptosis/Interleukin-6 signaling in the pathogenic process suggested a potential target for immunopharmacological approaches to curing periodontitis.

Focus on host/organ unregulated response: a common cause of critical illness.

Focus on host/organ unregulated response: a common cause of critical illness.