Increased neutrophil derived chemokines (CXCL10 and CCL2) in human trichinellosis as possible serological markers of the polarization of the immune response against the parasite.

Trichinella britovi is a widely distributed parasitic nematode, transmitted through ingestion of raw or poorly cooked meat containing muscle larvae. This helminth can regulate the host immune system during the early phase of infection. The immune mechanism mainly involves the interaction of Th1 and Th2 responses and related cytokines. Chemokines (C-X-C or C-C) and matrix metalloproteinases (MMPs) have also shown to be implicated in a number of parasitic infections, mainly malaria, neurocysticercosis, angiostronyloidosis, and schistosomiasis, but poor is known about their role in human Trichinella infection. We previously found that serum MMP-9 levels were significantly increased in T. britovi infected patients with relevant symptoms such as diarrhea, myalgia, and facial oedema, which makes these enzymes a potential reliable indicator of inflammation in trichinellosis patients. These changes were also observed in T. spiralis/T. pseudospiralis experimentally infected mice. No data are available about circulating levels of two pro-inflammatory chemokines, CXCL10 and CCL2, in trichinellosis patients with or w/o clinical signs of the infection. In this study, the association of serum level of CXCL10 and CCL2 with clinical outcome of T. britovi infection and their relation to MMP-9 were investigated. Patients (median age 49 ± 0.33 years) acquired infection by consuming raw sausages prepared with wild boar and pork meat. Sera were collected during the acute and the convalescent phases of the infection. A positive significant association (r = 0.61, p = 0.0004) was observed between MMP-9 and CXCL10 levels. The CXCL10 level significantly correlated with the severity of symptoms in patients being particularly higher in patients suffering diarrhea, myalgia, and facial oedema, thus suggesting a positive association of this chemokine with symptomatologic traits, especially myalgia (and increased LDH and CPK levels) (p < 0.005). No correlation was found between levels of CCL2 and the clinical symptoms.

Inhalation of dimethyl fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mice.

RATIONALE: The FDA-approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis (MS) treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. OBJECTIVE: Investigated the potential effects of solid lipid nanoparticles (SLNs) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: EAE was induced using MOG35-55 peptide in female C57BL/6J mice and the mice were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 h during 21 days. RESULTS: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared with EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-α and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. CONCLUSION: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

Trichinella spiralis excretory-secretory products downregulate MMP-9 in Dark Agouti rats affected by experimental autoimmune encephalomyelitis.

Matrix metalloproteinases (MMPs), are implicated in the pathogenesis of multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). Our aim was to investigate whether amelioration of EAE in Dark Agouti (DA) rats, induced by Trichinella spiralis muscle larvae excretory-secretory products (ES L1), could be related to the level and activity of gelatinases, MMP-9 and MMP-2. Serum levels of MMP-9, MMP-2, NGAL/MMP-9, TIMP-1, and cytokines, evaluated by gel-zymography or ELISA, as well as gelatinases and TIMP-1 expression in the spinal cord (SC), were determined in: i) EAE induced, ii) ES L1-treated EAE induced animals. Milder clinical signs in ES L1-treated EAE induced DA rats were accompanied with lower serum levels of MMP-9 and NGAL/MMP-9 complex. However, the correlation between the severity of EAE and the level of serum MMP-9 was found only in the peak of the disease, with MMP-9/TIMP-1 ratio higher in EAE animals without ES L1 treatment. Lower expression of MMP-9 in SC of ES L1-treated, EAE induced rats, correlated with the reduced number of SC infiltrating cells. In SC infiltrates, in the effector and the recovery phase, production of anti-inflammatory cytokines IL-4 and IL-10 was higher in animals treated with ES L1 prior to EAE induction, compared to untreated EAE animals. Reduced expression of MMP-9 in SC tissue, which correlated with the reduced number of infiltrating cells, might be ascribed to regulatory mechanisms, among which is IL-10.

Effects of Azadirachta indica seed kernel extracts on early erythrocytic schizogony of Plasmodium berghei and pro-inflammatory response in inbred mice.

BACKGROUND: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria. METHODS: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively. RESULTS: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test. In this treatment group, MMP-9 and TNF levels were notably higher than those measured in the same mouse strain treated with the anti-malarial drug artesunate, Azadirachta indica kernel extracts from ripe fruits or solvent. In BALB/c mice, treatment with kernel extracts did not influence parasitaemia. MMP-9 and TNF levels measured in this mouse strain were notably lower than those recorded in C57BL/6 mice and did not vary among treatment groups. CONCLUSIONS: The effects of the ME on the parasite-host interactions appeared to be mouse strain-dependent, but also related to the ripening stage of the neem fruits, as only the unripe fruit seed kernel extracts displayed appreciable bioactivity.

Bipolar Disorder With Psychotic Features and Ocular Toxoplasmosis: A Possible Pathogenetic Role of the Parasite?

Recent evidence suggests the involvement of Toxoplasma gondii infection in the emergence of psychotic and affective disorders. In this report, we describe the case of a young Brazilian woman affected by recurrent ocular toxoplasmosis and presenting with a manic episode with psychotic features in the context of a diagnosis of Bipolar Disorder (BD), type I. We observed a relationship between ocular manifestations and the clinical course of bipolar illness, confirmed by molecular analyses (nested-PCR), as well as by the high level of T. gondii specific IgG. This case report is the first showing the presence of circulating parasite DNA at the time of occurrence of psychiatric symptoms, thus providing further support for a possible role of the parasite in the pathogenesis of some cases of BD.

180° turn while walking: characterization and comparisons between subjects with and without stroke.

[Purpose] Limitations in performing the 180°-turning increase the risk of falls and disabilities in stroke patients. The aim of this study was to characterize and compare the 180°-turning between people with and without stroke, considering the direction towards which they turned. [Subjects and Methods] Fourteen subjects with stroke and 14 matched healthy controls performed the 180°-turning twice while walking: towards the self-selected, and the opposite directions. The turning performances were recorded using three video cameras. The videos were randomly analyzed by a single examiner, who characterized the turning, while considering the time required to complete the task, the number of steps, balance, and turning type. Friedman Tests and ANOVA (2 × 2) were used to compare the groups and turning direction factors (turning towards the self-selected versus opposite sides, and towards the paretic/non-dominant versus non-paretic/dominant sides). [Results] No interaction between the groups and turning directions, and no significant differences between the turning directions were found. However, significant differences were found between the groups for all variables used to characterize the turning performance, except for the type of turning. [Conclusion] Stroke subjects demonstrated poor performance on the 180°-turning, regardless of the turning direction. Duration, number of steps, and balance loss indicated difficulties in turn performance.

Evaluation of psychosomatic distress and its influence in the outcomes of lumbar fusion procedures for degenerative disorders of the spine.

The authors aim to evaluate the ability of spine surgeons to subjectively identify patients with psychological distress in a subset of lumbar fusion candidates, and the influence of such factors on surgical outcomes. From a cohort of 85 patients who had received a surgical indication for lumbar fusion and were subjectively evaluated for psychological distress, 60 were included in the study and underwent objective evaluation using the Distress Risk Assessment Method (DRAM) evaluation for depressive/distress symptoms, VAS and Oswestry scores pre- and postoperatively. Fifty-six patients were available with a minimum 6-month follow-up: 20 presented with normal DRAM scores, and 36 with abnormal DRAM (28 at risk; 4 distressed somatic; 4 distressed depressive). Although the group improved significantly with surgery regarding VAS and Oswestry, it was not the case for the DRAM score. The abnormal DRAM group had inferior VAS, Oswestry and satisfaction rates in comparison with the normal DRAM group. A significant number of patients in the at-risk group reduced their DRAM scores and were classified as normal patients at the end of the study. This study emphasizes the need for objective psychological screening on chronic low back pain patients and that although patients with abnormal DRAM scores benefit from surgery, they report inferior outcomes and satisfaction in comparison with the normal DRAM group.

Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing.

Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting KSP and AurB selectively affect dividing cells and have shown significant activity in vitro. However, these drugs, despite advancing to clinical trials, often yield unsatisfactory outcomes as monotherapy, likely due to variable responses driven by cyclin B degradation and apoptosis signal accumulation networks. Accumulated data suggest that combining emerging antimitotics with various cytostatic drugs can enhance tumor-killing effects compared to monotherapy. Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. The combination of BH3-mimetics with both KSP and AurB inhibitors synergistically induced substantial cell death, primarily through apoptosis. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness.

Cannabidiol Attenuates In Vivo Leukocyte Recruitment to the Spinal Cord Microvasculature at Peak Disease of Experimental Autoimmune Encephalomyelitis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation leading to demyelination. The associated symptoms lead to a devastating decrease in quality of life. The cannabinoids and their derivatives have emerged as an encouraging alternative due to their management of symptom in MS. Objective: The aim of the study was to investigate the mechanism of action of cannabidiol (CBD), a nonpsychoactive cannabinoid, on molecular and cellular events associated with leukocyte recruitment induced by experimental autoimmune encephalomyelitis (EAE). Materials and Methods: C57BL/6 female mice were randomly assigned to the four experimental groups: C (control group), CBD (cannabidiol-treated group, 5 mg/kg i.p.; 14 days), EAE (experimental autoimmune encephalomyelitis-induced group), and EAE+CBD (experimental autoimmune encephalomyelitis-induced plus cannabidiol-treated group). Results: The results indicated that 5 mg/kg of CBD injected intraperitoneally between the 1st and 14th days of EAE could reduce the leukocyte rolling and adhesion into the spinal cord microvasculature as well cellular tissue infiltration. These results were supported by a decreased mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the spinal cord. Conclusion: Purified CBD reduces in vivo VCAM and ICAM-mediated leukocyte recruitment to the spinal cord microvasculature at EAE peak disease.

Toxoplasmosis and neuropsychiatric diseases: can serological studies establish a clear relationship?

Toxoplasmosis is a widespread infection, with clinical spectrum ranging from a completely asymptomatic infection to multi-organ involvement. After entering the body, the parasite forms tissue cysts and establishes a chronic infection, involving also the central nervous system (CNS). During the last years, a lot of research has focused on the possible link between exposure to T. gondii and development of neuropsychiatric disorders such as schizophrenia and Parkinson's disease (PD). If a firm association between Toxoplasma infection and neuropsychiatric disorders will be established, this would lead to novel strategies for their prevention and treatment. We will review data from serological and neurodevelopment studies relating infection with T. gondii to such neuropsychiatric diseases.

The effect of nonylphenol on the motility and viability of bovine spermatozoa in vitro.

The objective of this in vitro study was to determine the effect of nonylphenol (NP) as an environmental toxicant on the spermatozoa motility and viability. The dose- and time-dependent effect of nonylphenol (1, 10, 100 and 200 µg/mL) dissolved either in 0.1% dimethyl sulfoxide (DMSO) or 0.1% ethanol (ETOH) on the motility and viability of bovine spermatozoa, as a cell model, during several time periods (0 h, 2 h, 4 h and 6 h) were examined. The motility of spermatozoa was determined by the Sperm Vision(TM) CASA (Computer Assisted Semen Analyzer) system. The results showed decreased spermatozoa motility in all experimental groups with the addition of NP dissolved in 0.1% DMSO and 0.1% ETOH (P < 0.001 and P < 0.05). The lowest spermatozoa motility was found at doses > 100 µg/mL of NP in comparison with the control group. The viability of bovine spermatozoa detected by the MTT cytotoxicity assay was decreased significantly (P < 0.001) in all experimental groups with NP dissolved in 0.1% ETOH. The viability in groups with NP dissolved in 0.1% DMSO was significantly (P < 0.05) decreased at 1 µg/mL of NP and significantly decreased (P < 0.001) at doses > 10 µg/mL of NP. After 6 h of culture the MTT assay proved a negative effect of all NP doses the on cell viability. The obtained data clearly indicate the negative effect of NP as an endocrine disruptor on spermatozoa motility and viability, which should be seriously considered in the case of exposure to NP in animals and humans and as a reason of male reproductive dysfunction.

Combination Therapy as a Promising Way to Fight Oral Cancer.

Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has become the standard practice for the treatment of locally advanced oral cancer, emerging as an effective approach in improving outcomes. In this review, we present an in-depth analysis of the current advancements in combination therapies for oral cancer. The review explores the current therapeutic options and highlights the limitations of monotherapy approaches. It then focuses on combinatorial approaches that target microtubules, as well as various signaling pathway components implicated in oral cancer progression, namely, DNA repair players, the epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, and immune checkpoint proteins. The review discusses the rationale behind combining different agents and examines the preclinical and clinical evidence supporting the effectiveness of these combinations, emphasizing their ability to enhance treatment response and overcome drug resistance. Challenges and limitations associated with combination therapy are discussed, including potential toxicity and the need for personalized treatment approaches. A future perspective is also provided to highlight the existing challenges and possible resolutions toward the clinical translation of current oral cancer therapies.

Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction.

Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks. We investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic navitoclax in lung cancer cells treated with the selective CENPE inhibitor GSK923295 (mitotic blocker) or the MPS1 inhibitor BAY1217389 (mitotic driver). Our aim was to steer treated cancer cells towards cell death. BH3-mimetics, in combination with both mitotic blockers and drivers, induced substantial cell death, mainly through apoptosis, in 2D and 3D cultures. Crucially, these synergistic concentrations were less toxic to non-tumor cells. This highlights the significance of combining BH3-mimetics with antimitotics, either blockers or drivers, which have reached the clinical trial phase, to enhance their effectiveness.

Comparison Between Surgical and Conservative Treatment for AOSpine Type A3 and A4 Thoracolumbar Fractures without Neurological Deficit: Prospective Observational Cohort Study.

Objective To compare the clinical results between conservative (CS) and surgical treatment (CXS) of A3 and A4 fractures without neurological deficit. Methods Prospective observational study of patients with thoracolumbar fractures type A3 and A4. These patients were separated between the surgical and conservative groups, and evaluated sequentially through the numeric rating scale (NRS), Roland-Morris disability questionnaire (RMDQ), EuroQol-5D (EQ-5D) quality of life questionnaire, and Denis work scale (DWS) up to 2.5 years of follow-up. Results Both groups showed significant improvement, with no statistical difference in pain questionnaires (NRS: CXS 2.4 ± 2.6; CS 3.5 ± 2.6; p > 0.05), functionality (RMDQ: CS 7 ± 6.4; CXS 5.5 ± 5.2; p > 0.05), quality of life (EQ-5D), and return to work (DWS). Conclusion Both treatments are viable options with equivalent clinical results. There is a tendency toward better results in the surgical treatment of A4 fractures.

Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems.

The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies should accelerate cell death in mitosis before slippage. Here, we undertook a mechanistic analysis to test whether the apoptosis activator Navitoclax potentiates apoptosis triggered by the antimitotic BI2536, a potent inhibitor of Polo-like kinase 1 (PLK1) with the goal of overcoming slippage. We found that cancer cells in 2D cultures treated with BI2536 alone accumulate in mitosis, but a significant fraction of arrested cells undergo slippage and survive. Remarkably, combining BI2536 with Navitoclax dramatically reduces slippage, shifting the cell fate to accelerated death in mitosis. The results are confirmed in 3D spheroids, a preclinical system that mimics in vivo tumor drug responses. Importantly, in 3D spheroids, the effect of the BI2536/Navitoclax combination requires a lower therapeutic dosage of each drug, underlying its potential to improve the therapeutic index. Our results highlight the relevance of apoptosis potentiators to circumvent slippage associated with antimitotics. The combination of BI2536 with Navitoclax shows in vitro synergy/additive effect, which warrants further clinical research.

Glutathione-S-transferase omega 1 and nurse cell formation during experimental Trichinella infection.

The glutathione-S-transferases omega (GSTO) are multifunctional enzymes involved in cellular defense. During the nurse cell (NC) formation in Trichinella spiralis infection, the structural and regulatory genes of the skeletal muscle cell are downregulated and a new phenotype is acquired which advances parasite growth and survival. Previous studies showed that the GSTO1 is overexpressed in the NC during T. spiralis infection. To clarify the role of GSTO1 during NC formation, we evaluated the production of this enzyme by immunohistochemistry (IHC) in the diaphragms of mice experimentally infected with T. spiralis at 15, 28 and 60 days post infection (dpi); phosphorylation of Akt (p-Akt) and JNK1 (p-JNK1) were also evaluated. Furthermore, we evaluated the in vitro effects of T. spiralis excretory/secretory (ES) products from muscle larvae on specific functions (viability, proliferative response, apoptosis) in two cell lines (HeLa and U937), as well as its ability to induce GSTO1, p-AkT, p-ERK1/2 and p-JNK1. Results showed that GSTO1 was elevated in NC present in the diaphragms of T. spiralis experimentally infected mice at 15 dpi and progressively increased up to 60 dpi. The activation pattern of Akt in NC was similar to that of GSTO1, whereas JNK1 was never phosphorylated. ES induced a dose-dependent proliferative response in U937 cells, at 24 h and 48 h of treatment, but not in HeLa cells. However, after 72 h following treatment, significant cell death was observed in both cell lines at all doses. The apoptotic index (a.i.) was significantly higher than in untreated cells in both cell lines but only at the highest concentration of ES tested. Furthermore, Western Blots revealed that cells treated with ES for 24, 48 and 72 h, exhibited time-dependent overexpression of GSTO1, whereas p-Akt appeared only after 24 h of treatment. The p-ERK-1/2 peaked at 24 h then declined at 48 h and 72 h after treatment; however, it remained significantly higher than in untreated cells. No changes were observed in p-JNK1 at 24 and 48 h after treatment but a sharp increase in p-JNK1 was observed at 72 h. Also in HeLa cells, ES induced a small but significant increase in GSTO1 expression after 24 and 48 h of treatment where p-JNK1 was present only after 72 h of treatment. In conclusion, T. spiralis ES can reproduce in vitro the modifications observed inside the NC during experimental infection in mice.

Adhesive systems applied to dentin substrate under electric current: systematic review.

OBJECTIVES: The purpose of this systematic review was to collect and discuss the technique of adhesive systems application on dentin substrate under electric current. MATERIALS AND METHODS: The first search strategy was based on data available at PubMed, LILACS, Scielo, Scopus, and Cochrane Library, using a combination of descriptors such as "dentin bond agents OR adhesive system AND electric current OR electrobond" or "dentin bonding agents OR dentin bonding agent application OR adhesive system AND electric current OR electrobond", with no limit regarding the publication year. The second search strategy was based on the articles' references found previously. An additional search strategy was applied that concerned the proposed theme in the SBU-UNICAMP (Unicamp's Library System Institutional Repository). RESULTS: Twelve studies published between 2006 and 2020 were found. The analyses of the selected studies showed that the use of electric current during adhesive systems application on dentin, whether conventional or self-conditioning, increases resinous monomer infiltration in the dentin substrate, which improves the hybridization processes and the bond strength of the restorative material to dentin. CONCLUSIONS: Despite the favorable results related to the use of this technique, there is still no specific protocol for the application of adhesive systems under electric current.

LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model.

Cationic anticancer peptides have exhibited potent anti-proliferative and anti-inflammatory effects in neoplastic illness conditions. LyeTx I-b is a synthetic peptide derived from Lycosa erythrognatha spider venom that previously showed antibiotic activity in vitro and in vivo. This study focused on the effects of LyeTxI-b on a 4T1 mouse mammary carcinoma model. Mice with a palpable tumor in the left flank were subcutaneously or intratumorally injected with LyeTx I-b (5 mg/kg), which significantly decreased the tumor volume and metastatic nodules. Histological analyses showed a large necrotic area in treated primary tumors compared to the control. LyeTxI-b reduced tumor growth and lung metastasis in the 4T1 mouse mammary carcinoma model with no signs of toxicity in healthy or cancerous mice. The mechanism of action of LyeTx I-b on the 4T1 mouse mammary carcinoma model was evaluated in vitro and is associated with induction of apoptosis and cell proliferation inhibition. Furthermore, LyeTx I-b seems to be an efficient regulator of the 4T1 tumor microenvironment by modulating several cytokines, such as TGF-ß, TNF-α, IL-1ß, IL-6, and IL-10, in primary tumor and lung, spleen, and brain. LyeTx I-b also plays a role in leukocytes rolling and adhesion into spinal cord microcirculation and in the number of circulating leukocytes. These data suggest a potent antineoplastic efficacy ofLyeTx I-b.

Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research.

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell-cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.

Toxoplasma gondii Monitoring in Liver Transplantation Patients: A Single Center Cross-Sectional Study in an Italian Hospital.

Toxoplasma gondii (TG) is one of the most widespread intracellular parasites in the world, despite the slight declining trend in industrialized countries. Whilst the infection is often asymptomatic in immunocompetent hosts, in immunocompromised patients such as organ transplant recipients it can have important clinical sequels with even fatal consequences. We retrospectively reviewed 568 primary liver transplants (LT) from deceased donors from 2012 to 2017. Data were analyzed adjusting for year, gender, and age. The study objective was to assess the incidence of post-transplant TG infection and adherence to international guidelines for primary chemoprophylaxis. Prior to transplantation, 42.4% of recipients tested seronegative and 56.5% seropositive, while 36.6% of donors were seropositive and 40.4% showed undetermined serology. Anti-TG antibody titer was higher in patients born abroad (71.4%) versus Italy (54.8%). Among recipients at high risk of post-transplant TG infection, 82.7% of them received chemoprophylaxis, while in 17.3% of cases no prophylaxis was administered. At a mean (SD) follow-up of 21.2 (12.4) months no case of TG infection has been observed. Despite the low rate of adherence to recommendations, prophylaxis of high-risk LT recipients provides control of post-transplant TG infection risk. Review of current guidelines is warranted for low-risk populations.