The impact of arthritogenic viruses in oral tissues.

Arthritis and periodontitis are inflammatory diseases that share several immunopathogenic features. The expansion in the study of virus-induced arthritis has shed light on how this condition could impact other parts of the human body, including the mouth. Viral arthritis is an inflammatory joint disease caused by several viruses, most notably the alphaviruses Chikungunya virus (CHIKV), Sindbis virus (SINV), Ross River virus (RRV), Mayaro virus (MAYV), and O'nyong'nyong virus (ONNV). These viruses can induce an upsurge of matrix metalloproteinases and immune-inflammatory mediators such as Interleukin-6 (IL6), IL-1ß, tumor necrosis factor, chemokine ligand 2, and receptor activator of nuclear factor kappa-B ligand in the joint and serum of infected individuals. This can lead to the influx of inflammatory cells to the joints and associated muscles as well as osteoclast activation and differentiation, culminating in clinical signs of swelling, pain, and bone resorption. Moreover, several data indicate that these viral infections can affect other sites of the body, including the mouth. The human oral cavity is a rich and diverse microbial ecosystem, and viral infection can disrupt the balance of microbial species, causing local dysbiosis. Such events can result in oral mucosal damage and gingival bleeding, which are indicative of periodontitis. Additionally, infection by RRV, CHIKV, SINV, MAYV, or ONNV can trigger the formation of osteoclasts and upregulate pro-osteoclastogenic inflammatory mediators, interfering with osteoclast activation. As a result, these viruses may be linked to systemic conditions, including oral manifestations. Therefore, this review focuses on the involvement of alphavirus infections in joint and oral health, acting as potential agents associated with oral mucosal inflammation and alveolar bone loss. The findings of this review demonstrate how alphavirus infections could be linked to the comorbidity between arthritis and periodontitis and may provide a better understanding of potential therapeutic management for both conditions.

Comparison between transradial and transfemoral mechanical thrombectomy for ICA and M1 occlusions: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: The role for the transradial approach for mechanical thrombectomy is controversial. We sought to compare transradial and transfemoral mechanical thrombectomy in a large multicenter database of acute ischemic stroke. METHODS: The prospectively maintained Stroke Thrombectomy and Aneurysm Registry (STAR) was reviewed for patients who underwent mechanical thrombectomy for an internal carotid artery (ICA) or middle cerebral artery M1 occlusion. Multivariate regression analyses were performed to assess outcomes including reperfusion time, symptomatic intracerebral hemorrhage (ICH), distal embolization, and functional outcomes. RESULTS: A total of 2258 cases, 1976 via the transfemoral approach and 282 via the transradial approach, were included. Radial access was associated with shorter reperfusion time (34.1 min vs 43.6 min, P=0.001) with similar rates of Thrombolysis in Cerebral Infarction (TICI) 2B or greater reperfusion (87.9% vs 88.1%, P=0.246). Patients treated via a transradial approach were more likely to achieve at least TICI 2C (59.6% vs 54.7%, P=0.001) and TICI 3 reperfusion (50.0% vs 46.2%, P=0.001), and had shorter lengths of stay (mean 9.2 days vs 10.2, P<0.001). Patients treated transradially had a lower rate of symptomatic ICH (8.0% vs 9.4%, P=0.047) but a higher rate of distal embolization (23.0% vs 7.1%, P<0.001). There were no significant differences in functional outcome at 90 days between the two groups. CONCLUSIONS: Radial and femoral thrombectomy resulted in similar clinical outcomes. In multivariate analysis, the radial approach had improved revascularization rates, fewer cases of symptomatic ICH, and faster reperfusion times, but higher rates of distal emboli. Further studies on the optimal approach are necessary based on patient and disease characteristics.

Outcomes of mechanical thrombectomy in stroke patients with extreme large infarction core.

BACKGROUND: Recent clinical trials have demonstrated that patients with large vessel occlusion (LVO) and large infarction core may still benefit from mechanical thrombectomy (MT). In this study, we evaluate outcomes of MT in LVO patients presenting with extremely large infarction core Alberta Stroke Program Early CT Score (ASPECTS 0-2). METHODS: Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) was interrogated. We identified thrombectomy patients presenting with an occlusion in the intracranial internal carotid artery (ICA) or M1 segment of the middle cerebral artery and extremely large infarction core (ASPECTS 0-2). A favorable outcome was defined by achieving a modified Rankin scale of 0-3 at 90 days post-MT. Successful recanalization was defined by achieving a modified Thrombolysis In Cerebral Ischemia (mTICI) score ≥2B. RESULTS: We identified 58 patients who presented with ASPECTS 0-2 and underwent MT . Median age was 70.0 (59.0-78.0) years, 45.1% were females, and 202 (36.3%) patients received intravenous tissue plasminogen activator. There was no difference regarding the location of the occlusion (p=0.57). Aspiration thrombectomy was performed in 268 (54.6%) patients and stent retriever was used in 70 (14.3%) patients. In patients presenting with ASPECTS 0-2 the mortality rate was 4.5%, 27.9% had mRS 0-3 at day 90, 66.67% ≥70 years of age had mRS of 5-6 at day 90. On multivariable analysis, age, National Institutes of Health Stroke Scale on admission, and successful recanalization (mTICI ≥2B) were independently associated with favorable outcomes. CONCLUSIONS: This multicentered, retrospective cohort study suggests that MT may be beneficial in a select group of patients with ASPECTS 0-2.

Predictors of parenchymal hematoma and clinical outcome after mechanical thrombectomy in patients with large ischemic core due to large vessel occlusion: a retrospective multicenter study.

BACKGROUND: The aim of our study was to find predictors of parenchymal hematoma (PH) and clinical outcome after mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) and baseline large infarct. METHODS: The databases of 16 stroke centers were retrospectively screened for patients with anterior circulation LVO and baseline Alberta Stroke Program Early CT Score (ASPECTS) ≤5 that received MT. Procedural parameters, including the number of passes during first and second technique of MT, were recorded. Outcome measures were occurrence of PH type 2 and any type of PH after MT, and the 90-day modified Rankin Scale (mRS) score of 0-3 and 0-2. RESULTS: In total, 408 patients were available for analysis. A higher number of passes in the second technique was predictive of PH type 2 (odds ratio (OR) - 3.204, 95% confidence interval (CI) 1.140 to 9.005), whereas procedure conducted under general anesthesia was associated with lower risk (OR 0.127, 95% CI 0.002 to 0.808). The modified thrombolysis in cerebral infarction grade 2c-3 was associated with the mRS score 0-3 (OR 3.373, 95% CI 1.891 to 6.017), whereas occurrence of PH type 2 was predictive of unfavorable outcome (OR 0.221, 95% CI 0.063 to 0.773). Similar results were found for the mRS score 0-2 outcome measure. CONCLUSION: In patients with large ischemic core, a higher number of passes during MT and procedure not conducted under general anesthesia are associated with increased rate of PH type 2, that negatively impact the clinical outcome. Our data outline a delicate balance between the need of a complete recanalization and the risk of PH following MT.

Mechanical thrombectomy for the treatment of primary and secondary anterior cerebral artery occlusions: insights from STAR.

BACKGROUND: The safety and efficacy of mechanical thrombectomy (MT) for the treatment of acute anterior cerebral artery (ACA) occlusions have not clearly been delineated. Outcomes may be impacted based on whether the occlusion is isolated to the ACA (primary ACA occlusion) or occurs in conjunction with other cerebral arteries (secondary). METHODS: We performed a retrospective review of the multicenter Stroke Thrombectomy and Aneurysm (STAR) database. All patients with MT-treated primary or secondary ACA occlusions were included. Baseline characteristics, procedural outcomes, complications, and clinical outcomes were collected. Primary and secondary ACA occlusions were compared using the Mann-Whitney U test and Kruskal-Willis test for continuous variables and the χ2 test for categorical variables. RESULTS: The study cohort comprised 238 patients with ACA occlusions (49.2% female, median (SD) age 65.6 (16.7) years). The overall rate of successful recanalization was 75%, 90-day good functional outcome was 23%, and 90-day mortality was 35%. There were 44 patients with a primary ACA occlusion and 194 patients with a secondary ACA occlusion. When adjusted for baseline variables, the rates of successful recanalization (68% vs 76%, P=0.27), 90-day good functional outcome (41% vs 19%, P=0.38), and mortality at 90 days (25% vs 38%, P=0.12) did not differ between primary and secondary ACA occlusion groups. CONCLUSION: Clinical and procedural outcomes are similar between MT-treated primary and secondary ACA occlusions for select patients. Our findings demonstrate the need for established criteria to determine ideal patient and ACA stroke characteristics amenable to MT treatment.

Comparison of balloon guide catheter versus non-balloon guide catheter for mechanical thrombectomy in patients with distal medium vessel occlusion.

BACKGROUND: Several studies have established the safety and efficacy of balloon guide catheters (BGCs) for large vessel occlusions. However, the utility of BGCs remains largely unexplored for distal medium vessel occlusions (DMVOs). In this study, we aim to compare the outcomes of BGC vs. Non-BGC in patients undergoing mechanical thrombectomy (MT) for DMVO. METHOD: This retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) encompassed adult patients with acute anterior cerebral artery, posterior cerebral artery, and middle cerebral artery-M2-3-4 occlusions. Procedure times, safety, recanalization, and neurological outcomes were compared between the two groups, with subgroup analysis based on first-line thrombectomy techniques. RESULTS: A total of 1508 patients were included, with 231 patients (15.3%) in the BGC group and 1277 patients (84.7%) in the non-BGC group. The BGC group had a lower modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2C (43.2% vs 52.7%, P=0.01), longer time from puncture to intracranial access (15 vs 8 min, P<0.01), and from puncture to final recanalization (97 vs 34 min, P<0.01). In the Solumbra subgroup, the first pass effect (FPE) rate was lower in the BGC group (17.4% vs 30.7%, P=0.03). Regarding clinical outcomes, the BGC group had a lower rate of distal embolization (8.8% vs 14.9%, P=0.03). CONCLUSION: Our study found that use of BGC in patients with DMVO was associated with lower mTICI scores, decreased FPE rates, reduced distal embolization, and longer procedure times.

Perfluorocarbons in Research and Clinical Practice: A Narrative Review.

Perfluorocarbons (PFCs) are organic liquids derived from hydrocarbons in which some of the hydrogen atoms have been replaced by fluorine atoms. They are chemically and biologically inert substances with a good safety profile. They are stable at room temperature, easy to store, and immiscible in water. Perfluorocarbons have been studied in biomedical research since 1960 for their unique properties as oxygen carriers. In particular, PFCs have been used for liquid ventilation in unusual environments such as deep-sea diving and simulations of zero gravity, and more recently for drug delivery and diagnostic imaging. Additionally, when delivered as emulsions, PFCs have been used as red blood cell substitutes. This narrative review will discuss the multifaceted utilization of PFCs in therapeutics, diagnostics, and research. We will specifically emphasize the potential role of PFCs as red blood cell substitutes, as airway mechanotransducers during artificial placenta procedures, as a means to improve donor organ perfusion during the ex vivo assessment, and as an adjunct in cancer therapies because of their ability to reduce local tissue hypoxia.

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review.

Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies.

Label-free liquid biopsy through the identification of tumor cells by machine learning-powered tomographic phase imaging flow cytometry.

Image-based identification of circulating tumor cells in microfluidic cytometry condition is one of the most challenging perspectives in the Liquid Biopsy scenario. Here we show a machine learning-powered tomographic phase imaging flow cytometry system capable to provide high-throughput 3D phase-contrast tomograms of each single cell. In fact, we show that discrimination of tumor cells against white blood cells is potentially achievable with the aid of artificial intelligence in a label-free flow-cyto-tomography method. We propose a hierarchical machine learning decision-maker, working on a set of features calculated from the 3D tomograms of the cells' refractive index. We prove that 3D morphological features are adequately distinctive to identify tumor cells versus the white blood cell background in the first stage and, moreover, in recognizing the tumor type at the second decision step. Proof-of-concept experiments are shown, in which two different tumor cell lines, namely neuroblastoma cancer cells and ovarian cancer cells, are used against monocytes. The reported results allow claiming the identification of tumor cells with a success rate higher than 97% and with an accuracy over 97% in discriminating between the two cancer cell types, thus opening in a near future the route to a new Liquid Biopsy tool for detecting and classifying circulating tumor cells in blood by stain-free method.

Early neurological deterioration in patients with minor stroke due to isolated M2 occlusion undergoing medical management: a retrospective multicenter study.

BACKGROUND: Patients with minor stroke and M2 occlusion undergoing best medical management (BMM) may face early neurological deterioration (END) that can lead to poor long-term outcome. In case of END, rescue mechanical thrombectomy (rMT) seems beneficial. Our study aimed to define factors relevant to clinical outcome in patients undergoing BMM with the possibility of rMT on END, and find predictors of END. METHODS: Patients with M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score≤5 that received either BMM only or rMT on END after BMM were extracted from the databases of 16 comprehensive stroke centers. Clinical outcome measures were a 90-day modified Rankin Scale (mRS) score of 0-1 or 0-2, and occurrence of END. RESULTS: Among 10 169 consecutive patients with large vessel occlusion admitted between 2016 and 2021, 208 patients were available for analysis. END was reported in 87 patients that were therefore all subjected to rMT. In a logistic regression model, END (OR 3.386, 95% CI 1.428 to 8.032), baseline NIHSS score (OR 1.362, 95% CI 1.004 to 1.848) and a pre-event mRS score=1 (OR 3.226, 95% CI 1.229 to 8.465) were associated with unfavorable outcome. In patients with END, successful rMT was associated with favorable outcome (OR 4.549, 95% CI 1.098 to 18.851). Among baseline clinical and neuroradiological features, presence of atrial fibrillation was a predictor of END (OR 3.547, 95% CI 1.014 to 12.406). CONCLUSION: Patients with minor stroke due to M2 occlusion and atrial fibrillation should be closely monitored for possible worsening during BMM and, in this case, promptly considered for rMT.

Risk factors and predictors of intracranial hemorrhage after mechanical thrombectomy in acute ischemic stroke: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR).

BACKGROUND: Reducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy. METHODS: This is a retrospective review of the Stroke Thrombectomy and Aneurysm Registry (STAR) database. All patients who underwent AIS thrombectomy with available ICH data were included. Multivariable regression models were developed to identify predictors of ICH after thrombectomy. Subgroup analyses were performed stratified by symptom status and European Cooperative Acute Stroke Study (ECASS) grade. RESULTS: The study cohort comprised 6860 patients. Any ICH and symptomatic ICH (sICH) occurred in 25% and 7% of patients, respectively. Hemorrhagic infarction 1 (HI1) occurred in 36%, HI2 in 24%, parenchymal hemorrhage 1 (PH1) in 22%, and PH2 in 17% of patients classified by ECASS grade. Intraprocedural complications independently predicted any ICH (OR 3.8083, P<0.0001), PH1 (OR 1.9053, P=0.0195), and PH2 (OR 2.7347, P=0.0004). Race also independently predicted any ICH (black: OR 0.5180, P=0.0017; Hispanic: OR 0.4615, P=0.0148), sICH (non-white: OR 0.4349, P=0.0107), PH1 (non-white: OR 3.1668, P<0.0001), and PH2 (non-white: OR 1.8689, P=0.0176), with white as the reference. Primary mechanical thrombectomy technique also independently predicted ICH. ADAPT (A Direct Aspiration First Pass Technique) was a negative predictor of sICH (OR 0.2501, P<0.0001), with stent retriever as the reference. CONCLUSIONS: This study identified ICH risk factors after AIS thrombectomy using real-world data. There was a propensity towards a reduced sICH risk with direct aspiration. Procedural complications and ethnicity were predictors congruent between categories of any ICH, sICH, PH1, and PH2. Further investigation of technique and ethnicity effects on ICH and outcomes after AIS thrombectomy is warranted.

Mechanical thrombectomy for large vessel occlusion strokes beyond 24 hours.

BACKGROUND: Recent clinical trials have shown that mechanical thrombectomy is superior to medical management for large vessel occlusion for up to 24 hours from onset. Our objective is to examine the safety and efficacy of thrombectomy beyond the standard of care window. METHODS: A retrospective review was undertaken of the multicenter Stroke Thrombectomy and Aneurysm Registry (STAR). We identified patients who underwent mechanical thrombectomy for large vessel occlusion beyond 24 hours. We selected a matched control group from patients who underwent thrombectomy in the 6-24-hour window. We used functional independence at 3 months as our primary outcome measure. RESULTS: We identified 121 patients who underwent thrombectomy beyond 24 hours and 1824 in the 6-24-hour window. We selected a 2:1 matched group of patients with thrombectomy 6-24 hours as a comparison group. Patients undergoing thrombectomy beyond 24 hours were less likely to be independent at 90 days (18 (18.8%) vs 73 (34.9%), P=0.005). They had higher odds of mortality at 90 days in the adjusted analysis (OR 2.34, P=0.023). Symptomatic intracerebral hemorrhage and other complications were similar in the two groups. In a multivariate analysis only lower number of attempts was associated with good outcomes (OR 0.27, P=0.022). CONCLUSIONS: Mechanical thrombectomy beyond 24 hours appears to be safe and tolerable with no more hemorrhages or complications compared with standard of care thrombectomy. Outcomes and mortality in this time window are worse compared with an earlier time window, but the rates of good outcomes may justify this therapy in selected patients.

Mechanical thrombectomy in minor stroke due to isolated M2 occlusion: a multicenter retrospective matched analysis.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of mechanical thrombectomy (MT) in patients with isolated M2 occlusion and minor symptoms and identify possible baseline predictors of clinical outcome. METHODS: The databases of 16 high-volume stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤5 who received either early MT (eMT) or best medical management (BMM) with the possibility of rescue MT (rMT) on early neurological worsening. Because our patients were not randomized, we used propensity score matching (PSM) to estimate the treatment effect of eMT compared with the BMM/rMT. The primary clinical outcome measure was a 90-day modified Rankin Scale score of 0-1. RESULTS: 388 patients were initially selected and, after PSM, 100 pairs of patients receiving eMT or BMM/rMT were available for analysis. We found no significant differences in clinical outcome and in safety measures between patients receiving eMT or BMM/rMT. Similar results were also observed after comparison between eMT and rMT. Concerning baseline predicting factors of outcome, the involvement of the M2 inferior branch was associated with a favorable outcome. CONCLUSION: Our multicenter retrospective analysis has shown no benefit of eMT in minor stroke patients with isolated M2 occlusion over a more conservative therapeutic approach. Although our results must be viewed with caution, in these patients it appears reasonable to consider BMM as the first option and rMT in the presence of early neurological deterioration.

Radiomics and artificial intelligence in prostate cancer: new tools for molecular hybrid imaging and theragnostics.

In prostate cancer (PCa), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance strategies, and introduced specific and personalized radioreceptor therapies. Nuclear medicine, therefore, holds great promise for improving the quality of life of PCa patients, through managing and processing a vast amount of molecular imaging data and beyond, using a multi-omics approach and improving patients' risk-stratification for tailored medicine. Artificial intelligence (AI) and radiomics may allow clinicians to improve the overall efficiency and accuracy of using these "big data" in both the diagnostic and theragnostic field: from technical aspects (such as semi-automatization of tumor segmentation, image reconstruction, and interpretation) to clinical outcomes, improving a deeper understanding of the molecular environment of PCa, refining personalized treatment strategies, and increasing the ability to predict the outcome. This systematic review aims to describe the current literature on AI and radiomics applied to molecular imaging of prostate cancer.

Anti-Zika Virus Activity of Plant Extracts Containing Polyphenols and Triterpenes on Vero CCL-81 and Human Neuroblastoma SH-SY5Y Cells.

Zika virus (ZIKV) infection is a global threat associated to neurological disorders in adults and microcephaly in children born to infected mothers. No vaccine or drug is available against ZIKV. We herein report the anti-ZIKV activity of 36 plant extracts containing polyphenols and/or triterpenes. ZIKV-infected Vero CCL-81 cells were treated with samples at non-cytotoxic concentrations, determined by MTT and LDH assays. One third of the extracts elicited concentration-dependent anti-ZIKV effect, with viral loads reduction from 0.4 to 3.8 log units. The 12 active extracts were tested on ZIKV-infected SH-SY5Y cells and significant reductions of viral loads (in log units) were induced by Maytenus ilicifolia (4.5 log), Terminalia phaeocarpa (3.7 log), Maytenus rigida (1.7 log) and Echinodorus grandiflorus (1.7 log) extracts. Median cytotoxic concentration (CC50 ) of these extracts in Vero cells were higher than in SH-SY5Y lineage. M. ilicifolia (IC50 =16.8±10.3 µg/mL, SI=3.4) and T. phaeocarpa (IC50 =22.0±6.8 µg/mL, SI=4.8) were the most active extracts. UPLC-ESI-MS/MS analysis of M. ilicifolia extract led to the identification of 7 triterpenes, of which lupeol and a mixture of friedelin/friedelinol showed no activity against ZIKV. The composition of T. phaeocarpa extract comprises phenolic acids, ellagitannins and flavonoids, as recently reported by us. In conclusion, the anti-ZIKV activity of 12 plant extracts is here described for the first time and polyphenols and triterpenes were identified as the probable bioactive constituents of T. phaeocarpa and M. ilicifolia, respectively.

Mitochondrial DNA as a Possible Ligand for TLR9 in Irinotecan-induced Small Intestinal Mucositis.

Cancer chemotherapy and radiotherapy may result in mucositis characterized by stem cell damage and inflammation in the gastrointestinal tract. The molecular mechanisms underlying this pathology remain unknown. Based on the assumption that mitochondrial CPG-DNA (mtDNA) released and sensed by TLR9 could underlie mucositis pathology, we analyzed the mtDNA levels in sera as well as inflammatory and disease parameters in the small intestine from wild-type (WT) and TLR9-deficient mice (TLR9-/-) in an experimental model of intestinal mucositis induced by irinotecan. Additionally, we verified the ability of WT and TLR9-/- macrophages to respond to CpG-DNA in vitro. WT mice injected with irinotecan presented a progressive increase in mtDNA in the serum along with increased hematocrit, shortening of small intestine length, reduction of intestinal villus:crypt ratio and increased influx of neutrophils, which were followed by higher expression of Nlrp3 and Casp1 mRNA and increased IL-1ß levels in the ileum when compared to vehicle-injected mice. TLR9-deficient mice were protected in all these parameters when compared to WT mice. Furthermore, TLR9 was required for the production of IL-1ß and NO after macrophage stimulation with CpG-DNA. Overall, our findings show that the amount of circulating free CpG-DNA is increased upon chemotherapy and that TLR9 activation is important for NLRP3 inflammasome transcription and further IL-1ß release, playing a central role in the development of irinotecan-induced intestinal mucositis. We suggest that TLR9 antagonism may be a new therapeutic strategy for limiting irinotecan-induced intestinal inflammation.

Eosinophil plays a crucial role in intestinal mucositis induced by antineoplastic chemotherapy.

Mucositis is a major clinical complication associated with cancer treatment and may limit the benefit of chemotherapy. Leukocytes and inflammatory mediators have been extensively associated with mucositis severity. However, the role of eosinophils in the pathophysiology of chemotherapy-induced mucositis remains to be elucidated. Here, using GATA-1-deficient mice, we investigated the role of eosinophils in intestinal mucositis. There was marked accumulation of eosinophils in mice given irinotecan and eosinophil ablation inhibited intestinal mucositis. Treatment with Evasin-4, a chemokine receptor antagonist, reduced the recruitment of eosinophils and decreased irinotecan-induced mucositis. Importantly, Evasin-4 did not interfere negatively with the antitumour effects of irinotecan. Evasin-4 was of benefit for mice given high doses of irinotecan once Evasin-4-treated mice presented delayed mortality. Altogether, our findings suggest that Evasin-4 may have significant mucosal-protective effects in the context of antineoplastic chemotherapy and may, therefore, be useful in combination with anticancer treatment in cancer patients.

cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice.

cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1ß levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

Finding intracellular lipid droplets from the single-cell biolens' signature in a holographic flow-cytometry assay.

In recent years, intracellular LDs have been discovered to play an important role in several pathologies. Therefore, detection of LDs would provide an in-demand diagnostic tool if coupled with flow-cytometry to give significant statistical analysis and especially if the diagnosis is made in full non-invasive mode. Here we combine the experimental results of in-flow tomographic phase microscopy with a suited numerical simulation to demonstrate that intracellular LDs can be easily detected through a label-free approach based on the direct analysis of the 2D quantitative phase maps recorded by a holographic flow cytometer. In fact, we demonstrate that the presence of LDs affects the optical focusing lensing features of the embracing cell, which can be considered a biological lens. The research was conducted on white blood cells (i.e., lymphocytes and monocytes) and ovarian cancer cells. Results show that the biolens properties of cells can be a rapid biomarker that aids in boosting the diagnosis of LDs-related pathologies by means of the holographic flow-cytometry assay for fast, non-destructive, and high-throughput screening of statistically significant number of cells.

Protective Response in Experimental Paracoccidioidomycosis Elicited by Extracellular Vesicles Containing Antigens of Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM) is a systemic disease caused by Paracoccidioides spp. PCM is endemic in Latin America and most cases are registered in Brazil. This mycosis affects mainly the lungs, but can also spread to other tissues and organs, including the liver. Several approaches have been investigated to improve treatment effectiveness and protection against the disease. Extracellular vesicles (EVs) are good antigen delivery vehicles. The present work aims to investigate the use of EVs derived from Paracoccidioides brasiliensis as an immunization tool in a murine model of PCM. For this, male C57BL/6 were immunized with two doses of EVs plus adjuvant and then infected with P. brasiliensis. EV immunization induced IgM and IgG in vivo and cytokine production by splenocytes ex vivo. Further, immunization with EVs had a positive effect on mice infected with P. brasiliensis, as it induced activated T lymphocytes and NKT cell mobilization to the infected lungs, improved production of proinflammatory cytokines and the histopathological profile, and reduced fungal burden. Therefore, the present study shows a new role for P. brasiliensis EVs in the presence of adjuvant as modulators of the host immune system, suggesting their utility as immunizing agents.