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Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been identified as part of polytrauma patients' sterile inflammatory response. This systematic review aimed to determine the clinical significance of NETs in polytrauma, focusing on potential prognostic, diagnostic and therapeutic relevance. The methodology covered all major databases and all study types, but was restricted to polytraumatised humans. Fourteen studies met the inclusion criteria, reporting on 1967 patients. Ten samples were taken from plasma and four from whole blood. There was no standardisation of methodology of NET detection among plasma studies; however, of all the papers that included a healthy control NET, proxies were increased. Polytrauma patients were consistently reported to have higher concentrations of NET markers in peripheral blood than those in healthy controls, but their diagnostic, therapeutic and prognostic utility is equivocal due to the diverse study population and methodology. After 20 years since the discovery of NETs, their natural history and potential clinical utility in polytrauma is undetermined, requiring further standardisation and research. [ABSTRACT FROM AUTHOR]

Simple Summary: Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in the circulation of patients with cancer, sepsis or chronic inflammation, modulate the immune response against cancer (favoring tumor onset and progression) and promote neoangiogenesis. These premises suggest that MDSCs could be involved in the pathogenesis of primary myelofibrosis (PMF) (a myeloproliferative neoplasm characterized by chronic inflammation and extensive neoangiogenesis in bone marrow and spleen). In this paper, we found that (1) MDSCs are increased both in the circulation and in the spleen of PMF patients and strongly correlate with disease progression; and (2) reduced CXCR4 expression on MDSCs along with increased plasmatic SDF-1α can be involved in their mobilization. These findings suggest that circulating MDSCs can be considered a parameter of disease severity and set MDSCs as potential new targets for cancer therapy. Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by a chronic inflammatory state that plays a relevant role in the disease pathogenesis (as proven by high levels of inflammatory cytokines with prognostic significance and by a persistent oxidative stress) and by extensive neoangiogenesis in bone marrow (BM) and spleen. Myeloid-derived suppressor cells (MDSCs) are immature cells that expand in patients with cancer, sepsis or chronic inflammation, favoring tumor onset and progression mainly through the decrease in immune surveillance and the promotion of neoangiogenesis. In this paper, we evaluated the presence of circulating MDSCs in PMF patients, the plasmatic factors involved in their mobilization/expansion and the correlations with laboratory, genetic and clinical parameters. The data indicated that MDSCs could have a relevant role in PMF as a new pathogenic mechanism contributing to explaining the phenotypic diversity observed during the clinical course of the disease, or a potential new target for personalized treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Achieving improved rates of overall survival remains a significant challenge in advanced-stage ovarian cancer; even if complete debulking is achieved, certain patients report poor results in terms of survival. Therefore, the aim of this paper is to investigate new prognostic markers that could point out which cases could benefit most from debulking surgery and which ones should be rather submitted to neoadjuvant therapies followed by debulking surgery. Background: Despite improving surgical techniques and achieving more often complete debulking procedures, certain patients with advanced-stage ovarian cancer still have a very poor prognosis. The aim of the current paper is to investigate whether inflammatory and nutritional status can predict the long-term outcomes of ovarian cancer patients. Methods: A retrospective analysis of 57 cases diagnosed with advanced-stage ovarian cancer submitted to surgery as first intent therapy was carried out. In all cases, the preoperative status was determined by calculating the CRP/albumin ratio, as well as the Glasgow score, the modified Glasgow score and the prognostic nutritional index. Results: Patients presenting higher values of the CRP/albumin ratio, with a higher Glasgow score, modified Glasgow score and prognostic nutritional index (PNI), were more frequently associated with incomplete debulking surgery, a higher peritoneal carcinomatosis index and poorer overall survival (20 months versus 9 months for the CRP/albumin ratio p = 0.011, 42 versus 27 versus 12 months for the Glasgow score p = 0.042, 50 versus 19 versus 12 months for the modified Glasgow score, p = 0.001, and 54 months versus 21 months, p = 0.011 for the prognostic nutritional index). Conclusions: A strong relationship between the nutritional and inflammatory status in advanced-stage ovarian cancer seems to exist. [ABSTRACT FROM AUTHOR]

Simple Summary: Feline chronic gingivostomatitis (FCGS) remains a poorly understood clinical condition with significant impact on the quality of life of affected cats. An understanding of the pathogenesis of this inflammatory disease will enable the development of improved and targeted therapeutics beyond full-mouth extractions. Here, we collected sterile noninvasive plaque samples at ten distinct sites within the oral cavity in cats with FCGS (n = 12), healthy cats (n = 9), or cats with other oral conditions (n = 11). We used 16S rRNA gene sequencing (V1–V9) to profile bacteria in the oral microbiome. We found that the microbiomes of cats with FCGS were distinct from those of healthy cats at multiple oral sites, indicating that dysbiosis is present throughout the oral cavity. The microbiomes of cats varied depending on their oral diagnoses, confirming that the various dental diseases impact the microbiome in different ways. Lastly, microbiome data obtained from swabs of the oral cavity were similar to those obtained using endodontic paper point plaque samples, suggesting this approach as another valuable method of sampling. Given these additional insights, future studies can focus on targeted therapeutics so that extraction of healthy teeth will no longer be the standard of care for this challenging condition. Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis (n = 12), healthy cats (n = 9), and cats with tooth resorption or periodontitis (n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method. Collectively, our work furthers our understanding of the dysbiosis and composition of bacteria in the oral microbiome in FCGS, with hopes of contributing to the prevention, diagnosis, and treatment of this challenging condition in felines. [ABSTRACT FROM AUTHOR]

Sleep bruxism (SB) is a sleep-related behavior characterized as rhythmic (phasic) or non-rhythmic (tonic) masticatory muscle activity. SB is a common sleep behavior with a predominantly central origin. The aim of this systematic review was to evaluate the relationship between inflammatory status and SB according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020). The research was registered at PROSPERO (CRD42023395985). We performed a systematic literature analysis using five different databases. Furthermore, the backward snowballing technique was applied to identify additional papers. Initially, 28 papers were screened from the database search, and 162 papers were revealed in the backward snowballing process. Eventually, five articles were included. Data concerning the inflammatory status of patients experiencing SB were investigated and summarized. Due to the heterogeneity of the compared studies, only a qualitative comparison and narrative summary were performed. The results suggest that SB could be associated with systemic inflammation. In fact, this systematic review revealed that there are no papers conclusively showing that the inflammatory status in bruxers is comparable to non-bruxers. However, each of the examined studies utilized different methods of assessing systemic inflammation, which makes the results dubious. [ABSTRACT FROM AUTHOR]

This paper delves into the diverse and significant roles of curcumin, a polyphenolic compound from the Curcuma longa plant, in the context of cancer and inflammatory diseases. Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research comprehensively investigates curcumin's molecular interactions with key proteins involved in cancer progression and the inflammatory response, primarily through molecular docking studies. In cancer, curcumin's effectiveness is determined by examining its interaction with pivotal proteins like CDK2, CK2α, GSK3β, DYRK2, and EGFR, among others. These interactions suggest curcumin's potential role in impeding cancer cell proliferation and survival. Additionally, the paper highlights curcumin's impact on inflammation by examining its influence on proteins such as COX-2, CRP, PDE4, and MD-2, which are central to the inflammatory pathway. In vitro and clinical studies are extensively reviewed, shedding light on curcumin's binding mechanisms, pharmacological impacts, and therapeutic application in various cancers and inflammatory conditions. These studies are pivotal in understanding curcumin's functionality and its potential as a therapeutic agent. Conclusively, this review emphasizes the therapeutic promise of curcumin in treating a wide range of health issues, attributed to its complex chemistry and broad pharmacological properties. The research points towards curcumin's growing importance as a multi-faceted natural compound in the medical and scientific community. [ABSTRACT FROM AUTHOR]

Simple Summary: Photodynamic therapy (PDT) is a cancer treatment that uses photogenerated reactive oxygen species (ROS) to damage target cells. The unique mechanism of action of PDT involves the systemic or local administration of a photosensitizing compound (photosensitizer), which is then activated by light of a specific energy. PDT induces a very strong local inflammatory response. A number of adaptive mechanisms are induced within the tumor, related to increased amino acid metabolism and damage to lymphatic vessels. In this review, we are describing the adaptive immune response induced by ROS and generated by PDT. Cancer is one of the most significant causes of death worldwide. Despite the rapid development of modern forms of therapy, results are still unsatisfactory. The prognosis is further worsened by the ability of cancer cells to metastasize. Thus, more effective forms of therapy, such as photodynamic therapy, are constantly being developed. The photodynamic therapeutic regimen involves administering a photosensitizer that selectively accumulates in tumor cells or is present in tumor vasculature prior to irradiation with light at a wavelength corresponding to the photosensitizer absorbance, leading to the generation of reactive oxygen species. Reactive oxygen species are responsible for the direct and indirect destruction of cancer cells. Photodynamically induced local inflammation has been shown to have the ability to activate an adaptive immune system response resulting in the destruction of tumor lesions and the creation of an immune memory. This paper focuses on presenting the latest scientific reports on the specific immune response activated by photodynamic therapy. We present newly discovered mechanisms for the induction of the adaptive response by analyzing its various stages, and the possible difficulties in generating it. We also present the results of research over the past 10 years that have focused on improving the immunological efficacy of photodynamic therapy for improved cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is still one of the deadliest malignancies affecting women worldwide which is associated with poor long-term outcomes even in certain cases in which complete debulking is achieved. In this respect, attention has been focused on identifying other prognostic factors which might indicate which cases are expected to have the best long-term outcomes such as the procoagulant or inflammatory status. The aim of the current paper is to analyse the correlation between the most frequently cited inflammatory and tumoral markers and the long-term outcomes of ovarian cancer patients. Ovarian cancer remains one of the most lethal gynaecological malignancies affecting women worldwide; therefore, attention has been focused on identifying new prognostic factors which might help the clinician to select cases who could benefit most from surgery versus cases in which neoadjuvant systemic therapy followed by interval debulking surgery should be performed. The aim of the current paper is to identify whether preoperative inflammation could serve as a prognostic factor for advanced-stage ovarian cancer. Material and methods: The data of 57 patients who underwent to surgery for advanced-stage ovarian cancer between 2014 and 2020 at the Cantacuzino Clinical Hospital were retrospectively reviewed. The receiver operating characteristic curve was used to determine the optimal cut-off value of different inflammatory markers for the overall survival analysis. The analysed parameters were the preoperative level of CA125, monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII). Results: Baseline CA125 > 780 µ/mL, NLR ≥ 2.7, MLR > 0.25, PLR > 200 and a systemic immune inflammation index (SII, defined as platelet × neutrophil–lymphocyte ratio) ≥ 84,1000 were associated with significantly worse disease-free and overall survival in a univariate analysis. In a multivariate analysis, MLR and SII were significantly associated with higher values of overall survival (p < 0.0001 and p = 0.0124); meanwhile, preoperative values of CA125, PLR and MLR were not associated with the overall survival values (p = 0.5612, p = 0.6137 and p = 0.1982, respectively). In conclusion, patients presenting higher levels of MLR and SII preoperatively are expected to have a poorer outcome even if complete debulking surgery is performed and should be instead considered candidates for neoadjuvant systemic therapy followed by interval surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the issue of metastatic endometrial cancer (EC), which significantly impacts treatment success and overall survival rates. The study explores various factors contributing to metastasis, including the molecular profile of EC, hormone activity (like estrogen and prolactin), and pro-inflammatory adipocytokines. It also investigates how altered microRNA expression affects gene regulation linked to the dissemination of the cancer. The paper highlights the importance of imaging techniques, particularly transvaginal ultrasound with tumor-free distance (uTFD), in detecting metastases. Additionally, it discusses how diagnostic and therapeutic methods can influence the spread of EC, with hysteroscopy potentially increasing risk in advanced stages and laparoscopic hysterectomy being safer if performed with care. This research could improve our understanding of EC and guide better diagnostic and treatment strategies. The presence of metastatic endometrial cancer (EC) is a key problem in treatment failure associated with reduced overall survival rates. The most common metastatic location is the pelvic lymph nodes, and the least common is the brain. The presence of metastasis depends on many factors, including the molecular profile of cancer (according to the TCGA—Genome Atlas), the activity of certain hormones (estrogen, prolactin), and pro-inflammatory adipocytokines. Additionally, an altered expression of microRNAs affecting the regulation of numerous genes is also related to the spread of cancer. This paper also discusses the value of imaging methods in detecting metastases; the primary role is attributed to the standard transvaginal USG with the tumor-free distance (uTFD) option. The influence of diagnostic and therapeutic methods on EC spread is also described. Hysteroscopy, according to the analysis discussed above, may increase the risk of metastases through a fluid medium, mainly performed in advanced stages of EC. According to another analysis, laparoscopic hysterectomy performed with particular attention to avoiding risky procedures (trocar flushing, tissue traumatization, preserving a margin of normal tissue) was not found to increase the risk of EC dissemination. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 ( n - 6) PUFAs and low levels of omega-3 ( n - 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of n - 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.

Neuroblastoma is the most common extracranial solid tumor in children. It is a highly heterogeneous tumor consisting of different subcellular types and genetic abnormalities. Literature data confirm the biological and clinical complexity of this cancer, which requires a wider availability of gene targets for the implementation of personalized therapy. This paper presents a study of neuroblastoma samples from primary tumors of untreated patients. The focus of this analysis is to evaluate the impact that the inflammatory process may have on the pathogenesis of neuroblastoma. Eighty-eight gene profiles were selected and analyzed using a non-negative matrix factorization framework to extract a subset of genes relevant to the identification of an inflammatory phenotype, whose targets ( PIK3CG , NFATC2 , PIK3R2 , VAV1 , RAC2 , COL6A2 , COL6A3 , COL12A1 , COL14A1 , ITGAL , ITGB7 , FOS , PTGS2 , PTPRC , ITPR3 ) allow further investigation. Based on the genetic signals automatically derived from the data used, neuroblastoma could be classified according to stage rather than as a "cold" or "poorly immunogenic" tumor.

Air pollution poses a significant global health risk, with fine particulate matter (PM 2.5 ) such as diesel exhaust particles (DEPs) being of particular concern due to their potential to drive systemic toxicities through bloodstream infiltration. The association between PM 2.5 exposure and an increased prevalence of metabolic disorders, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), is evident against a backdrop of rising global obesity and poor metabolic health. This paper examines the role of adipose tissue in mediating the effects of PM 2.5 on metabolic health. Adipose tissue, beyond its energy storage function, is responsive to inhaled noxious stimuli, thus disrupting metabolic homeostasis and responding to particulate exposure with pro-inflammatory cytokine release, contributing to systemic inflammation. The purpose of this study was to characterize the metabolic response of adipose tissue in mice exposed to either DEPs or room air (RA), exploring both the adipokine profile and mitochondrial bioenergetics. In addition to a slight change in fat mass and a robust shift in adipocyte hypertrophy in the DEP-exposed animals, we found significant changes in adipose mitochondrial bioenergetics. Furthermore, the DEP-exposed animals had a significantly higher expression of adipose inflammatory markers compared with the adipose from RA-exposed mice. Despite the nearly exclusive focus on dietary factors in an effort to better understand metabolic health, these results highlight the novel role of environmental factors that may contribute to the growing global burden of poor metabolic health.

Inflammation is activated by diverse triggers that induce the expression of cytokines and adhesion molecules, which permit a succession of molecules and cells to deliver stimuli and functions that help the immune system clear the primary cause of tissue damage, whether this is an infection, a tumor, or a trauma. During inflammation, short-term changes in the expression and secretion of strong mediators of inflammation occur, while long-term changes occur to specific groups of cells. Long-term changes include cellular transdifferentiation for some types of cells that need to regenerate damaged tissue, as well as death for specific immune cells that can be detrimental to tissue integrity if they remain active beyond the boundaries of essential function. The transcriptional regulator NFκB enables some of the fundamental gene expression changes during inflammation, as well as during tissue development. During recurrence of malignant disease, cell stress-induced alterations enable the growth of cancer cell clones that are substantially resistant to therapeutic intervention and to the immune system. A number of those alterations occur due to significant defects in feedback signal cascades that control the activity of NFκB. Specifically, cell stress contributes to feedback defects as it overrides modules that otherwise control inflammation to protect host tissue. NFκB is involved in both the suppression and promotion of cancer, and the key distinctive feature that determines its net effect remains unclear. This paper aims to provide a clear answer to at least one aspect of this question, namely the mechanism that enables a divergent response of cancer cells to critical inflammatory stimuli and to cell stress in general. [ABSTRACT FROM AUTHOR]

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-β) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-β activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs. [ABSTRACT FROM AUTHOR]

Featured Application: Utilization of Rosmarinus officinalis extracts and/or its bioactives as ingredients in functional products, foods, cosmetics, and pharmaceuticals, with anti-inflammatory health-promoting neuroprotective effects against inflammation-related neurodegenerative disorders, such as Alzheimer's and Parkinson's Diseases. Neurodegenerative disorders (NDs) are conditions marked by progressively escalating inflammation that leads to the degeneration of neuronal structure and function. There is an increasing interest in natural compounds, especially those from pharmaceutical plants, with neuroprotective properties as part of potential therapeutic interventions. Thus, the rich bioactive content of the perennial herb rosemary (Rosmarinus officinalis) is thoroughly reviewed in this article, with an emphasis on its pleiotropic pharmacological properties, including its antioxidant, anti-inflammatory, and neuroprotective health-promoting effects. In addition, a comprehensive analysis of the existing scientific literature on the potential use of rosemary and its bioactive constituents in treating neurodegenerative disorders was also conducted. Rosemary and its bioactives' chemical properties and neuroprotective mechanisms are discussed, focusing on their ability to mitigate oxidative stress, reduce inflammation, and modulate neurotransmitter activity. The role of rosemary in enhancing cognitive function, attenuating neuronal apoptosis, and promoting neurogenesis is outlined. Key bioactive components, such as rosmarinic acid and carnosic acid, are also highlighted for their neuroprotective act. The promising outcomes of the conducted pre-clinical studies or clinical trials confirm the efficacy of rosemary in preventing or alleviating Alzheimer's and Parkinson's diseases both in vitro (in cells) and in vivo (in animal models of NDs). From this perspective, the applications of rosemary's bio-functional compounds and extracts in the food, cosmetics, and pharmaceutical sectors are also presented; in the latter, we discuss their use against neurodegenerative disorders, either alone or as adjuvant therapies. This paper critically evaluates these studies' methodological approaches and outcomes, providing insights into the current state of the clinical research and identifying potential avenues for future investigation. All findings presented herein contribute to the growing body of literature and support the exploration of natural compounds as promising candidates for novel applications and neuroprotective interventions, paving the way for more applied scientific research. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is an immune-mediated chronic disorder associated with various comorbidities. Even though biologics and small-molecule inhibitors are the mainstay treatment for moderate-to-severe psoriasis, there is no current consensus regarding which agent should be used for a specific type of patient. This paper aims to test the reliability of blood-count-derived inflammatory markers in assessing treatment response to biologics and small-molecule inhibitors in psoriasis. Material and Methods: Bio-naïve adult patients diagnosed with chronic plaque psoriasis fulfilling the inclusion criteria were enrolled. They were divided into study subgroups based on treatment of choice, and blood-count-derived inflammatory markers were analyzed at baseline, three-month, six-month, and at twelve-month visits. Results: A total of 240 patients were included. The highest number of patients underwent treatment with ixekizumab. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-monocyte ratio (PMR), monocyte-to-lymphocyte ratio (MLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), and aggregate index of systemic inflammation (AISI) all varied significantly (p < 0.005) between the four visits. The psoriasis area severity index (PASI) score correlated with PLR, d-NLR, and SII, while the psoriasis scalp severity index (PSSI) score correlated with AISI and SIRI. More than half of patients reached the target goal of PASI90 at the six-month visit. A total of 77 patients were super-responders, with the highest number undergoing treatment with ixekizumab. Higher baseline values of d-NLR and SIRI are independent predictors of the super-responder status. Conclusions: Blood-count-derived inflammatory markers can serve as indicators of treatment response to biologics in psoriasis, while d-NLR and SIRI were independent predictors of super-responders in our study. [ABSTRACT FROM AUTHOR]

Simple Summary: This review explores the emerging area of the prognostic significance and therapeutic implications of inflammation-based scores in Hepatocellular carcinoma (HCC). Through comprehensive analysis and synthesis of existing literature, the paper highlights the prognostic value of these scores in predicting survival outcomes, recurrence, and treatment response in HCC patients. Furthermore, it discusses the underlying mechanisms linking inflammation with HCC progression and explores potential implications for personalized therapeutic strategies. Overall, this review underscores the importance of integrating inflammation-based scores into clinical practice for better risk stratification and management of HCC patients. Hepatocellular carcinoma (HCC) is the most common primary liver cancer, posing a significant global health challenge with an increasing incidence. In recent years, multiple staging systems and scores have been proposed, emphasising the necessity for the development of precise prognostic tools. The well-documented etiological relationship between chronic inflammation and carcinogenesis has prompted researchers to explore novel prognostic markers associated with the inflammatory status of HCC patients. This review summarises the current data about inflammation-based scores in the context of HCC. We discuss established scores like the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and the neutrophil-to-lymphocyte ratio (NLR) and others not as extensively studied, examining their utility in predicting survival outcomes and treatment response in HCC patients. Furthermore, we explore emerging scores, including the prognostic nutritional index (PNI) and other lymphocyte-based scores, assessing their potential in refining risk stratification and guiding therapeutic decisions in the era of precision medicine. As research progresses and these scores undergo further refinement and integration into the evolving landscape of HCC management, they carry significant potential for improving patient outcomes. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide with coronary artery disease (CAD) being the first culprit in this group. In terms of CAD, not only its presence but also its severity plays a role in the patient's treatment and prognosis. CAD complexity can be assessed with the indicator named the SYNTAX score (SS). A higher SS is associated with major adverse cardiovascular event (MACE) occurrence in short- and long-term observations. Hence, the risk factors affecting CAD severity based on SS results may help lower the risk among patients with already developed CAD to reduce their impact on coronary atherosclerosis progression. The well-established risk factors of CAD are consistent with those associated with the coronary plaque burden. However, recently, it was shown that new indicators exist, which we present in this paper, that significantly contribute to CAD complexity such as inflammatory parameters, C-reactive protein (CRP), ratios based on blood smear results, and uric acid. Moreover, microbiota alteration, vitamin D deficiency, and obstructive sleep apnea (OSA) also predicted CAD severity. However, sometimes, certain indicators were revealed as significant only in terms of chronic coronary syndromes (CCSs) or specific acute coronary syndromes (ACSs). Importantly, there is a need to apply the interdisciplinary and translational approach to the novel CAD severity risk assessment to maximize the impact of secondary prevention among patients at risk of coronary atherosclerosis progression. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) of the knee is a prevalent cause of chronic pain and disability, particularly affecting women. While traditionally attributed to chronic wear and tear, recent evidence highlights multifactorial pathogenesis involving low-grade inflammation and neoangiogenesis. Current therapeutic options include physical therapy, pharmacotherapy, and total knee arthroplasty (TKA). However, a subset of patients remain symptomatic despite conservative measures, necessitating the development of minimally invasive interventions. Genicular artery embolization (GAE) emerges as a promising option, targeting neovascularization and inflammatory processes in OA. This paper reviews the pathophysiological basis, patient selection criteria, procedural details, and outcomes of GAE. Notably, GAE demonstrates efficacy in relieving knee pain and improving function in patients refractory to conventional therapy. While further research is warranted to elucidate its long-term outcomes and compare it with existing modalities, GAE represents a novel approach in the management of symptomatic knee OA, potentially delaying or obviating the need for surgical intervention. Here, we synthesize the relevant literature, technical details of the procedure, and future perspectives. Moreover, the success of GAE prompts the exploration of transarterial embolization in other musculoskeletal conditions, underscoring the evolving role of interventional radiology in personalized pain management strategies. [ABSTRACT FROM AUTHOR]

The resolution of inflammation is the primary domain of specialised pro-resolving mediators (SPMs), which include resolvins, protectins, and their forms synthesised under the influence of aspirin and the maresins. The role of these SPMs has been discussed by many authors in the literature, with particular reference to neuroinflammation and significant neurological disorders. This review discusses the role of G protein-coupled receptor 18 (GPR18), resolvin D2 (RvD2) activity, and the GPR18-RvD2 signalling axis, as well as the role of small molecule ligands of GPR18 in inflammation in various health disorders (brain injuries, neuropathic pain, neurodegenerative/cardiometabolic/cardiovascular/gastrointestinal diseases, peritonitis, periodontitis, asthma and lung inflammation, Duchenne muscular dystrophy, SARS-CoV-2-induced inflammation, and placenta disorders. The idea of biological intervention through modulating GPR18 signalling is attracting growing attention because of its great therapeutic potential. With this paper, we aimed to present a comprehensive review of the most recent literature, perform a constructive view of data, and point out research gaps.

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with metabolic syndrome exhibit simultaneously pro-thrombotic and a pro-inflammatory conditions which more probably can lead to cardiovascular disease progression, type 2 diabetes mellitus, and some types of cancer. The present scoping review is aimed at highlighting any relations between cancer risk, inflammation, and metabolic syndrome. A total of 20 manuscripts were identified and, among them, we identified some associations with breast cancer, colorectal cancer, esophageal adenocarcinoma, hepatocellular carcinoma (HCC), and cancer in general. Therefore, it could be deducted that cancer and its related progression may also depend on a latent chronic inflammatory condition associated with other concomitant conditions, including type 2 diabetes mellitus, metabolic syndrome, and obesity. Therefore, prevention may potentially help individuals to protect themselves from cancer. Background: Individuals with metabolic syndrome exhibit simultaneously pro-thrombotic and pro-inflammatory conditions which more probably can lead to cardiovascular diseases progression, type 2 diabetes mellitus, and some types of cancer. The present scoping review is aimed at highlighting the association between cancer risk, inflammation, and metabolic syndrome. Methods: A search strategy was performed, mixing keywords and MeSH terms, such as "Cancer Risk", "Inflammation", "Metabolic Syndrome", "Oncogenesis", and "Oxidative Stress", and matching them through Boolean operators. A total of 20 manuscripts were screened for the present study. Among the selected papers, we identified some associations with breast cancer, colorectal cancer, esophageal adenocarcinoma, hepatocellular carcinoma (HCC), and cancer in general. Conclusions: Cancer and its related progression may also depend also on a latent chronic inflammatory condition associated with other concomitant conditions, including type 2 diabetes mellitus, metabolic syndrome, and obesity. Therefore, prevention may potentially help individuals to protect themselves from cancer. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It is estimated that 537 million people have DM, but the condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, the number of DM cases is steadily increasing. The state of chronic hyperglycaemia in the body leads to numerous complications, including diabetic cardiomyopathy (DCM). A number of pathophysiological mechanisms are behind the development and progression of cardiomyopathy, including increased oxidative stress, chronic inflammation, increased synthesis of advanced glycation products and overexpression of the biosynthetic pathway of certain compounds, such as hexosamine. There is extensive research on the treatment of DCM, and there are a number of therapies that can stop the development of this complication. Among the compounds used to treat DCM are antiglycaemic drugs, hypoglycaemic drugs and drugs used to treat myocardial failure. An important element in combating DCM that should be kept in mind is a healthy lifestyle—a well-balanced diet and physical activity. There is also a group of compounds—including coenzyme Q10, antioxidants and modulators of signalling pathways and inflammatory processes, among others—that are being researched continuously, and their introduction into routine therapies is likely to result in greater control and more effective treatment of DM in the future. This paper summarises the latest recommendations for lifestyle and pharmacological treatment of cardiomyopathy in patients with DM. [ABSTRACT FROM AUTHOR]

The Euganean Thermal District, situated in North-East Italy, is one of Europe's largest and oldest thermal centres. The topical application of its therapeutic thermal muds is recognised by the Italian Health System as a beneficial treatment for patients suffering from arthro-rheumatic diseases. Polysaccharides produced by the mud microbiota have been recently identified as anti-inflammatory bioactive molecules. In this paper we analysed the efficacy of Microbial-Polysaccharides (M-PS) derived from mature muds obtained at different maturation temperatures, both within and outside the codified traditional mud maturation range. M-PSs were extracted from six mature muds produced by five spas of the Euganean Thermal District and investigated for their chemical properties, monosaccharide composition and in vivo anti-inflammatory potential, using the zebrafish model organism. Additionally, mature muds were characterized for their microbiota composition using Next-Generation Sequencing. The results showed that all M-PSs exhibit similar anti-inflammatory potential, referable to their comparable chemical composition. This consistency was observed despite changes in cyanobacteria populations, suggesting a possible role of the entire microbial community in shaping the properties of these biomolecules. These findings highlight the importance of scientific research in untangling the origins of the therapeutic efficacy of Euganean Thermal muds in the treatment of chronic inflammatory conditions. [ABSTRACT FROM AUTHOR]

This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3. [ABSTRACT FROM AUTHOR]

The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization. [ABSTRACT FROM AUTHOR]

Crohn's disease, a chronic inflammatory process of the gastrointestinal tract defined by flares and periods of remission, is increasing in incidence. Despite advances in multimodal medical therapy, disease progression often necessitates multiple operations with high morbidity. The inability to treat Crohn's disease successfully is likely in part because the etiopathogenesis is not completely understood; however, recent research suggests the gut microbiome plays a critical role. How traditional perioperative management, including bowel preparation and preoperative antibiotics, further changes the microbiome and affects outcomes is not well described, especially in Crohn's patients, who are unique given their immunosuppression and baseline dysbiosis. This paper aims to outline current knowledge regarding perioperative management of Crohn's disease, the evolving role of gut dysbiosis, and how the microbiome can guide perioperative considerations with special attention to perioperative antibiotics as well as treatment of Mycobacterium avium subspecies paratuberculosis. In conclusion, dysbiosis is common in Crohn's patients and may be exacerbated by malnutrition, steroids, narcotic use, diarrhea, and perioperative antibiotics. Dysbiosis is also a major risk factor for anastomotic leak, and special consideration should be given to limiting factors that further perturb the gut microbiota in the perioperative period. [ABSTRACT FROM AUTHOR]

Inflammation is an essential contributor to various human diseases. Diosmetin (3′,5,7-trihydroxy-4′-methoxyflavone), a citrus flavonoid, can be used as an anti-inflammatory agent. All the information in this article was collected from various research papers from online scientific databases such as PubMed and Web of Science. These studies have demonstrated that diosmetin can slow down the progression of inflammation by inhibiting the production of inflammatory mediators through modulating related pathways, predominantly the nuclear factor-κB (NF-κB) signaling pathway. In this review, we discuss the anti-inflammatory properties of diosmetin in cellular and animal models of various inflammatory diseases for the first time. We have identified some deficiencies in current research and offer suggestions for further advancement. In conclusion, accumulating evidence so far suggests a very important role for diosmetin in the treatment of various inflammatory disorders and suggests it is a candidate worthy of in-depth investigation. [ABSTRACT FROM AUTHOR]

Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Several elements that are composed of, or related to, neutrophils, have been shown to inhibit strong immune responses to cancer and promote cancers' growth. This paper presents the collected data showing these elements and how their coordinated actions as an ensemble facilitate growth in the common cancers. The paper goes on to present a drug regimen, TICO, designed to reduce the cancer growth enhancing effects of the neutrophil related elements. TICO uses four already marketed, readily available generic drugs, repurposed to inhibit neutrophil centered growth facilitation of cancer. This paper presents remarkably uniform data showing that higher NLR is a robust prognostic indicator of shorter overall survival across the common metastatic cancers. Myeloid derived suppressor cells, the NLRP3 inflammasome, neutrophil extracellular traps, and absolute neutrophil count tend to all be directly related to the NLR. They, individually and as an ensemble, contribute to cancer growth and metastasis. The multidrug regimen presented in this paper, TICO, was designed to decrease the NLR with potential to also reduce the other neutrophil related elements favoring malignant growth. TICO is comprised of already marketed generic drugs: the phosphodiesterase 5 inhibitor tadalafil, used to treat inadequate erections; isotretinoin, the retinoid used for acne treatment; colchicine, a standard gout (podagra) treatment; and the common fish oil supplement omega-3 polyunsaturated fatty acids. These individually impose low side effect burdens. The drugs of TICO are old, cheap, well known, and available worldwide. They all have evidence of lowering the NLR or the growth contributing elements related to the NLR when clinically used in general medicine as reviewed in this paper. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of 'safe and effective' vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the 'safe and effective' narrative attached to these new technologies. Spike protein pathogenicity, termed 'spikeopathy', whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a 'synthetic virus', is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that 'spikeopathy' can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely. [ABSTRACT FROM AUTHOR]

The inflammatory potential of the diet, as measured by the Dietary Inflammatory Index (DII®), has been repeatedly shown to be associated with various inflammatory markers and mental and physical health outcomes. Of specific importance, several cross-sectional studies revealed mixed results regarding the correlations between the DII and sleep outcomes. Hence, in the current paper, a systematic review that examines the associations between the DII, sleep duration, and sleep quality was performed. The PubMed database was systematically searched for studies published up to November 2023 following PRISMA guidelines. Only cross-sectional studies that assessed the DII, sleep duration, and sleep quality across healthy and unhealthy cohorts were included. Eleven and seven studies were included in the systematic review for sleep quality and duration, respectively. The results of the present systematic review show that pro-inflammatory diets may be associated with poor sleep outcomes (duration and quality); however, as the current literature is inconsistent and limited, further cross-sectional studies in larger cohorts are necessary to (i) explore this relationship to address this heterogeneity and (ii) explore populations that are more sensitive to diet-induced inflammation. [ABSTRACT FROM AUTHOR]

Lannea L. genus belongs to the Anacardiaceae botanical family and has long been used in traditional medicinal systems of many countries to manage several health conditions, but no studies have been conducted regarding its usefulness as a source of herbal medicine for human use. A literature review was conducted on scientific papers indexed on B-On, Pubmed, and Web of Science databases. Our results showed that medicinal plants from this botanical genus, mostly constituted by bark and leaf, are often used to approach a wide variety of disease symptoms, like fever, inflammatory states, pain, and gastrointestinal disorders. Phytochemical profiles of Lannea species revealed that phenolic acid derivatives including hydroquinones, phenolic acids, flavonoids, condensed tannins, and triterpenoids are the main classes of secondary metabolites present. Among the total of 165 identified compounds, 57 (34.5%) are flavonoids, mostly quercetin- and myricetin-derived flavonols and catechin and epicatechin flavan-3-ol derivatives also containing a galloyl group. In vitro and in vivo studies allowed the identification of 12 different biological activities, amongst which antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities were the most frequently cited and observed in in vitro essays. Our review contributes useful information for the scientifical validation of the use of Lannea species in traditional medicinal systems and shows that more research needs to be conducted to better understand the concrete utility of these as herbal medicines. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the important role played by the lymphatic system in tissue drainage, metabolism, water–salt metabolism, and its protective compensatory and immune functions, it is important to further study the role of the lymphatic system in the development of abdominal inflammation. The features of lymph transport through vessels and nodes, the state of formation and biochemical composition of the lymph, the state of innervation of lymph vessels and nodes, and the state of the cellular composition of lymph nodes in the experimental modeling of inflammation in the abdominal cavities of internal organs reveal new insights regarding the mechanisms of this disease. Since, in the literature, only isolated studies regarding the lymphatic system in violation of the abdominal cavity exist, it is clear that the roles and functional states of lymphatic vessels and nodes in inflammation in the abdominal cavity have not yet been studied in a complex and multi-faceted way. This paper provides data regarding the ratios of the functional structures of lymph nodes after inflammation in the abdominal organs. Lymph systems, including lymph nodes, function as filters of tissues and tissue fluids and are places of origin and lymphocyte production for normal physiological functions. They display specific morphological and functional responses in reaction to endogenous and exogenous substances. The morphological pattern of the mesenteric lymph node in experimental rat groups reflects a decrease in its immune function due to the processes of inflammation in the abdominal cavity. These processes work together with the associated organs and their involvement in the abdominal lymph nodes, in which there are discharges of the structure of the paracortical zone under conditions of reduced lymphogenic processes, according to the decrease in the size of the paracortex and the ratios of lymphoid nodes with and without germinal centers. Histological and morphometric analyses show changes in the mesenteric lymph node. These analyses are characterized by changes in the cortical and medullary substances, while the proportion of the cortical structure decreases. We also noted an increase in the number of macrophages in the lymphoid nodes and cerebral sinus, as well as a decrease in the number of mature plasmocytes, the paracortex, and the pulp strands. These changes indicate immunosuppressive effects on the lymph node. Under the conditions of inflammation, the formation of a mixed immune response occurs. [ABSTRACT FROM AUTHOR]

The spectrum, intensity, and overlap of symptoms between functional gastrointestinal disorders (FGIDs) and other gastrointestinal disorders characterize patients with FGIDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis of FGID and the applicability of a given treatment is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found to cause the continuous existence of a low level of inflammation, which is thought to be a basic pathophysiological process. The idea of the gut–brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and the intestinal functions, including the involvement of gut bacteria. In this review paper, we intend to promote the hypothesis that FGIDs should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic, and microbiome pathways. This hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, that is omnipresent in chronic health conditions. A better understanding of inflammation's role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs may reduce patient heterogeneity and help clarify the pathophysiology of this disease to allow for better treatment. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level of cartilaginous structures and tissues rich in proteoglycans. The pathogenesis of the disease is complex and still incompletely elucidated. The data support the important role of a particular genetic predisposition, with HLA-DR4 being considered an allele that confers a major risk of disease occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers in the development of clinical manifestations, causing the degradation of proteins and the release of cryptic cartilage antigens. Both humoral and cellular immunity play essential roles in the occurrence and perpetuation of autoimmunity and inflammation. Autoantibodies anti-type II, IX and XI collagens, anti-matrilin-1 and anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted in increased titers, being correlated with disease activity and considered prognostic factors. Innate immunity cells, neutrophils, monocytes, macrophages, natural killer lymphocytes and eosinophils have been found in the perichondrium and cartilage, together with activated antigen-presenting cells, C3 deposits and immunoglobulins. Also, T cells play a decisive role in the pathogenesis of the disease, with relapsing polychondritis being considered a TH1-mediated condition. Thus, increased secretions of interferon γ, interleukin (IL)-12 and IL-2 have been highlighted. The "inflammatory storm" formed by a complex network of pro-inflammatory cytokines and chemokines actively modulates the recruitment and infiltration of various cells, with cartilage being a source of antigens. Along with RP, VEXAS syndrome, another systemic autoimmune disease with genetic determinism, has an etiopathogenesis that is still incompletely known, and it involves the activation of the innate immune system through different pathways and the appearance of the cytokine storm. The clinical manifestations of VEXAS syndrome include an inflammatory phenotype often similar to that of RP, which raises diagnostic problems. The management of RP and VEXAS syndrome includes common immunosuppressive therapies whose main goal is to control systemic inflammatory manifestations. The objective of this paper is to detail the main etiopathogenetic mechanisms of a rare disease, summarizing the latest data and presenting the distinct features of these mechanisms. [ABSTRACT FROM AUTHOR]

The members of the Flaviviridae family are becoming an emerging threat for public health, causing an increasing number of infections each year and requiring effective treatment. The consequences of these infections can be severe and include liver inflammation with subsequent carcinogenesis, endothelial damage with hemorrhage, neuroinflammation, and, in some cases, death. The mechanisms of Flaviviridae pathogenesis are being actively investigated, but there are still many gaps in their understanding. Extracellular vesicles may play important roles in these mechanisms, and, therefore, this topic deserves detailed research. Recent data have revealed the involvement of extracellular vesicles in steps of Flaviviridae pathogenesis such as transmission, immune evasion, and inflammation, which is critical for disease establishment. This review covers recent papers on the roles of extracellular vesicles in the pathogenesis of Flaviviridae and includes examples of clinical applications of the accumulated data. [ABSTRACT FROM AUTHOR]

The essential role of nicotinamide adenine dinucleotide+ (NAD+) in redox reactions during oxidative respiration is well known, yet the coenzyme and regulator functions of NAD+ in diverse and important processes are still being discovered. Maintaining NAD+ levels through diet is essential for health. In fact, the United States requires supplementation of the NAD+ precursor niacin into the food chain for these reasons. A large body of research also indicates that elevating NAD+ levels is beneficial for numerous conditions, including cancer, cardiovascular health, inflammatory response, and longevity. Consequently, strategies have been created to elevate NAD+ levels through dietary supplementation with NAD+ precursor compounds. This paper explores current research regarding these therapeutic compounds. It then focuses on the NAD+ regulation of IL-13 signaling, which is a research area garnering little attention. IL-13 is a critical regulator of allergic response and is associated with Parkinson's disease and cancer. Evidence supporting the notion that increasing NAD+ levels might reduce IL-13 signal-induced inflammatory response is presented. The assessment is concluded with an examination of reports involving popular precursor compounds that boost NAD+ and their associations with IL-13 signaling in the context of offering a means for safely and effectively reducing inflammatory response by IL-13. [ABSTRACT FROM AUTHOR]

Cistus spp. have been traditionally used for inflammatory and infectious disorders, including gastrointestinal ailments, in the Mediterranean area. Among them, Cistus × incanus L. is one of the most frequently cited species in the literature for a variety of biological activities which include inflammatory diseases. Cistus spp. aerial parts are rich in polyphenols such as condensed and hydrolysable tannins, procyanidins, and flavonoids, which show gastroprotective activities. The purpose of the present study is to investigate the biological activities of a hydroalcoholic extract from Cistus × incanus L. aerial parts in gastric epithelial cells (GES-1) infected with H. pylori. The extracts inhibited IL-8 and NF-κB induced by H. pylori and showed antibacterial activity after simulated digestion. Since our previous paper reported interesting results on the ability of Castanea sativa Mill. leaf extract to decrease inflammatory conditions in H. pylori-infected gastric cells, the combination of Castanea sativa and Cistus × incanus extracts was also investigated, showing strong anti-inflammatory activity and inhibition of bacterial adhesion. This association of botanicals is proposed herein as a novel food supplement capable of counteracting gastric inflammatory conditions. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment. [ABSTRACT FROM AUTHOR]

The adipose tissue has long been thought to represent a passive source of triglycerides and fatty acids. However, extensive data have demonstrated that the adipose tissue is also a major endocrine organ that directly or indirectly affects the physiological functions of almost all cell types. Obesity is recognized as a risk factor for multiple systemic conditions, including metabolic syndrome, type 2 diabetes mellitus, sleep apnea, cardiovascular disorders, and many others. Obesity-related changes in the adipose tissue induce functional and structural changes in cardiac myocytes, promoting a wide range of cardiovascular disorders, including atrial fibrillation (AF). Due to the wealth of epidemiologic data linking AF to obesity, the mechanisms underlying AF occurrence in obese patients are an area of rich ongoing investigation. However, progress has been somewhat slowed by the complex phenotypes of both obesity and AF. The triad inflammation, oxidative stress, and mitochondrial dysfunction are critical for AF pathogenesis in the setting of obesity via multiple structural and functional proarrhythmic changes at the level of the atria. The aim of this paper is to provide a comprehensive view of the close relationship between obesity-induced oxidative stress, inflammation, and mitochondrial dysfunction and the pathogenesis of AF. The clinical implications of these mechanistic insights are also discussed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex chronic disease of the brain characterized by several neurodegenerative mechanisms and is responsible for most dementia cases in the elderly. Declining immunity during ageing is often associated with peripheral chronic inflammation, and chronic neuroinflammation is a constant component of AD brain pathology. In the Special Issue published in 2021 eight papers were collected regarding different aspects of neurodegeneration associated with AD. Five papers presented and discussed infectious agents involved in brain AD pathology and three discussed data regarding receptors regulation and possible treatment of the disease. Below I will discuss and further elaborate on topics related to infections, inflammation, and neurodegenerative pathways in AD and brain senescence. The topic presented here may contribute to early intervention protocols for preventing or slowing the progression of cognitive deterioration in the elderly. [ABSTRACT FROM AUTHOR]

Bacteria inhabiting the digestive tract are responsible for our health. The microbiome is essential for the development of the immune system and homeostasis of the body. Maintaining homeostasis is very important, but also extremely complicated. The gut microbiome is related to the skin microbiome. It can therefore be assumed that changes in the microbes inhabiting the skin are greatly influenced by the bacteria living in the intestines. Changes in the composition and function of microbes (dysbiosis in the skin and intestines) have recently been linked to changes in the immune response and the development of skin diseases, including atopic dermatitis (AD). This review was compiled by collaborating Dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of the current literature was performed using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis. The inclusion criterion was that the paper was published in a peer-reviewed journal in the last 10 years (2012–2022). No limitations on the language of the publication or the type of study were made. It has been shown that any rapid changes in the composition of the microflora may be associated with the appearance of clinical signs and symptoms of the disease. Various studies have proven that the microbiome of many systems (including the intestines) may have a significant impact on the development of the inflammatory process within the skin in the course of AD. It has been shown that an early interaction between the microbiome and immune system may result in a noticeable delay in the onset of atopic diseases. It seems to be of high importance for physicians to understand the role of the microbiome in AD, not only from the pathophysiological standpoint but also in terms of the complex treatment that is required. Perhaps young children diagnosed with AD present specific characteristics of the intestinal microflora. This might be related to the early introduction of antibiotics and dietary manipulations in breastfeeding mothers in the early childhood of AD patients. It is most likely related to the abuse of antibiotics from the first days of life. [ABSTRACT FROM AUTHOR]

Persistent host inflammatory and immune responses to biofilm play a critical role in the mechanisms that govern soft and hard tissue destruction in periodontal disease. Among the less explored facets of these mechanisms are chemokines, including CCL5 (C-C motif chemokine ligand 5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. Despite its importance, there is currently no comprehensive review of the role of CCL5 in periodontitis in the literature. Therefore, this paper aims to fill this gap by summarizing the existing knowledge on the involvement of CCL5 in the onset and progression of periodontitis. In addition, we aim to stimulate interest in this relatively overlooked factor among periodontitis researchers, potentially accelerating the development of drugs targeting CCL5 or its receptors. The review examines the association of CCL5 with periodontitis risk factors, including aging, cigarette smoking, diabetes, and obesity. It discusses the involvement of CCL5 in pathological processes during periodontitis, such as connective tissue and bone destruction. The data show that CCL5 expression is observed in affected gums and gingival crevicular fluid of periodontitis patients, with bacterial activity contributing significantly to this increase, but the reviewed studies of the association between CCL5 expression and periodontal disease have yielded inconclusive results. Although CCL5 has been implicated in the pathomechanism of periodontitis, a comprehensive understanding of its molecular mechanisms and significance remains elusive, hindering the development of drugs targeting this chemokine or its receptors. [ABSTRACT FROM AUTHOR]

Simple Summary: Even if tongue abscesses are rare, they have very heterogeneous clinical, laboratory and radiological findings. In some cases, their presentation can be particularly nuanced, and they can easily be mistaken for a submucosal malignancy, leading to a dangerous delay in diagnosis. The present paper presents a review of the literature on the possible manifestations (including symptoms, clinical and laboratory findings, imaging) and the management of tongue abscesses in relation to the differential diagnosis of oral tumors. Tongue abscesses are rare conditions that usually follow mucosal disruption due to mechanical trauma or foreign body impaction. They typically manifest abruptly as a rapidly growing, hard mass or swelling in the context of tongue muscles; the patient frequently complains of pain, difficulties in swallowing or speaking, and fever. Nonetheless, the features of its presentation, together with accurate clinical evaluation, blood tests, and appropriate imaging tests, are usually sufficient to easily discern a tongue abscess from a malignancy. However, in rare cases, they may occur with slowly progressing and subtle symptoms, nuanced objective and laboratory findings, and inconclusive radiological evidence, leading to difficult differential diagnosis with submucosal malignancy. Herein, we review the literature, available on Pubmed, Embase, and Scopus, on publications reporting tongue abscesses, with atypical presentation suggesting an oral tumor. Our review confirms that tongue abscesses may manifest as a slowly growing and moderately painful swelling without purulent discharge and minimal mucosal inflammation; in this case, they may constitute an actual diagnostic challenge with potentially severe impact on correct management. Atypical tongue abscesses must therefore be considered in the differential diagnosis of tongue malignancy with submucosal extension, even when other diagnostic elements suggest a neoplasia; in this case, a deep biopsy under general anesthesia is essential for differential diagnosis, and simultaneous drainage of the necrotic and abscessual material may resolve the condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a major burden of disease worldwide, with cancer cachexia being a poor prognosis factor which leads to a decreased quality of life and overall survival. There is an increased need for further studies regarding this complex phenomenon of metabolic imbalances, weight loss, inflammatory changes, and other important pathophysiological components that have a drastic impact on the prognosis of cancer patients. The main goal of this paper is to emphasize the importance of the early detection of cancer patients affected by cachexia and to provide a scientific update regarding the main pathophysiological mechanism involved in cancer cachexia pathogenesis and the complex clinical impact that this pathology has. We aim to raise awareness about the importance of identifying potential biomarkers for the early diagnosis of cancer cachexia, as a key factor in improving patients' management and approach. Cancer remains a major health problem and is associated with cachexia in up to 80% of cases, leading to decreased survival and quality of life. Cachexia involves complex metabolic disturbances in both protein and energy balance, muscle wasting phenomena, weight loss, systemic inflammation, overall decreased performance status, and tolerability to treatment. The clinical impact of cancer cachexia is very complex, with early detection of cachectic patients and identification of predictive biomarkers being two key factors for improving survival. Thus, a better understanding of the complexity of cancer cachexia phenomena and its main pathophysiological mechanism is much needed. Our review highlights the most important information about cancer cachexia, aiming to disseminate updated research findings about this highly deadly condition. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition. [ABSTRACT FROM AUTHOR]

Bronchial asthma is characterized by variable airflow obstruction, airway inflammation, and bronchial hyperresponsiveness (BHR) to non-specific stimuli. The role of underlying airway inflammation and of related long-lasting BHR has been suboptimally investigated in teenagers with mild-to-moderate asthma, as has the corresponding economic impact over time. The aim of the present study was to calculate the cost of mild-to-moderate atopic asthma in teenagers arising from their degree of persisting BHR over a twelve-month period. Methods: Patients aged 12–18 years with mild-to-moderate symptoms treated with fluticasone fumarate/vilanterol 92/22 mcg daily were retrospectively followed for 12 months. Usual spirometric parameters, BHR to methacholine (MCh), and resource consumption (visits, hospitalizations, systemic steroids and/or antibiotics courses, school days off) were assessed at recruitment (the index date) and after 6 and 12 months. Adherence to treatment was also calculated. The cost of asthma was calculated based on Italian tariffs and published papers. The trend over time in BHR and the association between response to MCh and total cost were investigated by using regression models adjusted for repeated measures. Results: 106 teenagers (53 males, age 15.9 ± 1.6 years) were investigated. The annual cost of asthma proved significantly related to the BHR trend: every increment of a factor 10 in the response to MCh was associated with a saving of EUR 184.90 (95% CI −305.89 to −63.90). BHR was progressively optimized after 6 and 12 months in relation to the patients' compliance to treatment (≥70% of prescribed inhalation doses). Conclusions: the usual spirometric parameters are largely insufficient to reflect the effects of underlying persistent inflammation in milder forms of asthma in teenagers. In terms of clinical governance, the periodic assessment of non-specific BHR is the appropriate procedure from this point of view. Non-specific BHR proves a reliable procedure for predicting and monitoring the economic impact of mild-to-moderate asthma in teenagers over time. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, essential oil fractions are emerging as functional compounds of interest for the food and perfume industries. The aim of this study is to evaluate the ability of citral-enriched fractions obtained from lemon essential oil (Cfr-LEO) to counteract, in healthy human hepatocytes, the activity of lipopolysaccharide (LPS), a trigger of inflammation, oxidative stress, and epithelial–mesenchymal transition. In our paper, we report that the pretreatment of hepatocytes with Cfr-LEO counteracts the effects induced by LPS. The data obtained lay the basis for the development of commercial products such as food and drink aimed at preventing or alleviating chronic conditions associated with liver dysfunction. Lemon essential oil (LEO) is known for its aromatic and healthy properties; however, less consideration is given to the biological properties of the fractions obtained from LEO. This study aims to evaluate the ability of a citral-enriched fraction obtained from LEO (Cfr-LEO) to counteract lipopolysaccharide (LPS)-mediated inflammation, oxidative stress, and epithelial–mesenchymal transition (EMT) in healthy human hepatocytes. Human immortalized hepatocytes (THLE-2 cell line) were pretreated with Cfr-LEO and subsequently exposed to LPS at various time points. We report that the pretreatment with Cfr-LEO counteracts LPS-mediated effects by inhibiting inflammation, oxidative stress, and epithelial–mesenchymal transition in THLE-2. In particular, we found that pretreatment with Cfr-LEO reduced NF-κB activation and the subsequent proinflammatory cytokines release, ROS production, and NRF2 and p53 expression. Furthermore, the pretreatment with Cfr-LEO showed its beneficial effect in counteracting LPS-induced EMT. Taken together, these results support Cfr-LEO application in the nutraceutical research field not only for its organoleptic properties, conferred by citral enrichment, but also for its biological activity. Our study could lay the basis for the development of foods/drinks enriched with Cfr-LEO, aimed at preventing or alleviating chronic conditions associated with liver dysfunction. [ABSTRACT FROM AUTHOR]