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Purpose: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [18F]FDG-PET/CT in FUO and IUO based on current evidence. Methods: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with "patients with FUO/IUO" as population, "[18F]FDG-PET/CT" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness. Results: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations. Conclusion: FUO and IUO remains a clinical challenge and [18F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50–60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients. [ABSTRACT FROM AUTHOR]

The paper presents an approach for overcoming modeling problems of typical life science applications with partly unknown mechanisms and lacking quantitative data: A model family of reaction–diffusion equations is built up on a mesoscopic scale and uses classes of feasible functions for reaction and taxis terms. The classes are found by translating biological knowledge into mathematical conditions and the analysis of the models further constrains the classes. Numerical simulations allow comparing single models out of the model family with available qualitative information on the solutions from observations. The method provides insight into a hierarchical order of the mechanisms. The method is applied to the clinics for liver inflammation such as metabolic dysfunction-associated steatohepatitis or viral hepatitis where reasons for the chronification of disease are still unclear and time- and space-dependent data is unavailable. [ABSTRACT FROM AUTHOR]

Background: Tumor is a new organism formed by abnormal hyperplasia of local tissue cells under the action of various tumorigenic factors. Inflammation plays a decisive role in inducing tumorigenesis, promoting tumor development, invasion and migration. More and more evidence indicate that exosomes are involved in regulating the formation of tumor microenvironment in the process of proinflammatory carcinogenesis, leading to the stimulation of anti-tumor immune response or systemic immunosuppression, and exosomes play a crucial role in the development of tumor. Methods: The articles on tumor-derived exosomes and inflammatory responses from January 2005 to January 2024 were collected through Web of Science (WOS), and the inclusion criteria were “Article”, “Review Article” and “Early Access”. Articles obtained after excluding “Book Chapters”, “Editorial Material”, “Proceeding Paper”, “Meeting Abstract” and “Retracted Publication”. Bibliometrics and visualization analysis were carried out on the obtained articles using CiteSpace6.2.R6 and VOSviewer1.6.20. Results: Total of 703 articles were included. The number of published documents showed a fluctuating growth trend year by year. A total of 61 countries have participated in the research on the effects of exosomes and inflammatory responses on tumors, among which China and the United States have the largest influence in this field. The obtained articles have been published in 60 journals around the world, among which PLOS ONE and NAT REV IMMUNOL are the journals with the most published articles and the highest co-citations respectively. The article from French author THERY C was cited the most (202 times). As a major researcher on the basic function of exosomes, THERY C established the gold standard for extraction, separation and identification of exosomes, and found that exosomes promote tumor metastasis through direct regulation of miRNA. Her research has had a huge impact on the field. Keyword co-occurrence analysis indicate that extracellular vesicles, inflammation, cancer, miRNAs, mesenchymal stem cells, drug delivery, gastric cancer and circulating endothelial microparticles are the research hotspot at present stage. The main keywords of the cluster analysis show that extracellular vesicles, human papilloma virus, myeloid cells, tumor macro-environment are the current research hotspots and frontier. The research hotspots have developed over time from the time chart of keywords and clustering, especially after 2016, exosomes have established extensive links with drug delivery, cancer treatment, inflammatory response and other fields. Tumor-derived exosomes stimulate receptor cells to secrete pro-inflammatory cytokines and growth factors, enabling immune and inflammatory cells to perceive the intracellular environment of cancer cells even when cancer cells do not express any tumor-specific antigens. For example, in anoxic environment, cancer cells can secrete exosomes containing pro-inflammatory factors to promote the invasion and metastasis of cancer cells. In the complex tumor microenvironment, both tumor cells and various stromal cells will secrete specific exosomes, and promote the development of tumors through various ways, so that tumor cells have drug resistance, and bring adverse effects on the clinical treatment of tumor patients. MicroRNAs and long noncoding RNA as hot keywords play important roles in regulating and mediating tumor development, and their specificity makes them important biomarkers for cancer prediction and diagnosis. Highlighting word analysis shows that microRNAs secreted by leukemia patients can effectively promote the proliferation of malignant cells and the development of cardiovascular diseases. At the same time, exosomes can induce the secretion of some microRNAs in patients, leading to cardiac repair and regeneration. Therefore, the detection and screening of microRNAs plays a crucial role in predicting the incidence of cardiovascular diseases in patients. Conclusion: Exosomes have attracted increasing attention due to their significant heterogeneity and ability to regulate the tumor immune microenvironment. However, tumor cell-derived exosomes accelerate tumor progression by enhancing immunosuppression and inflammation, increasing oxidative stress, and promoting angiogenesis, which may lead to poor prognosis. [ABSTRACT FROM AUTHOR]

Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain. The neuroinflammatory processes may exhibit varying characteristics based on the specific type of anticancer treatment delivered. Neuroinflammatory characteristics have been observed in the spinal cord, where microglia and astrocytes have a significant impact on the development of chemotherapy-induced peripheral neuropathy. The patient's quality of life might be affected by sensory deprivation, loss of consciousness, paralysis, and severe disability. High cancer rates and ineffective treatments are associated with this disease. Recently, histone deacetylases have become a novel treatment target for chemotherapy-induced neuropathic pain. Chemotherapy-induced neuropathic pain may be treated with histone deacetylase inhibitors. Histone deacetylase inhibitors may be a promising therapeutic treatment for chemotherapy-induced neuropathic pain. Common chemotherapeutic drugs, mechanisms, therapeutic treatments for neuropathic pain, and histone deacetylase and its inhibitors in chemotherapy-induced neuropathic pain are covered in this paper. We propose that histone deacetylase inhibitors may treat several aspects of chemotherapy-induced neuropathic pain, and identifying these inhibitors as potentially unique treatments is crucial to the development of various chemotherapeutic combination treatments. [ABSTRACT FROM AUTHOR]

Background: The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. Objective: In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved in maternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. Conclusion: The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) in children is a rare but devastating condition. Once a critical amount of nephron mass has been lost, progression of CKD is irreversible and results in end-stage renal disease (ESRD) and need of renal replacement therapy. The time course of childhood CKD is highly variable. While in children suffering from congenital anomalies of the kidneys and the urinary tract, progression of CKD in general is slow, in children with acquired glomerulopathies, disease progression can be accelerated resulting in ESRD within months. However, irrespective of the underlying kidney disease, hypertension and proteinuria are independent risk factors for progression. Thus, in order to prevent progression, the primary objective of treatment should always aim for efficient control of blood pressure and reduction of urinary protein excretion. Blockade of the renin-angiotensin-aldosterone system preserves kidney function not only by lowering blood pressure, but also by reducing proteinuria and exerting additional anti-proteinuric, anti-fibrotic, and anti-inflammatory effects. Besides, intensified blood pressure control, aiming for a target blood pressure below the 50th percentile, may exert additive renoprotective effects. Additionally, other modifiable risk factors, such as anemia, metabolic acidosis, dyslipidemia, and altered bone-mineral homeostasis may also contribute to CKD progression. In conclusion, beyond strict blood pressure control and reduction of urinary protein excretion, identification and treatment of both, renal disease-related and conventional risk factors are mandatory in children with CKD in order to prevent deterioration of kidney function. [ABSTRACT FROM AUTHOR]

The highly diverse microbial ecosystem of the human body colonizes the gastrointestinal tract has a profound impact on the host’s immune, metabolic, endocrine, and other physiological processes, which are all interconnected. Specifically, gut microbiota has been found to play a crucial role in facilitating the adaptation and initiation of immune regulatory response through the gastrointestinal tract affecting the other distal mucosal sites such as lungs. A tightly regulated lung-gut axis during respiratory ailments may influence the various molecular patterns that instructs priming the disease severity to dysregulate the normal function. This review provides a comprehensive summary of current research on gut microbiota dysbiosis in respiratory diseases including asthma, pneumonia, bronchopneumonia, COPD during infections and cancer. A complex-interaction among gut microbiome, associated metabolites, cytokines, and chemokines regulates the protective immune response activating the mucosal humoral and cellular response. This potential mechanism bridges the regulation patterns through the gut-lung axis. This paper aims to advance the understanding of the crosstalk of gut-lung microbiome during infection, could lead to strategize to modulate the gut microbiome as a treatment plan to improve bad prognosis in various respiratory diseases. [ABSTRACT FROM AUTHOR]

Introduction: An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog®, Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph®) assessments. Methods: This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score. Results: Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15 days (6.4 ± 3.6 vs 5.4 ± 3.7 s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45 days (6.8 ± 2.6 vs 5.6 ± 2.3 s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage. Conclusion: These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3–6 months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a life-threatening clinical syndrome with high morbidity and mortality. The main pathological features of ALI are increased alveolar-capillary membrane permeability, edema, uncontrolled migration of neutrophils to the lungs, and diffuse alveolar damage, resulting in acute hypoxemic respiratory failure. We performed a systematic review and meta-analysis to elucidate the antioxidant activities of flavanols in a rat model of acute lung injury (ALI). PubMed, EMBASE, Scopus, ProQuest, Web of Science, and Google Scholar databases were searched to obtain the relevant papers. Nine studies with 343 rat models of ALI were included in this study. We investigated oxidative stress with the corresponding 95% CI. Estimating the correlation and 95% CIs for the inflammatory agents and oxidative stress in the intervention group, compared with that in the control group (ALI), respectively (correlation: 0.635; 95% CI, 0.560–0.699, P value = 0.000, Z value= 12.648) and (correlation: 0.317; 95% CI, 0.189–0.434, P value = 0.00, Z value= 4.7). In conclusion, investigating the effects of different flavanols on oxidative stress in lung injury may provide a useful therapeutic strategy in ALI mouse models. However, the final conclusion on treatment efficacy should be sufficient for prospective controlled randomized trials. [ABSTRACT FROM AUTHOR]

Objective: To identify adhesive renal venous tumor thrombus (RVTT) of renal cell carcinoma (RCC) by contrast-enhancement CT (CECT). Materials and methods: Our retrospective study included 53 patients who underwent preoperative CECT and pathologically confirmed RCC combined with RVTT. They were divided into two groups based on the intra-operative findings of RVTT adhesion to the venous wall, with 26 cases in the adhesive RVTT group (ARVTT) and 27 cases in the non-adhesive group (NRVTT). The location, maximum diameter (MD) and CT values of tumors, the maximum length (ML) and width (MW) of RVTT, and length of inferior vena cava tumor thrombus were compared between the two groups. The presence of renal venous wall involvement, renal venous wall inflammation, and enlarged retroperitoneal lymph node was compared between the two groups. A receiver operating characteristic curve was used to analyze the diagnostic performance. Results: The MD of RCC and the ML and MW of the RVTT were all larger in the ARVTT group than in the NRVTT group (p = 0.042, p < 0.001, and p = 0.002). The proportion of renal vein wall involvement and renal vein wall inflammation were higher in the ARVTT group than in NRVTT groups (both p < 0.001). The multivariable model including ML and vascular wall inflammation to predict ARVTT could achieve the best diagnostic performance with the area under the curve, sensitivity, specificity, and accuracy of 0.91, 88.5%, 96.3%, and 92.5%, respectively. Conclusion: The multivariable model acquired by CECT images could be used to predict RVTT adhesion. Clinical relevance statement: For RCC patients with tumor thrombus, contrast-enhanced CT could noninvasively predict the adhesion of tumor thrombus, thus predicting the difficulty of surgery and contributing to the selection of an appropriate treatment plan. Key Points: • The length and width of the tumor thrombus could be used to predict its adhesion to the vessel wall. • Adhesion of the tumor thrombus can be reflected by inflammation of the renal vein wall. • The multivariable model from CECT can well predict whether the tumor thrombus adhered to the vein wall. [ABSTRACT FROM AUTHOR]

To date, few papers investigated the predictive factors of sustained 24-month remission and of flare in patients with polymyalgia rheumatica (PMR). We retrospectively evaluated clinical charts from PMR patients. Patients were evaluated at baseline, at 1 month, 3 months and subsequently at 6, 12 and 24 months. We analyzed the differences between patients who achieved remission within 6 months of diagnosis, those who achieved remission at 24 months, and patients who did not. Among 137 patients, 57 (41.6%) achieved remission at 6 months and complete remission at 24 months was achieved by 104 patients (75.9%). The erythrocyte sedimentation rate at baseline was higher in patients who did not achieve remission than in patients who achieved it (p = 0.012). Female patients were less likely to achieve complete remission (45/68, 66.2% vs. 59/69, 85.5%, p = 0.01) compared to males. Fifty-four patients (39.4%) experienced at least one flare. Patients who did not achieve sustained complete remission suffered a flare more often (22/39 vs. 32/98, p = 0.01) and earlier than patients who did (10.33 ± 7.89 months vs. 13.64 ± 6.97 months, p = 0.011). Multivariate analysis confirmed that female sex (RR = 3.2, 95% CI 1.3–7.9) and higher baseline prednisone dosage (RR = 1.1, 95% CI 1.007–1.109) were negative independent predictors of complete remission at 24 months. A significant percentage of patients with PMR requires prolonged steroid treatment and may experience flares at 24 months of follow-up. Female sex and higher baseline prednisone dosage are negative independent predictors of complete remission at 24 months. [ABSTRACT FROM AUTHOR]

As a chronic inflammatory disease, periodontitis involves many biological processes including autophagy. At the same time, casein kinase 2 interacting protein-1 (CKIP-1) was reported to play a role in regulation of inflammation. But whether CKIP-1 and autophagy interact in periodontitis remains unclear. In this paper, our research team verified the levels of CKIP-1 expression and autophagy increase in the periodontal tissues of a ligature-induced periodontitis mouse model. And this result was also confirmed in Porphyromonas gingivalis (Pg)-induced human gingival fibroblasts (HGF) and human periodontal ligament cells (PDLC). We also showed the autophagy level in periodontal tissues is higher in Ckip-1 knockout (KO) mice than wild type (WT). At the same time, CKIP-1 knockdown lentivirus was used in PDLC and HGF, and it was found that silencing CKIP-1 significantly activated autophagy. Unfortunately, the regulatory role of autophagy in periodontitis is still unclear. Then, the autophagy agonist Rapamycin and inhibitor 3-MA were used in a periodontitis mouse model to investigate periodontal tissue destruction. We found the inflammation in periodontal tissue was reduced when autophagy activated. All these conclusions have been verified both in vivo and in vitro experiments. Finally, our research proved that silencing CKIP-1 reduces the expression of inflammatory cytokines in Pg-induced PDLC and HGF by regulating autophagy. Overall, a new role for CKIP-1 in regulating periodontal tissue inflammation was demonstrated in our study, and it is possible to treat periodontitis by targeting the CKIP-1 gene. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is one of the most common nutritional problems in patients with obesity and after bariatric surgery. While it can be reduced with diet and oral supplementation, a subset of patients is refractory to these measures. Several factors have been implicated including high hepcidin levels reducing the release of absorbed iron into the circulation. We found 6 papers studying hepcidin levels before and after bariatric surgery. Patients with obesity have higher hepcidin and other inflammatory markers. Five out of six studies reported significant falls in hepcidin levels after bariatric surgery. This was accompanied by an improvement in the RBC morphology indices in restrictive surgeries. However, the fall in hepcidin is not uniform and may be a contributing factor for refractory IDA. [ABSTRACT FROM AUTHOR]

We present a Bayesian partial membership model that estimates the associations between an outcome, a small number of latent variables, and multiple observed exposures where the number of latent variables is specified a priori. We assign one observed exposure as the sentinel marker for each latent variable. The model allows non-sentinel exposures to have complete membership in one latent group, or partial membership across two or more latent groups. MCMC sampling is used to determine latent group partial memberships for the non-sentinel exposures, and estimate all model parameters. We compare the performance of our model to competing approaches in a simulation study and apply our model to inflammatory marker data measured in a large mother-child cohort of the Seychelles Child Development Study (SCDS). In simulations, our model estimated model parameters with little bias, adequate coverage, and tighter credible intervals compared to competing approaches. Under our partial membership model with two latent groups, SCDS inflammatory marker classifications generally aligned with the scientific literature. Incorporating additional SCDS inflammatory markers and more latent groups produced similar groupings of markers that also aligned with the literature. Associations between covariates and birth weight were similar across latent variable models and were consistent with earlier work in this SCDS cohort. Supplementary materials accompanying this paper appear online. [ABSTRACT FROM AUTHOR]

Perioperative neurocognitive disorder (PND) is a common disorder following anesthesia and surgery, especially in the elderly. The complex cellular and molecular processes are involved in PND, but the underlying pathogenesis of which remains inconclusive due to conflicting data. A growing body of evidence has been shown that perioperative systemic inflammation plays important roles in the development of PND. We reviewed the relevant literature retrieved by a search in the PubMed database (on July 20, 2023). The search terms used were "delirium", "post operative cognitive dysfunction", "perioperative neurocognitive disorder", "inflammation" and "systemic", alone and in combination. All articles identified were English-language, full-text papers. The ones cited in the review are those that make a substantial contribution to the knowledge about systemic inflammation and PNDs. The aim of this review is to bring together the latest evidence for the understanding of how perioperative systemic inflammation mediates neuroinflammation and brain injury, how the inflammation is regulated and how we can translate these findings into prevention and/or treatment for PND. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate and pinpoint the status, hot areas, and frontiers of immune activation during HIV infection utilizing CiteSpace. From 1990 to 2022, we searched for studies on immune activation during HIV infection in the Web of Science Core Collection. CiteSpace was used to visually analyze the publications to identify the research status and pertinent research hotspots and frontiers in terms of the countries, institutions, authors, references, journals, and keywords. The Web of Science Core Collection yielded 5321 articles on immune activation during HIV infection. With 2854 and 364 articles, the United States and the University of California, San Francisco were the leading nation and institution in this domain. Steven G. Deeks has published 95 papers and is the most published author. The top cited articles on microbial translocation as a significant factor during HIV infection were published by Brenchley et al. Research on molecular/biology/genetics is often referenced in publications in the journals of molecular/biology/immunology. Inflammation, risk, mortality, cardiovascular disease, persistence, and biomarkers will be high-frequency words that are hot topics of research. According to the results, there was a strong collaboration between countries and organizations but little collaboration among authors. Molecular biology, immunology, and medicine are the main study subjects. The current hot topics in research are inflammation, risk, mortality, cardiovascular disease, persistence, and biomarkers. Future studies should concentrate on reducing the pathological changes caused by inflammation and altering the mechanisms of immune activation to reduce the size of the viral reservoir. [ABSTRACT FROM AUTHOR]

For a long time Nrf2 transcription factor has been attracting attention of researchers investigating phenomenon of aging. Numerous studies have investigated effects of Nrf2 on aging and cell senescence. Nrf2 is often considered as a key player in aging processes, however this needs to be proven. It should be noted that most studies were carried out on invertebrate model organisms, such as nematodes and fruit flies, but not on mammals. This paper briefly presents main mechanisms of mammalian aging and role of inflammation and oxidative stress in this process. The mechanisms of Nrf2 activity regulation, its involvement in aging and development of the senescence-associated secretory phenotype (SASP) are also discussed. Main part of this review is devoted to critical analysis of available experimental data on the role of Nrf2 in mammalian aging. [ABSTRACT FROM AUTHOR]

Objectives: Scutellaria baicalensis (SB) has been traditionally used to combat a variety of conditions ranging from ischemic heart disease to cancer. The protective effects of SB are due to the action of two main flavonoids baicalin (BA) and baicalein (BE). This paper aimed to provide a narrative review of the protective and antidotal effects of SB and its main constituents against natural toxicities and physical hazards. Evidence acquisition: Scientific databases Medline, Scopus, and Web of Science were thoroughly searched, based on different keywords for in vivo, in vitro and clinical studies which reported protective or therapeutic effects of SB or its constituents in natural and physical toxicities. Results: Numerous studies have reported that treatment with BE, BA, or total SB extract prevents or counteracts the detrimental toxic effects of various natural compounds and physical hazards. The toxic agents include mycotoxins, lipopolysaccharide, multiple plants and animal-derived substances as well as physical factors which negatively affected vital organs such as CNS, liver, kidneys, lung and heart. Increasing the expression of radical scavenging enzymes and glutathione content as well as inhibition of pro-inflammatory cytokines and pro-apoptotic mediators were important mechanisms of action. Conclusion: Different studies on the Chinese skullcap have exhibited that its total root extract, BA or BE can act as potential antidotes or protective agents against the damage induced by natural toxins and physical factors by alleviating oxidative stress and inflammation. However, the scarcity of high-quality clinical evidence means that further clinical studies are required to reach a more definitive conclusion. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) was a serious nerve injury, which involves complex genetic changes. This paper was intended to investigate the function and mechanism of differentially expressed genes in SCI. The three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database were used to identify differentially expressed genes (DEGs). We identified the common DEGs in the three datasets GSE92657, GSE93561 and GSE189070 of SCI from GEO database. Next, a protein-protein interaction (PPI) network of DEGs was constructed. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in immune response, inflammatory response. The expression level of immune-related genes (Arg1, Ccl12, Ccl2, Ifitm2, Ifitm3, and et al.) at different time points of SCI were analyzed in GSE189070 dataset. Next, differentially expressed miRNAs (DE-miRNAs) were identified in SCI compared with normal based on GSE158194 database. DE-miRNA and targeted immune-related genes were predicted by miRwalk, including miR-487b-5p targeted Ifitm3, miR-3072-5p targeted Ccl3, and et al. What's more, the miR-487b was identified and verified to be down-regulated in Lipopolysaccharide (LPS)-induced BV-2 cell model. Further, the miR-487b inhibited cell inflammation and apoptosis in LPS-induced BV2 cell by targeted Ifitm3. For the first time, our results revealed that miR-487b may play an important regulatory role in SCI by targeted Ifitm3 and provide further evidence for SCI research. [ABSTRACT FROM AUTHOR]

Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.Graphical abstract: Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations. [ABSTRACT FROM AUTHOR]

Introduction: Patients undergoing elective laparoscopic cholecystectomy (ELLC) represent a heterogeneous group making it challenging to stratify risk. The aim of this paper is to identify pre-operative factors associated with adverse peri- and post-operative outcomes in patients undergoing ELLC. This knowledge will help stratify risk, guide surgical decision making and better inform the consent process.Methods: All patients who underwent ELLC between January 2015 and December 2019 were included in the study. Pre-operative data and both peri- and post-operative outcomes were collected retrospectively from multiple databases using a deterministic records-linkage methodology. Patients were divided into groups based on clinical indication (i.e. biliary colic versus cholecystitis) and adverse outcomes were compared. Multivariate regression models were generated for each adverse outcome using pre-operative independent variables.Results: Two-thousand one hundred and sixty-six ELLC were identified. Rates of peri- and post-operative adverse outcomes were significantly higher in the cholecystitis versus biliary colic group and increased with number of admissions of cholecystitis (p < 0.05). Rates of subtotal (29.5%), intra-operative complication (9.8%), post-operative complications (19.6%), prolonged post-operative stay (45.9%) and re-admission (16.4%) were significant in the group of patients with ≥ 2 admissions with cholecystitis.Conclusion: Our data demonstrate that patients with repeated biliary admission (particularly cholecystitis) ultimately face an increased risk of a difficult ELLC with associated complications, prolonged post-operative stay and readmissions. These data provide robust evidence that individualised risk assessment and consent are necessary before ELLC. Strategies to minimise recurrent biliary admissions prior to LC should be implemented. [ABSTRACT FROM AUTHOR]

Background: Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate. Aims: To give new insights into cachexia's pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases. Methods: A systematic review was performed in PubMed using the keywords ("cancer" OR "cardiac" cachexia AND "human" OR "patient" AND "plasma" or "serum"). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators. Results: Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients. Conclusion: The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The unique physicochemical properties of materials at nanoscale have opened a plethora of opportunities for applications in the pharmaceutical and medical field, but also in consumer products from food and cosmetics industries. As a consequence, daily human exposure to nanomaterials through distinct routes is considerable and, therefore, may raise health concerns. Many nanomaterials have been described to accumulate and induce adversity in the liver. Among these, silica and some types of metallic nanoparticles are the most broadly used in consumer products and, therefore, the most studied and reported. The reviewed literature was collected from PubMed.gov during the month of March 2020 using the search words "nanomaterials induced hepatotoxicity", which yielded 181 papers. This present paper reviews the hepatotoxic effects of nanomaterials described in in vitro and in vivo studies, with emphasis on the underlying mechanisms. The induction of oxidative stress and inflammation are the manifestations of toxicity most frequently reported following exposure of cells or animal models to different nanomaterials. Furthermore, the available in vitro models for the evaluation of the hepatotoxic effects of nanomaterials are discussed, highlighting the continuous interest in the development of more advanced and reliable in vitro models for nanotoxicology. [ABSTRACT FROM AUTHOR]

Isoflurane (ISO) has been widely used in clinical anesthesia, and exposure to ISO leads to cognitive dysfunction. Our paper aimed to investigate the effect of miR-128-3p on cognitive impairment, inflammation, and oxidative stress elicited by ISO anesthesia in Sprague–Dawley (SD) rats. The SD rats were treated with ISO to mimic the ISO-injured situation, and the concentration of miR-128-3p was quantified utilizing real-time PCR. The miR-128-3p's impacts in ISO-engendered rat models on the respects of inflammatory condition and oxidative activities were measured by the commercial kits. The Morris water maze test was adopted to measure the neuro-function regarding miR-128-3p. Additionally, the target was tested by the alternation of luciferase activity. The irritation of ISO suppressed miR-128-3p expression in rats, which was enhanced by the injection of miR-128-3p agomir. The adverse roles of ISO on inflammation, oxidative stress, and cognitive disorders were partially abrogated by an increment of miR-128-3p. A miR-128-3p's interconnection with specificity protein 1 (SP1) was pinpointed, and aggrandized mRNA levels of SP1 were found under ISO state. MiR-128 acted as a regulator in ISO damage in the respects of cognition, inflammation, and oxidative stress. The SP1's link of miR-128-3p was showcased. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD), the main risk factor for which is age, is one of the most common neurodegenerative diseases and imposes a substantial burden on affected individuals and the economy. While the aetiology of PD is still largely unclear, substantial evidence indicates that mitochondrial dysfunction, aggregation of α-synuclein (α-syn), oxidative stress, inflammation, and autophagy play major roles in the pathogenesis of PD. Sirtuins are NAD+-dependent protein deacetylases, includeing seven members, i.e., SIRT1-SIRT7. Among these sirtuins, SIRT3, SIRT4 and SIRT5 are located in mitochondria and are called mitochondrial sirtuins. Mitochondrial sirtuins regulate the activity and biological function of mitochondrial proteins through posttranslational modification of substrate proteins. Increasing evidence shows that mitochondrial sirtuins play an important role in degenerative diseases, including PD. Mitochondrial sirtuins exert a beneficial neuroprotective effect in various models of PD. This paper summarizes a large number of studies and discusses the latest research progress on the role of mitochondrial sirtuins in PD, focusing especially on the regulation of the mitochondrial respiratory chain (MRC), oxidative stress, the inflammatory response and autophagy, to provide new insight into the pathogenesis of PD and new targets for the diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), is a heavy metal reported to be associated with oxidative stress and inflammation. In this paper, we investigated the possible protective effects of carvacrol against Cd-induced neurotoxicity in rats. Adult male Sprague Dawley rats were treated orally with Cd (25 mg/kg body weight) and with carvacrol (25 and 50 mg/kg body weight) for 7 days. Carvacrol decreased the levels of malondialdehyde (MDA), glial fibrillary acidic protein (GFAP) and monoamine oxidase (MAO), and significantly increased the levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in brain tissue. Additionally, carvacrol alleviated the in levels of inflammation and apoptosis related proteins involving p38 mitogen-activated protein kinase (p38 MAPK), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), B-cell lymphoma-3 (Bcl-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), prostaglandin E2 (PGE2), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), cysteine aspartate specific protease-3 (caspase-3) and Bcl-2 associated X protein (Bax) in the Cd-induced neurotoxicity. Carvacrol also decreased the mRNA expression of matrix metalloproteinases (MMP9 and MMP13), as well as 8-hydroxy-2′-deoxyguanosine (8 − OHdG) level, a marker of oxidative DNA damage. Collectively, our findings indicated that carvacrol has a beneficial effect in ameliorating the Cd-induced neurotoxicity in the brain of rats. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic, progressive and second most prevalent neurological disorder affecting the motor system. Cardinal motor impairment and α-synucleinopathy are the characteristic features of PD. Recently, it has been identified that the gut-brain axis is substantially regulated by the gut microbiome (GM) through an immunological, neuroendocrine, and neural mechanism. However, disturbance in the gut-microbiome-brain axis in PD might proceed to gastrointestinal manifestations intermittently leading to the motor system and the PD pathogenesis itself. The gut microbial toxins may induce the production of α-synuclein (α-syn) aggregates in the enteric nervous system (ENS), which may proliferate and propagate in a prion-like-manner through the vagus nerve to the central nervous system (CNS); supporting the hypothesis that, GM might play a pivotal role in PD pathogenesis. Overstimulated innate immune system due to intestinal bacterial overgrowth or gut dysbiosis and the enhanced intestinal permeability may persuade systemic inflammation, while the activation of enteric glial cells and enteric neurons may contribute to α-synucleinopathy. Gut microbiota can bear a significant impact on neurological outcomes such as learning, memory and cognition. In this review paper, we summarize how the alterations in gut microbiota and ENS inflammation are associated with PD pathogenesis. The evidence supporting the causative role played by gut-associated dysbiosis and microbial byproducts, in the onset of PD is also discussed. We have highlighted the landmark discoveries in the field of PD particularly focusing on the gut-brain axis. A better comprehension of the interaction between the gut-brain axis, gut microbiota, and PD can usher in novel therapeutic and diagnostic approaches. [ABSTRACT FROM AUTHOR]

Ethyl pyruvate (EP) has potent influence on redox processes, cellular metabolism, and inflammation. It has been intensively studied in numerous animal models of systemic and organ-specific disorders whose pathogenesis involves a strong immune component. Here, basic chemical and biological properties of EP are discussed, with an emphasis on its redox and metabolic activity. Further, its influence on myeloid and T cells is considered, as well as on intracellular signaling beyond its effect on immune cells. Also, the effects of EP on animal models of chronic inflammatory and autoimmune disorders are presented. Finally, a possibility to apply EP as a treatment for such diseases in humans is discussed. Scientific papers cited in this review were identified using the PubMed search engine that relies on the MEDLINE database. The reference list covers the most important findings in the field in the past twenty years. [ABSTRACT FROM AUTHOR]

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper. [ABSTRACT FROM AUTHOR]

Public health is threatened by climate change and extreme temperature events worldwide. Differences in health predispositions, access to cooling infrastructure and occupation raises an issue of heat-related health inequality in those vulnerable and disadvantaged demographic groups. To address these issues, a comprehensive understanding of the effect of elevated body temperatures on human biological systems and overall health is urgently needed. In this paper we look at the inner workings of the human innate immunity under exposure to heat stress induced through exposure to environment and physical exertion. We couple two experimentally validated computational models: the innate immune system and thermal regulation of the human body. We first study the dynamics of critical indicators of innate immunity as a function of human core temperature. Next, we identify environmental and physical activity regimes that lead to core temperature levels that can potentially compromise the performance of the human innate immunity. Finally, to take into account the response of innate immunity to various intensities of physical activities, we utilise the dynamic core temperatures generated by a thermal regulation model. We compare the dynamics of all key players of the innate immunity for a variety of stresses like running a marathon, doing construction work, and leisure walking at speed of 4 km/h, all in the setting of a hot and humid tropical climate such as present in Singapore. We find that exposure to moderate heat stress leading to core temperatures within the mild febrile range (37, 38] ∘ C , nudges the innate immune system into activation and improves the efficiency of its response. Overheating corresponding to core temperatures beyond 38 ∘ C , however, has detrimental effects on the performance of the innate immune system, as it further induces inflammation, which causes a series of reactions that may lead to the non-resolution of the ongoing inflammation. Among the three physical activities considered in our simulated scenarios (marathon, construction work, and walking), marathon induces the highest level of inflammation that challenges the innate immune response with its resolution. Our study advances the current state of research towards understanding the implications of heat exposure for such an essential physiological system as the innate immunity. Although we find that among considered physical activities, a marathon of 2 h and 46 min induces the highest level of inflammation, it must be noted that construction work done on a daily basis under the hot and humid tropical climate, can produce a continuous level of inflammation triggering moieties stretched at a longer timeline beating the negative effects of running a marathon. Our study demonstrates that the performance of the innate immune system can be severely compromised by the exposure to heat stress and physical exertion. This poses significant risks to health especially to those with limited access to cooling infrastructures. This is due in part to having low income, or having to work on outdoor settings, which is the case for construction workers. These risks to public health should be addressed through individual and population-level measures via behavioural adaptation and provision of the cooling infrastructure in outdoor environments. [ABSTRACT FROM AUTHOR]

Considering the central role of inflammation in the pathogenesis of periodontitis, the combination of NSPT with different agents that can modulate the host immune-inflammatory response has been proposed to enhance the outcomes of NSPT. The aim of this paper is to systematically review the literature on the efficacy of systemic host modulators (HMs) as adjuncts to non-surgical periodontal therapy (NSPT) in improving pocket depth (PD) reduction and clinical attachment level (CAL) gain in healthy and systemically compromised patients. RCTs with ≥ 3 months follow-up were independently searched by two reviewers. Meta-analysis was performed when ≥ 3 studies on the same HM were identified. The quality of the evidence was rated according to the GRADE approach to rate the certainty of evidence. 38 articles were included in the qualitative assessment and 27 of them were included in the meta-analysis. There is low/very low evidence that the adjunctive use of sub-antimicrobial dose of doxycicline, melatonin and the combination of omega-3 and low dose aspirin (in type 2 diabetic patients) to NSPT would improve PD and/or CAL. Conflicting evidence is available on the efficacy of probiotics. Future studies controlling for confounding factors, using composite outcomes to define the endpoint of therapy and considering not only the patient- but also as the site-specific effect of systemic HMs are warranted. The dosage, posology and long-term effect of HMs still need to be clarified, also in association to the presence of systemic conditions potentially affecting the response to HMs administration. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammation that can lead to loss of range of joint abnormalities in severe cases. Diosgenin has anti-inflammatory effects. This paper discussed the effect and mechanism of diosgenin on excessive proliferation and inflammatory response of synovial cells in RA. CCK-8 detected the cell viability, TUNEL assay detected the apoptosis of cells and western blot detected the expression of apoptosis-related proteins. Wound healing was used to detect cell migration and western blot detected the expression of migration-related proteins. ELISA kits were used to detect the levels of inflammatory cytokines in cells. Diosgenin can inhibit the proliferation and migration of RA synovial cells. At the same time, diosgenin could reduce the inflammatory response of RA synovial cells, during which the expression of PDE3B was significantly decreased. By overexpressing PDE3B, we found that diosgenin inhibited the proliferation, migration, and inflammatory response of RA synovial cells by downregulating PDE3B. Diosgenin can inhibit excessive proliferation and inflammatory response of synovial fibroblasts by targeting PDE3B. [ABSTRACT FROM AUTHOR]

Most acute nontraumatic periorbital and intraorbital pathologies in pediatric patients have an underlying infectious or inflammatory etiology, and imaging frequently plays a key role in the workup and management of these children. In this paper we review the clinical presentation and imaging findings in children with some of the most common infectious and inflammatory diseases involving the orbit. Basic relevant anatomy and imaging findings on various imaging modalities are also reviewed. [ABSTRACT FROM AUTHOR]

Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients. The R/R ratio, assessed as a combination of the paraoxonase 1 (PON1) gene, PON1 enzymatic activity, and early life time trauma (ELT), predicted the high-density lipoprotein cholesterol – paraoxonase 1 complex (HDL-PON1), reactive oxygen and nitrogen species (RONS), nitro-oxidative stress toxicity (NOSTOX), staging (number of depression and hypomanic episodes and suicidal attempts), and phenome (the Hamilton Depression and Anxiety scores and the Clinical Global Impression; current suicidal ideation; quality of life and disability measurements) scores. Partial Least Squares pathway analysis showed that 44.2% of the variance in the phenome was explained by ELT, RONS/NOSTOX, and staging scores. Cluster analysis conducted on all those feature sets discovered two distinct patient clusters, namely 69.5% of the patients were allocated to a class with high R/R, RONS/NOSTOX, staging, and phenome scores, and 30.5% to a class with increased staging and phenome scores. This classification cut across the bipolar (BP1/BP2) and major depression disorder classification and was more distinctive than the latter classifications. We constructed a nomothetic network model which reunited all features of mood disorders into a mechanistically transdiagnostic model. [ABSTRACT FROM AUTHOR]

Tumor cells, inflammatory cells and chemical factors work together to mediate complex signaling networks, which forms inflammatory tumor microenvironment (TME). The development of breast cancer is closely related to the functional activities of TME. This review introduces the origins of cancer-related chronic inflammation and the main constituents of inflammatory microenvironment. Inflammatory microenvironment plays an important role in breast cancer growth, metastasis, drug resistance and angiogenesis through multifactorial mechanisms. It is suggested that inflammatory microenvironment contributes to providing possible mechanisms of drug action and modes of drug transport for anti-cancer treatment. Nano-drug delivery system (NDDS) becomes a popular topic for optimizing the design of tumor targeting drugs. It is seen that with the development of therapeutic approaches, NDDS can be used to achieve drug-targeted delivery well across the biological barriers and into cells, resulting in superior bioavailability, drug dose reduction as well as off-target side effect elimination. This paper focuses on the review of modulation mechanisms of inflammatory microenvironment and combination with nano-targeted therapeutic strategies, providing a comprehensive basis for further research on breast cancer prevention and control. [ABSTRACT FROM AUTHOR]

Reflectance confocal microscopy (RCM) is a non-invasive imaging tool that reduces the need for invasive histopathology for skin cancer diagnoses by providing high-resolution mosaics showing the architectural patterns of skin, which are used to identify malignancies in-vivo. RCM mosaics are similar to dermatopathology sections, both requiring extensive training to interpret. However, these modalities differ in orientation, as RCM mosaics are horizontal (parallel to the skin surface) while histopathology sections are vertical, and contrast mechanism, RCM with a single (reflectance) mechanism resulting in grayscale images and histopathology with multi-factor color-stained contrast. Image analysis and machine learning methods can potentially provide a diagnostic aid to clinicians to interpret RCM mosaics, eventually helping to ease the adoption and more efficiently utilizing RCM in routine clinical practice. However standard supervised machine learning may require a prohibitive volume of hand-labeled training data. In this paper, we present a weakly supervised machine learning model to perform semantic segmentation of architectural patterns encountered in RCM mosaics. Unlike more widely used fully supervised segmentation models that require pixel-level annotations, which are very labor-demanding and error-prone to obtain, here we focus on training models using only patch-level labels (e.g. a single field of view within an entire mosaic). We segment RCM mosaics into "benign" and "aspecific (nonspecific)" regions, where aspecific regions represent the loss of regular architecture due to injury and/or inflammation, pre-malignancy, or malignancy. We adopt Efficientnet, a deep neural network (DNN) proven to accurately accomplish classification tasks, to generate class activation maps, and use a Gaussian weighting kernel to stitch smaller images back into larger fields of view. The trained DNN achieved an average area under the curve of 0.969, and Dice coefficient of 0.778 showing the feasibility of spatial localization of aspecific regions in RCM images, and making the diagnostics decision model more interpretable to the clinicians. [ABSTRACT FROM AUTHOR]

The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis. [ABSTRACT FROM AUTHOR]

Blood cell count provides relevant clinical information about different kinds of disorders. Any deviation in the number of blood cells implies the presence of infection, inflammation, edema, bleeding, and other blood-related issues. Current microscopic methods used for blood cell counting are very tedious and are highly prone to different sources of errors. Besides, these techniques do not provide full information related to blood cells like shape and size, which play important roles in the clinical investigation of serious blood-related diseases. In this paper, deep learning-based automatic classification and quantitative analysis of blood cells are proposed using the YOLOv2 model. The model was trained on 1560 images and 2703-labeled blood cells with different hyper-parameters. It was tested on 26 images containing 1454 red blood cells, 159 platelets, 3 basophils, 12 eosinophils, 24 lymphocytes, 13 monocytes, and 28 neutrophils. The network achieved detection and segmentation of blood cells with an average accuracy of 80.6% and a precision of 88.4%. Quantitative analysis of cells was done following classification, and mean accuracy of 92.96%, 91.96%, 88.736%, and 92.7% has been achieved in the measurement of area, aspect ratio, diameter, and counting of cells respectively. Graphical abstract [ABSTRACT FROM AUTHOR]

Aim and objective: Emerging translational evidence suggests that epigenetic alterations (DNA methylation, miRNA expression, and histone modifications) occur after external stimuli and may contribute to exacerbated inflammation and the risk of suffering several diseases including diabetes, cardiovascular diseases, cancer, and neurological disorders. This review summarizes the current knowledge about the harmful effects of high-fat/high-sugar diets, micronutrient deficiencies (folate, manganese, and carotenoids), obesity and associated complications, bacterial/viral infections, smoking, excessive alcohol consumption, sleep deprivation, chronic stress, air pollution, and chemical exposure on inflammation through epigenetic mechanisms. Additionally, the epigenetic phenomena underlying the anti-inflammatory potential of caloric restriction, n-3 PUFA, Mediterranean diet, vitamin D, zinc, polyphenols (i.e., resveratrol, gallic acid, epicatechin, luteolin, curcumin), and the role of systematic exercise are discussed. Methods: Original and review articles encompassing epigenetics and inflammation were screened from major databases (including PubMed, Medline, Science Direct, Scopus, etc.) and analyzed for the writing of the review paper. Conclusion: Although caution should be exercised, research on epigenetic mechanisms is contributing to understand pathological processes involving inflammatory responses, the prediction of disease risk based on the epigenotype, as well as the putative design of therapeutic interventions targeting the epigenome. [ABSTRACT FROM AUTHOR]

This paper presents a brief overview of the complex interaction between age, hypertension, the renin–angiotensin–aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, 'inflammaging', which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: This study was to evaluate the diagnostic value of liver extracellular volume (LECV) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (NASH).Methods: Forty-eight cynomolgus monkeys were enrolled in this prospective study. There are 17 healthy monkeys and 31 monkeys with NASH. Ten of these monkeys were used for repeatability assessment. The remaining 38 monkeys were used to compare LECV with other indicators including pathology fibrosis score, native T1, and serum chemical indexes by Spearman, Pearson correlation test, and ROC curves. The inter-reader variability was assessed by interclass correlation. The repeatability measurement of LECV was analyzed using Bland-Altman plots and the coefficient of variation. Partial correlation analysis was performed to assess the effects of fat content and inflammation scores on the correlation between LECV/T1 and liver fibrosis score.Results: This study demonstrated a good intra-reader agreement (intraclass correlation = 0.79) of LECV in all monkeys and an excellent repeatability in 10 monkeys (coefficient of variation = 2.01%). The LECV has a strong correlation with the fibrosis score (r = 0.949; p < 0.0001), low-density lipoprotein (r = 0.72; p < 0.0001), and cholesterol (r = 0.70; p < 0.0001). LECV showed high diagnostic efficacy in the diagnosis of liver fibrosis (area under the curve of ROC, 0.945~1; p < 0.001).Conclusions: LECV may serve as a noninvasive valuable biomarker for the quantification and differentiating of the non-severe liver fibrosis (stage ≤ F3). However, circulating serum markers low-density lipoprotein and cholesterol (CHO) may not serve for this purpose.Key Points: • This paper demonstrated the excellent repeatability (intraclass correlation coefficient = 0.79) of LECV in monkey animal model. • LECV-MRI has a strong correlation with histopathological fibrosis score stage (r = 0.949; p < 0.0001) and shows high diagnostic efficacy in the staging of non-severe liver fibrosis (the area under ROC curve ≥ 0.945). • The new fibrosis score maps appeared to provide a better imaging tool for the spatial assessment of liver fibrosis. It may eventually facilitate the diagnosis of liver fibrosis distribution. [ABSTRACT FROM AUTHOR]

Melatonin has been used perioperative to control pain, inflammation, and oxidative stress. The present paper aims to evaluate the effect of the administration of melatonin on acute phase proteins and inflammatory cytokines and compare the trends after the melatonin administration in intact and castrated dogs. Twenty healthy mature male dogs (1–3 years old) were divided randomly into 4 groups (n = 5): melatonin, castrated and melatonin, castrated, and control. Melatonin (3 mg capsule/10 kg) was administrated every 24 h for 1 month and castration was performed on day 0. Blood was collected from each dog's jugular vein every 7 days during this period. The serum samples were tested for hormonal assay using ELISA methods. Proteins and inflammatory cytokines (α-1 acid glycoprotein (AGP), serum amyloid-A (SAA), C-reactive protein (CRP), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) usually elevated in the first few days after surgery and returned to normal about 7 days after the surgery. During the study, the use of melatonin in castrated dogs significantly reduced the inflammatory proteins and cytokines, but in intact dogs, it did not significantly change the proteins and inflammatory cytokines. Daily intake of melatonin capsules in dogs may be beneficial in reducing inflammation by affecting the concentration of proteins and inflammatory cytokines released after castration surgery. [ABSTRACT FROM AUTHOR]

Recent findings from our laboratory highlight the role of the modulation of the innate immune function and systemic inflammatory response in the effectiveness of balneotherapy in rheumatic diseases, specifically in elderly patients with osteoarthritis. Immune-neuroendocrine and stress mediators are involved in these effects. The 'bioregulatory effect of balneotherapy' has also been recently proposed as a mechanism of effectiveness that consists of a reduction in systemic pro-inflammatory mediators together with the achievement of an optimal innate response through stimulation (or at least lack of impairment) of the innate defences against pathogens (i.e. phagocytosis, microbicide activity) mediated by neutrophils, also generating immunophysiological adaptations through an optimal balance between the pro- and the anti-inflammatory responses in which regulatory T cells seem to have a crucial role. In the present paper, we aim to analyse the main conclusions related to how balneotherapy with the use of peloids (pelotherapy) affects the innate and inflammatory responses, constituting an immunophysiological mechanism underlying the proven clinical benefits of this intervention. We also introduce novel results regarding the innate response (phagocytic process) of monocytes in this therapy, an inflammatory cell that has not yet been studied in this context. Increased chemotaxis together with a decline in oxidative burst, without changes in phagocytosis, could be the main response induced by this modality of balneological intervention. [ABSTRACT FROM AUTHOR]

Depression and anxiety are comorbid conditions in many neurological or psychopathological disorders. Stress is an underlying event that triggers development of anxiety and depressive-like behaviors. Recent experimental data indicate that anxiety and depressive-like behaviors occurring as a result of stressful situations can cause blood–brain barrier (BBB) dysfunction, which is characterized by inflammation and leakage. However, the underlying mechanisms are not completely understood. This paper sought to review recent experimental preclinical and clinical data that suggest possible molecular mechanisms involved in development of stress-induced anxiety and depression with associated BBB inflammation and leakage. Critical therapeutic targets and potential pharmacological candidates for treatment of stress-induced anxiety and depression with associated BBB dysfunctions are also discussed. [ABSTRACT FROM AUTHOR]

Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose–response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage also increase inflammation. Inflammation contributes to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS and DNA damage, and separately increases proliferation and breast cancer through pro-carcinogenic effects on cells and tissue. For example, gene expression changes alter inflammatory mediators, resulting in improved survival and growth of cancer cells and a more hospitable tissue environment. All of these events overlap at multiple points with events characteristic of "background" induction of breast carcinogenesis, including hormone-responsive proliferation, oxidative activity, and DNA damage. These overlaps make the breast particularly susceptible to ionizing radiation and reinforce that these biological activities are important characteristics of carcinogens. Agents that increase these biological processes should be considered potential breast carcinogens, and predictive methods are needed to identify chemicals that increase these processes. Techniques are available to measure RONS, DNA damage and mutation, cell proliferation, and some inflammatory proteins or processes. Improved assays are needed to measure GI and chronic inflammation, as well as the interaction with hormonally driven development and proliferation. Several methods measure diverse epigenetic changes, but it is not clear which changes are relevant to breast cancer. In addition, most toxicological assays are not conducted in mammary tissue, and so it is a priority to evaluate if results from other tissues are generalizable to breast, or to conduct assays in breast tissue. Developing and applying these assays to identify exposures of concern will facilitate efforts to reduce subsequent breast cancer risk. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis (AIP) is an inflammatory process of the pancreas that occurs most commonly in elderly males and clinically can mimic pancreatic adenocarcinoma and present with jaundice, weight loss, and abdominal pain. Mass-forming lesions in the pancreas are seen in the focal form of AIP and both clinical and imaging findings can overlap those of pancreatic cancer. The accurate distinction of AIP from pancreatic cancer is of utmost importance as it means avoiding unnecessary surgery in AIP cases or inaccurate steroid treatment in patients with pancreatic cancer. Imaging concomitantly with serological examinations (IgG4 and Ca 19-9) plays an important role in the distinction between these entities. Characteristic extra-pancreatic manifestations as well as favorable good response to treatment with steroids are characteristic of AIP. This paper will review current diagnostic parameters useful in differentiating between focal AIP and pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Purpose: No study has summarized earlier findings on the effect of probiotic supplementation on inflammatory biomarkers. This systematic review and meta-analysis was conducted to systematically review the available placebo-controlled clinical trials about the effect of probiotic supplementation on several inflammatory biomarkers in adults. Methods: Relevant papers published up to March 2018 were searched up through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar, using following suitable keywords. Clinical trials that examined the effect of probiotic supplementation on inflammation in adults were included. Results: Overall, 42 randomized clinical trials (1138 participants in intervention and 1120 participants in control groups) were included. Combining findings from included studies, we found a significant reduction in serum hs-CRP [standardized mean difference (SMD) − 0.46; 95% CI − 0.73, − 0.19], TNF-a (− 0.21; − 0.34, − 0.08), IL-6 (− 0.37; − 0.51, − 0.24), IL-12 (− 0.47; − 0.67, − 0.27), and IL-4 concentrations (− 0.48; − 0.76, − 0.20) after probiotic supplementation. Pooling effect sizes from 11 studies with 12 effect sizes, a significant increase in IL-10 concentrations was seen (0.21; 0.04, 0.38). We failed to find a significant effect of probiotic supplementation on serum IL-1B (− 0.17; − 0.37, 0.02), IL-8 (− 0.01; − 0.30, 0.28), and IFN-g (− 0.08; − 0.31, 0.15) and IL-17 concentrations (0.06; − 0.34, 0.46). Conclusions: Probiotic supplementation significantly reduced serum concentrations of pro-inflammatory cytokines including, hs-CRP, TNF-a, IL-6, IL-12, and IL-4, but it did not influence IL-1B, IL-8, IFN-g, and IL-17 concentrations. A significant increase in serum concentrations of IL-10, as a anti-inflammatory cytokine was also documented after probiotic supplementation. [ABSTRACT FROM AUTHOR]

Purpose: This clinical concepts paper discusses the essential elements of cruciate ligament recuperation, micro-trauma repair, and remodeling.Methods: Cruciate ligament mechanobiology and tissue heterogeneity, anatomy and vascularity, and synovial membrane and fluid functions are discussed in relationship to deficiency-induced inflammatory responses, nervous and immune system function, recuperation, repair and remodeling, and modern threats to homeostasis.Results: Cruciate ligament surgical procedures do not appreciate the vital linked functions of the central, peripheral, and autonomic nervous systems and immune system function on knee ligament injury recuperation, micro-trauma repair, and remodeling. Enhanced knowledge of these systems could provide innovative ways to decrease primary non-contact knee injury rates and improve outcomes following reconstruction or primary repair.Conclusions: Restoration of knee joint homeostasis is essential to cruciate ligament recuperation, micro-trauma repair, and remodeling. The nervous and immune systems are intricately involved in this process. Varying combinations of high-intensity training, under-recovery, technostress, and environmental pollutants (including noise) regularly expose many athletically active individuals to factors that abrogate the environment needed for cruciate ligament recuperation, micro-trauma repair, and remodeling. Current sports training practice, lifestyle psychobehaviors, and environmental factors combine to increase both primary non-contact knee injury risk and the nervous and immune system dysregulation that lead to poor sleep, increased anxiety, and poorly regulated hormone and cytokine levels. These factors may create a worst-case scenario leading to poor ligament recuperation, micro-trauma repair, and remodeling. Early recognition and modification of these factors may decrease knee ligament injury rates and improve cruciate ligament repair or reconstruction outcomes.Level Of Evidence: V. [ABSTRACT FROM AUTHOR]