Potential Probiotic Lactic Acid Bacteria with Anti-Penicillium expansum Activity from Different Species of Tunisian Edible Snails.

This study aimed to isolate lactic acid bacteria (LAB) from the digestive tract, meat and slime of edible snails (Helix lucorum, Helix aspersa and Eobania vermiculata) and investigate their antagonistic activity against Penicillium expansum. They were then characterized for their probiotic potential. Among 900 bacterial isolates, 47 LAB exhibiting anti-P. expansum activity were identified through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as Levilactobacillus brevis (25), Lactococcus lactis (3), Enterococcus faecium (12), Enterococcus faecalis (4), Enterococcus casseliflavus (1), and Enterococcus mundtii (2). Sixty-two percent of the strains were tolerant to 100 mg/L of lysozyme. Seventy two percent of the isolates were able to survive at pH 3 and most of them tolerate 2.5% bile salt concentration. Moreover, 23% of the strains displayed bile salt hydrolase activity. Interestingly, all strains were biofilm strong producers. However, their auto- and co-aggregation properties were time and pH dependent with high aggregative potentiality at pH 4.5 after 24 h. Remarkably, 48.94% of the strains showed high affinity to chloroform. The safety assessment revealed that the 47 LAB had no hemolytic activity and 64% of them lacked mucin degradation activity. All isolated strains were susceptible to gentamycin, streptomycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. Overall, 43 LAB strains showed inhibitory activity against a broad spectrum of pathogenic Gram-positive and gram-negative bacteria, fungi, and yeast. Our findings suggest that L. brevis (EVM12 and EVM14) and Ent. faecium HAS34 strains could be potential candidates for probiotics with interesting antibacterial and anti-P. expansum activities.

Global forest management data for 2015 at a 100 m resolution.

Spatially explicit information on forest management at a global scale is critical for understanding the status of forests, for planning sustainable forest management and restoration, and conservation activities. Here, we produce the first reference data set and a prototype of a globally consistent forest management map with high spatial detail on the most prevalent forest management classes such as intact forests, managed forests with natural regeneration, planted forests, plantation forest (rotation up to 15 years), oil palm plantations, and agroforestry. We developed the reference dataset of 226 K unique locations through a series of expert and crowdsourcing campaigns using Geo-Wiki ( https://www.geo-wiki.org/ ). We then combined the reference samples with time series from PROBA-V satellite imagery to create a global wall-to-wall map of forest management at a 100 m resolution for the year 2015, with forest management class accuracies ranging from 58% to 80%. The reference data set and the map present the status of forest ecosystems and can be used for investigating the value of forests for species, ecosystems and their services.

Pancreas-Kidney Transplantation: Do We Know the Frequency of Clinical Complications?

BACKGROUND: The objective of this study was to describe the most common medical complications in simultaneous pancreas-kidney recipients in our center. METHODS: Retrospective and descriptive study of complications observed in a series of 73 simultaneous pancreas-kidney transplant recipients, which included 54 men and 19 women with an average age of 40.6 years, between February 2009 and April 2019. The study assessed the incidence of cytopenia, viral infections, tumors, and graft rejection. Frequency tables were created for each complication in the analysis. RESULTS: Cytopenia was the most common complication, either by itself or associated with a different complication, and it was found in 23.3% of all patients. The most common infection was cytomegalovirus, which was in 55.6% of all 9 patients who presented infections in spite of universal prophylaxis with valganciclovir, followed by herpes virus (11.1%), papillomavirus (11.1%), and polyoma BK virus (22.2%). Regarding tumors, the number of patients who presented this complication was low; 2 gynecologic tumors were detected (cervical intracellular neoplasia and one ovarian tumor), and 1 case of skin tumor was also observed. There were 3 cases of acute rejection, which represents 4.1% of all patients. Rejection was cellular and steroid-sensitive except for 1 case that was humoral, with good response to treatment. CONCLUSIONS: In spite of the doses of immunosuppressive drugs received by these patients, the incidence of infections was low, and cytomegalovirus was the most common infection. As a consequence of the drugs administered, virtually all patients developed cytopenia. The number of tumors observed in this series was low in spite of the immunosuppressive treatment.

A Simple, Affordable, Rapid, Stabilized, Colorimetric, Versatile RT-LAMP Assay to Detect SARS-CoV-2.

The SARS-CoV-2 pandemic has forced all countries worldwide to rapidly develop and implement widespread testing to control and manage the Coronavirus Disease 2019 (COVID-19). reverse-transcription (RT)-qPCR is the gold standard molecular diagnostic method for COVID-19, mostly in automated testing platforms. These systems are accurate and effective, but also costly, time-consuming, high-technological, infrastructure-dependent, and currently suffer from commercial reagent supply shortages. The reverse-transcription loop-mediated isothermal amplification (RT-LAMP) can be used as an alternative testing method. Here, we present a novel versatile (real-time and colorimetric) RT-LAMP for the simple (one-step), affordable (~1.7 €/sample), and rapid detection of SARS-CoV-2 targeting both ORF1ab and N genes of the novel virus genome. We demonstrate the assay on RT-qPCR-positive clinical samples, obtaining most positive results under 25 min. In addition, a novel 30-min one-step drying protocol has been developed to stabilize the RT-LAMP reaction mixtures, allowing them to be stored at room temperature functionally for up to two months, as predicted by the Q10. This Dry-RT-LAMP methodology is suitable for potentially ready-to-use COVID-19 diagnosis. After further testing and validation, it could be easily applied both in developed and in low-income countries yielding rapid and reliable results.

LY-CoV1404 potently neutralizes SARS-CoV-2 variants

SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19. In BriefLY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated. HighlightsO_LILY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron), the BA.2 Omicron subvariant, and B.1.617.2 (Delta) variants C_LIO_LINo loss of potency against currently circulating variants C_LIO_LIBinding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID database C_LIO_LIBreadth of neutralizing activity and potency supports clinical development C_LI

Lymph Node Ratio, Perineural Invasion and R1 Resection as Independent Prognostic Factors in Pancreatic Adenocarcinoma: A Retrospective Cohort Study.

INTRODUCTION: The prognosis of pancreatic ductal adenocarcinoma has been associated with several factors. The aim of the present study was to correlate tumor-related factors and pathological findings with disease-free survival (DFS) and overall survival (OS) in patients undergoing pancreaticoduodenectomy. MATERIAL AND METHODS: From a prospectively maintained database, we reviewed 89 pancreatic ductal adenocarcinomas in patients who underwent pancreaticoduodenectomy from 2010 to 2014. The impact of histopathologic or tumor-related data, including a lymph node ratio greater than 15% (LNR15), on survival was analyzed. RESULTS: Univariate analysis of DFS and OS showed that vascular resection, pT, pN, LNR15, microvascular, lymphatic, and perineural invasion, and R1 resection influenced survival. Only LNR15, perineural invasion and R1 resection were independent predictors for both DFS (HR 6.39, p = 0.011; HR 8.53, p = 0.003; HR 9.68, p = 0.002, respectively) and OS (HR 4.21, p = 0.039; HR 5.41, p = 0.020; HR 4.41, p = 0.036, respectively). CONCLUSIONS: This study demonstrates that LNR15, perineural invasion and R1 resection are independently associated with DFS and OS.

Experimental Analysis of Interactions Among Saprotrophic Fungi from A Phosphorous-Poor Desert Oasis in the Chihuahuan Desert

Fungal ecological interactions play a key role in structuring community assemblages. These associations may involve both antagonistic and synergistic relationships, which are commonly influenced by abiotic factors such as nutrient conditions. However, information for extreme, oligotrophic systems remain poor. Herein, interactions among key members of the aquatic transient fungal community (Aspergillus niger, Cladosporium sp., and Coprinellus micaceus) of a low-nutrient freshwater system in the Cuatro Ciénegas Basin, Mexico were studied. Pairwise interaction bioassays were explored in vitro under different nutrient conditions, including carbohydrates-rich, carbohydrates and amino peptides-rich, and low nutrients. Our results indicated that antagonistic patterns prevail among the studied taxa. However, nutrient-dependent changes were observed in Cladosporium sp. shifting to synergy under carbohydrates-rich conditions, suggesting changes in the fungal community composition as a result of nutrient enrichment. Remarkably, our findings contrast with previous work demonstrating mainly synergistic interactions between our tested fungal isolates and co-occurring autochthonous bacteria (Aeromonas spp. and Vibrio sp.) under low-nutrient conditions. This observation may indicate that bacteria and fungi exhibit distinct community-level responses, driven by nutrient conditions. This contributes to the knowledge of fungal community dynamics and interspecific interactions in an oligotrophic ecosystem, highlighting the relevance of nutrient-based shifts and antagonistic interactions in ecosystem dynamics.

Macroscopic and microscopic evaluation of flapless alveolar perforations on experimental tooth movement

Abstract Objective: The aim of this study was to evaluate a flapless surgical technique as an alternative to traditional alveolar corticotomy used to accelerate orthodontic tooth movement (OTM). Methods: To induce OTM in Wistar rats, 40 cN of orthodontic force were applied to the maxillary left first molars. Forty rats were distributed into control groups (CG1, CG3, CG7 and CG14) and experimental groups (n= 5), in which alveolar perforations were made using a spear-shaped guide bur (EG1, EG3, EG7, EG14). Euthanasia dates were set at 1, 3, 7 and 14 days, respectively, after tooth movement began. The amount of OTM was measured with a caliper, and osteoclasts present in the periodontal ligament of the mesial root of the moved tooth were counted by means of histological evaluation (tartrate-resistant acid phosphatase staining, TRAP). Results: Although there was no difference in the amount of OTM within subgroups of corresponding experimental periods (p> 0.05), when EG14 and CG14 were compared, a larger number of osteoclasts was counted in the experimental group (p< 0.00). Conclusion: The authors concluded that flapless cortical alveolar perforations led to more intense osteoclastic activity on the fourteenth day; nevertheless, no evidence of accelerated OTM could be noted.

Resumo Objetivo: o objetivo do presente estudo foi avaliar a técnica cirúrgica sem retalho como alternativa à tradicional corticotomia alveolar utilizada para acelerar o movimento dentário experimental. Métodos: para induzir a movimentação dentária experimental em ratos Wistar, foram aplicados 40 cN de força ortodôntica aos primeiros molares superiores esquerdos. Quarenta ratos foram distribuídos nos grupos (n = 5) controles (GC1, GC3, GC7 e GC14) e experimentais (GE1, GE3, GE7, GE14), nos quais foram realizadas perfurações alveolares com uma ponta lança. As datas de eutanásia foram estabelecidas em 1, 3, 7 e 14 dias, respectivamente, após o início do movimento dentário. A quantidade de deslocamento dentário foi medida com um paquímetro e os osteoclastos presentes no ligamento periodontal da raiz mesial do dente movimentado foram contados por meio de avaliação histológica (coloração por fosfatase ácida resistente ao tartarato, TRAP). Resultados: embora não tenha havido diferença na quantidade de deslocamento dentário dentro dos subgrupos dos períodos experimentais correspondentes (p> 0,05), quando GC14 e GE14 foram comparados, um número maior de osteoclastos foi contado no grupo experimental (p< 0,00). Conclusão: os autores concluíram que as perfurações alveolares corticais sem retalho levaram a uma atividade osteoclástica mais intensa no décimo quarto dia; entretanto, nenhuma evidência de movimento dentário acelerado pôde ser notada.

Spatio-temporal tumor heterogeneity in metastatic CRC tumors: a mutational-based approach.

It is well known that activating mutations in the KRAS and NRAS genes are associated with poor response to anti-EGFR therapies in patients with metastatic colorectal cancer (mCRC). Approximately half of the patients with wild-type (WT) KRAS colorectal carcinoma do not respond to these therapies. This could be because the treatment decision is determined by the mutational profile of the primary tumor, regardless of the presence of small tumor subclones harboring RAS mutations in lymph nodes or liver metastases. We analyzed the mutational profile of the KRAS, NRAS, BRAF and PI3KCA genes using low-density microarray technology in samples of 26 paired primary tumors, 16 lymph nodes and 34 liver metastases from 26 untreated mCRC patients (n=76 samples). The most frequent mutations found in primary tumors were KRAS (15%) and PI3KCA (15%), followed by NRAS (8%) and BRAF (4%). The distribution of the mutations in the 16 lymph node metastases analyzed was as follows: 4 (25%) in KRAS gene, 3 (19%) in NRAS gene and 1 mutation each in PI3KCA and BRAF genes (6%). As expected, the most prevalent mutation in liver metastasis was in the KRAS gene (35%), followed by PI3KCA (9%) and BRAF (6%). Of the 26 cases studied, 15 (58%) displayed an overall concordance in the mutation status detected in the lymph node metastases and liver metastases compared with primary tumor, suggesting no clonal evolution. In contrast, the mutation profiles differed in the primary tumor and lymph node/metastases samples of the remaining 11 patients (48%), suggesting a spatial and temporal clonal evolution. We confirm the presence of different mutational profiles among primary tumors, lymph node metastases and liver metastases. Our results suggest the need to perform mutational analysis in all available tumor samples of patients before deciding to commence anti-EGFR treatment.

Management of cystic echinococcosis in the last two decades: what have we learned?

Background: Management options for cystic echinococcosis (CE) remain a serious problem. The main aim of this study was to examine the selection and complications of treatment applied in patients with CE. The second aim was to evaluate the mortality rate and causative factors. Methods: A retrospective descriptive study of patients diagnosed with CE between 1998 and 2015 was conducted, according to ICD-9 (code 122·0 to 122·9) criteria in the Complejo Asistencial Universitario of Salamanca, Spain. Results: Four-hundred-ninety-one (491) patients were diagnosed with CE disease and the treatment applied in these patients were: 166 (33.8%) patients received only surgery, 176 (35.8%) surgery and drugs, 17 (3.5%) drugs alone, in 131 (26.7%) patients the strategy was 'watch and wait', and only one patient (0.2%) was applied puncture-aspiration-injection-respiration (PAIR). Thus, a total of 342 patients received surgery, either alone (166) or combined with drugs (176), and a total of 193 (39.4%) patients were medically treated, either alone (17) or combined with surgery (176); 123 (63.7%) patients used albendazole alone; and 70 (36.3%) patients used a combination of albendazole and praziquantel. Sixty-five patients (19.0%) had complications after surgery and seven of them (2%) died. Only 15 (7.8%) cases had side effects from anthelmintics. Throughout the study period, 80 (16.3%) patients died, 14 (2.9%) of them due to CE disease. Conclusions: Complications of CE are one of the most common causes of mortality in CE patients, with size, location, and number of cysts, and the 'watch and wait' treatment strategy being the main factors associated with mortality.

Macroscopic and microscopic evaluation of flapless alveolar perforations on experimental tooth movement.

OBJECTIVE: The aim of this study was to evaluate a flapless surgical technique as an alternative to traditional alveolar corticotomy used to accelerate orthodontic tooth movement (OTM). METHODS: To induce OTM in Wistar rats, 40 cN of orthodontic force were applied to the maxillary left first molars. Forty rats were distributed into control groups (CG1, CG3, CG7 and CG14) and experimental groups (n= 5), in which alveolar perforations were made using a spear-shaped guide bur (EG1, EG3, EG7, EG14). Euthanasia dates were set at 1, 3, 7 and 14 days, respectively, after tooth movement began. The amount of OTM was measured with a caliper, and osteoclasts present in the periodontal ligament of the mesial root of the moved tooth were counted by means of histological evaluation (tartrate-resistant acid phosphatase staining, TRAP). RESULTS: Although there was no difference in the amount of OTM within subgroups of corresponding experimental periods (p> 0.05), when EG14 and CG14 were compared, a larger number of osteoclasts was counted in the experimental group (p< 0.00). CONCLUSION: The authors concluded that flapless cortical alveolar perforations led to more intense osteoclastic activity on the fourteenth day; nevertheless, no evidence of accelerated OTM could be noted.

Therapeutic Effects of Resiniferatoxin Related with Immunological Responses for Intestinal Inflammation in Trichinellosis

The immune response against Trichinella spiralis at the intestinal level depends on the CD4⁺ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, INF-γ, IL-1β, TNF-α, NO, and PGE₂, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

Imported cystic echinococcosis in western Spain: a retrospective study.

BACKGROUND: In Spain, 12% of the population are immigrants. The impact of immigration in Spain on cystic echinococcosis (CE) is unknown. The aim of this study was to describe the epidemiology of CE in immigrants in western Spain. METHODS: First, a retrospective descriptive study of patients diagnosed with CE in the University Hospital of Salamanca (CAUSA) between January 1998 and December 2014 was designed. Second, we studied the seroprevalence of CE in sera from foreigners who received treatment in the Tropical Medicine Unit. RESULTS: A total of 550 patients with new CE-related diagnoses were registered; of these, 16 (2.9%) were immigrants, of whom 10 (63%) were male. The age (mean±SD) was 34.6±12.8 years. The incidence rate of CE in immigrants was 8.76 cases per 105 person-years. Eight (50%) cases presented asymptomatically. Seroprevalence of CE in foreign patients was 2.3%. It was higher in North African population (4.2%), followed by sub-Saharan (2.4%) and Latin American (1.8%) (p=0.592) populations. The seroprevalence was higher in those who arrived recently (<12 months) vs those who arrived earlier (≥12 months), 3.5% vs 1.3% (p=0.077). CONCLUSIONS: The epidemiological and clinical characteristics of CE in immigrants are different than those of the native population, and their influence on CE burden in our endemic area is still limited.

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

Prevalence of Congenital Heart Disease and Pulmonary Hypertension in Down's Syndrome: An Echocardiographic Study

BACKGROUND: Down's syndrome (DS) is a genetic anomaly, which undergoes increased morbidity and mortality when associated with congenital heart disease (CHD). The aims of the study were to determine the prevalence of CHD and pulmonary hypertension (PH) in DS. METHODS: One hundred twenty-seven patients with DS living in Mexico City were evaluated by physical exam, electrocardiogram and echocardiogram. RESULTS: CHD was found in 40%. In 80% (n = 102) PH was present [systolic pulmonary artery pressure (SPAP) of 47 +/- 19 mm Hg and mean pulmonary artery pressure (MPAP) of 32 +/- 11 mm Hg]. Patients with CHD and PH were classified as having 1) no shunt (n = 18) with SPAP of 37 +/- 9 mm Hg and MPAP of 25 +/- 6 mm Hg and 2) with shunt (n = 26) with PASP of 57 +/- 29 mm Hg and MPAP of 38 +/- 19 mm Hg (p < or = 0.001). In those without CHD or with CHD without shunt (n = 76), SPAP was 37 +/- 19 mm Hg and the MPAP 25 +/- 6 mm Hg. The prevalence of PH in DS was 5.9% at one year and 15% at 10 years. The odds ratio of PH in DS with CHD was 7.3 vs. 3 without CHD. CONCLUSION: DS has a high prevalence of CHD and PH. PH prevalence increases when it is associated with CHD. The pathophysiology of PH in DS without CHD should be studied in the near future. Echocardiography is an indispensible tool for evaluation of DS.

Relevance of eosinophilia and hyper-IgE in immigrant children.

Immigrants from undeveloped countries are a growing problem in Europe. Spain has become a frequent destination for immigrants (20% of whom are children) because of its geographic location and its historic and cultural links with Africa and Latin America. Eosinophilia is frequent in adult immigrants, travelers and expatriates coming from tropical areas. However, there are few studies that focus on the incidence and causes of tropical eosinophilia and hyper-IgE in immigrant children.We evaluated, prospectively, the prevalence and causes of eosinophilia and hyper-immunoglobulin E (IgE) in 362 immigrant children coming from Sub-Saharan Africa, Northern Africa and Latin America to Salamanca, Spain, between January 2007 and December 2011.Absolute eosinophilia and hyper-IgE were present in 22.9% and 56.8% of the analyzed children, respectively. The most frequent causes of absolute eosinophilia were filariasis (52.6%), strongyloidiasis (46.8%) and schistosomiasis (28.9%). Filariasis (41.9%), strongyloidiasis (29.6%) and schistosomiasis (22.2%) were the most frequent causes of increased levels of IgE. The area under the ROC curve showed similar values between eosinophil count and IgE levels in the diagnosis of helminthiasis (69% [95% confidence interval (CI) 63%-74%] vs 67% [95% CI 60%-72%], P = 0.24). Eosinophilia and hyper-IgE have a high value as biomarkers of helminthiasis in children coming from tropical and subtropical areas.

Toll-like 4 receptor inhibitor TAK-242 decreases neuroinflammation in rat brain frontal cortex after stress.

BACKGROUND: The innate immune response is the first line of defence against invading microorganisms and it is also activated in different neurologic/neurodegenerative pathological scenarios. As a result, the family of the innate immune toll-like receptors (TLRs) and, in particular, the genetic/pharmacological manipulation of the TLR-4 signalling pathway emerges as a potential therapeutic strategy. Growing evidence relates stress exposure with altered immune responses, but the precise role of TLR-4 remains partly unknown. METHODS: The present study aimed to elucidate whether the elements of the TLR-4 signalling pathway are activated after acute stress exposure in rat brain frontal cortex and its role in the regulation of the stress-induced neuroinflammatory response, by means of its pharmacological modulation with the intravenous administration of the TLR-4 specific inhibitor TAK-242. Considering that TLR-4 responds predominantly to lipopolysaccharide from gram-negative bacteria, we checked whether increased intestinal permeability and a resultant bacterial translocation is a potential regulatory mechanism of stress-induced TLR-4 activation. RESULTS: Acute restraint stress exposure upregulates TLR-4 expression both at the mRNA and protein level. Stress-induced TLR-4 upregulation is prevented by the protocol of antibiotic intestinal decontamination made to reduce indigenous gastrointestinal microflora, suggesting a role for bacterial translocation on TLR-4 signalling pathway activation. TAK-242 pre-stress administration prevents the accumulation of potentially deleterious inflammatory and oxidative/nitrosative mediators in the brain frontal cortex of rats. CONCLUSIONS: The use of TAK-242 or other TLR-4 signalling pathway inhibitory compounds could be considered as a potential therapeutic adjuvant strategy to constrain the inflammatory process taking place after stress exposure and in stress-related neuropsychiatric diseases.