Weight of evidence evaluation for chemical-induced immunotoxicity for PFOA and PFOS: findings from an independent panel of experts.

Immunotoxicity is the critical endpoint used by some regulatory agencies to establish toxicity values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, the hypothesis that exposure to certain per- and polyfluoroalkyl substances (PFAS) causes immune dysregulation is subject to much debate. An independent, international expert panel was engaged utilizing methods to reduce bias and "groupthink". The panel concluded there is moderate evidence that PFOS and PFOA are immunotoxic, based primarily on evidence from animal data. However, species concordance and human relevance cannot be well established due to data limitations. The panel recommended additional testing that includes longer-term exposures, evaluates both genders, includes other species of animals, tests lower dose levels, assesses more complete measures of immune responses, and elucidates the mechanism of action. Panel members agreed that the Faroe Islands cohort data should not be used as the primary basis for deriving PFAS risk assessment values. The panel agreed that vaccine antibody titer is not useful as a stand-alone metric for risk assessment. Instead, PFOA and PFOS toxicity values should rely on multiple high-quality studies, which are currently not available for immune suppression. The panel concluded that the available PFAS immune epidemiology studies suffer from weaknesses in study design that preclude their use, whereas available animal toxicity studies provide comprehensive dataset to derive points of departure (PODs) for non-immune endpoints. The panel recommends accounting for potential PFAS immunotoxicity by applying a database uncertainty factor to POD values derived from animal studies for other more robustly supported critical effects.

Repurposing Simvastatin in Parkinson's Disease Model: Protection Is throughout Modulation of the Neuro-Inflammatory Response in the Substantia nigra.

Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.

Taenia hydatigena larvae vesicular concentrates increase Anti-OVA IgG and the production of some cytokines in rats.

The effects of administration of four different fractions of T. hydatigena larvae vesicular concentrate (ThLVC) prior to immunization with ovalbumin (OVA) in rats on different parameters of the immune response were evaluated. The amount of anti-OVA IgG by ELISA, amount of blood eosinophils (BE), percentage of cell subpopulations by flow cytometry (CD3+/CD4+, CD3+/CD8+, CD3-/CD45RA+, and CD11b/c+), and production of serum cytokines by bead-based immunoassays (IL-2, IL-4, INFγ, IL-5, TNFα, GM-CSF, IL-17F, IL-17A IL-13, IL-22, and IL-6) were measured. Rats receiving total-ThLVC (p ≤ 0.05) and fraction ThLVC30-100 kDa (p < 0.001) prior to OVA administration produced higher amounts of anti-OVA IgG than rats receiving OVA alone. Rats that were only administered with OVA showed a strong increase in BE that was significantly correlated (r = 0.72, p < 0.001) with an increase in IL-5 in the blood. However, rats that received any of the ThLVC fractions prior to administration of OVA did not show these increases. In general, administration of ThLVC30-100 kDa prior to administration of OVA increased (p < 0.05) the percentage of B, CD4, and CD8 lymphocytes in the spleen and mesenteric lymph nodes. Rats that received ThLVC total fraction and OVA showed an increase (p < 0.05) in IL-2, IL17F, and IL22. The results of this study show that total-ThLVC and ThLVC30-100 kDa modify the immune response of rats in differentiated ways. Our observations suggests that both fractions of ThLVC have the potential to be used as adjuvants.

The Endocrine Disruptor Compound Bisphenol-A (BPA) Regulates the Intra-Tumoral Immune Microenvironment and Increases Lung Metastasis in an Experimental Model of Breast Cancer.

Breast cancer (BC) metastasis represents the main physiopathology leading to poor prognosis and death. Bisphenol A (BPA) is a pollutant, classified as an endocrine-disrupting chemical compound with estrogenic properties, their exposure in the early stages of neonatal life leads to an increase in the size and weight of breast tumors and induces cellular changes in the tumoral immune microenvironment where cytokines play a key role. Thus, we used female BALB/c mice exposed neonatally to a single dose of BPA. Once mice reached sexual maturity, a mammary tumor was induced, injecting 4T1 cells in situ. After 25 days of injection, we evaluated endocrine alterations, cytokine expression, tissue alterations denoted by macro or micro-metastasis in the lung, and cell infiltration induced by metastasis. We found that BPA neonatal treatment did not show significant endocrine alterations. Noteworthy, BPA led to an augmented rate of metastasis to the lung associated with higher intratumoral expression of IL-1ß, IL-6, IFN-γ, TNF-α, and VEGF. Our data suggest that cytokines are key players in the induction of BC metastasis and that BPA (an environmental pollutant) should be considered as a risk factor in the clinical history of patients as a possible inductor of BC metastasis.

Intratumoral Treatment with 5-Androstene-3ß, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer.

Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3ß, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 µM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.

Cysticidal effect of a pure naphthoquinone on Taenia crassiceps cysticerci.

Cysticercosis is a disease caused by the metacestode of the parasite Taenia solium (T. solium). In humans, the most severe complication of the disease is neurocysticercosis. The drug of choice to treat this disease is albendazole; however, the bioavailability and efficacy of the drug are variable. Therefore, new molecules with therapeutic effects against this and other parasitic infections caused by helminths must be developed. Naphthoquinones are naphthalene-derived compounds that possess antibacterial, antifungal, antitumoral, and antiparasitic properties. The aim of this work was to evaluate the in vitro anti-helminthic effect of 2-[(3-chlorophenylamino)phenylmethyl]-3-hydroxy-1,4-naphthoquinone, isolated from a natural source and then synthesized (naphthoquinone 4a), using an experimental model of murine cysticercosis caused by Taenia crassiceps (T. crassiceps). This compound causes paralysis in the cysticerci membrane from day 3 of the in vitro treatment. Additionally, it induces changes in the shape, size, and appearance of the cysticerci and a decrease in the reproduction rate. In conclusion, naphthoquinone 4a has in vitro cysticidal activity on T. crassiceps cysticerci depending on the duration of the treatment and the concentration of the compound. Therefore, it is a promising drug candidate to be used in T. crassiceps and possibly T. solium infections.

Bisphenol A induces protection through modulation of the immune response against the helminth parasite Taenia crassiceps.

AIMS: Industrial growth has increased the exposure to endocrine disruptor compounds (EDCs) in all organisms. Bisphenol A (BPA), an EDC, has been demonstrated to be involved in the susceptibility to parasite infections. However, few studies have analysed this connection in more depth. The aim of this study was to determine whether early BPA exposure in female mice affects the systemic immune response and the susceptibility to Taenia crassiceps infection. METHODS AND RESULTS: BALB/c mice were exposed to BPA at post-natal day 3. At 6 weeks of age, they were inoculated with T crassiceps larvae and, 2 weeks later, were euthanized. The number of parasites was quantified. By flow cytometry, in the spleen, the peripheral and mesenteric lymph nodes, the different innate and adaptive immune cell modulation was analysed, and RT-PCR cytokine expression was also evaluated. BPA induced a reduction of 40% in parasite load. BPA treatment modulated some lineages of the innate immune response and caused slight changes in cells belonging to the adaptive immune response. Additionally, BPA enhanced the type 2 cytokine profile. CONCLUSION: Neonatal BPA treatment in female mice affects not only the percentage of different immune cells but also their ex vivo cytokine gene expression, decreasing T crassiceps cysticercosis susceptibility.

The chemical environmental pollutants BPA and BPS induce alterations of the proteomic profile of different phenotypes of human breast cancer cells: A proposed interactome.

Breast cancer is one of the most common malignancies and the second leading cause of death in women. Despite efforts for its early detection, its worldwide incidence continues to increase. Thus, identification of risk factors for its development and new targets for its therapy are of vital importance. Environmental pollutants derived from human activity have been associated with predisposition to the development of cancer. Bisphenol A (BPA) is an endocrine disruptor compound (EDC) widely used in the manufacture of polycarbonates, and it has affinity for the estrogen receptor (ER). Scientific evidence has proposed an association between increased incidence of breast cancer and BPA exposure at lower doses. Among worldwide concerns with BPA exposure, different industries proceeded to replace BPA with analogs such as bisphenol S (BPS), which is now employed in products labelled as BPA-free. Nevertheless, recent studies exhibit that its exposure results in altered mammary gland development and morphogenesis; and promotes breast cancer cell proliferation. Of note, most of the effects of both BPA and BPS have been performed in estrogen-dependent breast cancer models. However, gaps in knowledge still exist on the roles and mechanisms that both compounds, specifically BPS, may play in cancer initiation and development in hormone-dependent and other types of breast cancer. Thus, the aim of the present study was to deepen the understanding of biological targets modulated by these ubiquitous pollutants in different breast cancer cell lines, representing two scenarios of this pathology: hormone-dependent and hormone-independent breast cancer. Results point out that both compounds induced proliferation in ER positive cells, not showing this effect in the ER-negative breast cancer cells. Different targets modified at the proteomic level in both breast cancer scenarios were also identified. Stem cell markers (eg. CD44) and invasion proteins (eg. MMP-14) were importantly increased by BPA and BPS in ER-positive breast cancer cells. In contrast, growth factors and associated receptors such as EGFR and TGF-ß were induced by BPS in the ER-negative breast cancer cells; both pollutants induced an increase of vascular endothelial growth factor (VEGF) protein secretion. This finding suggests that the use of BPS must be considered with more caution than BPA, since it can act independently of the presence of the hormonal receptor. These findings show new evidence that BPA and BPS exposure can contribute to breast cancer development and progression. Our results suggest that both BPA and BPS must be considered equally as outstanding risk factors for this pathology.

Perinatal exposure to bisphenol A increases in the adulthood of the offspring the susceptibility to the human parasite Toxocara canis.

Bisphenol A, a very widespread environmental pollutant and endocrine disruptor compound, can interact with several steroid receptors, particularly with estrogen ones. In different studies, it has observed that the endocrine disruption during critical periods of development can trigger alterations in the immune response during the adult life. Male Wistar rats were exposed indirectly to BPA at a dose of 250 µg/kg day during the perinatal period (from day 5 of pregnancy until day 21 postnatal), At the 60 days of age, the adulthood, animals were infected with larvated eggs of the Toxocara canis, and were sacrificed at 7 days post-infection. Parasitic loads in the lung and in the liver were analyzed by artificial digestion. Furthermore, immune cell subpopulations (macrophages, NK cells, Tγδ, total T cells, T helper, T cytotoxic, and B lymphocytes) present in spleen, peripheral and mesenteric lymph nodes were analyzed by flow cytometry. The expression of Th1 and Th2 cytokines at the splenic level was determined by real-time quantitative PCR. Finally, the titers of specific antibodies against to the parasite were analyzed by ELISA. The BPA treatment administrated in the perinatally stage favors a significant increase of the percentage of Toxocara canis larvae in the lungs and liver in the adulthood. Additionally, the exposure to this compound caused a dramatically decrease in the production of specific antibodies against to this parasite, downregulating together Th2 cytokines (IL-4, IL-5 and IL-13), meanwhile upregulated Th1 cytokines (IFN-γ and TNF-α). Perinatal exposure to BPA affects the performance of the immune response during adult life, modifying both cytokines and antibodies production by these cells, which favors the susceptibility to infections, specifically toxocariosis.

Immune response to chronic Toxocara canis infection in a mice model.

AIMS: The zoonotic nematode Toxocara canis causes larva migrans syndrome that induces an immune response characterized by the production of antibodies and eosinophilia. A Th2 polarization has been associated with the infection, but there are still details of the cellular and humoral immune response that need to be described. Thus, the aim of this study was to describe the systemic host immune response to T canis chronic infection in a mouse model. METHODS AND RESULTS: BALB/c mice were inoculated once with 500 T canis embryonated eggs, per os. After 49 days, the amounts of larval found in brain and muscle tissues were statistically two and four times higher, respectively, than the amounts found in lung, liver, kidney or heart tissues. Splenic proportions of F4/80+ cells, as well as B, cytotoxic T and CD4+ Foxp3+ lymphocytes, were statistically higher (P ≤ .05, P ≤ .01, P ≤ .001 and P ≤ .001, respectively) as compared with control mice. In lymph nodes, some of these proportions changed, with the exception of F4/80+ cells. IgG1 levels in infected mice sera were increased. IL-4, IL-10 and VEGF levels were statistically higher in spleen (P ≤ .05, all) and sera (P ≤ .01, P ≤ .05 and P ≤ .05, respectively) in the infected mice. Also, in infected animals, IL-5 serum levels were increased (P ≤ .01). CONCLUSION: These results suggest that T canis chronic infection in BALB/c mice results in a type 2 response with an incipient regulatory response.

Robotic surgery in public hospitals of Latin-America: a castle of sand?

INTRODUCTION: There is no information about the evolution of robotic programs in public hospitals of Latin-America. OBJECTIVE: To describe the current status and functioning of robotic programs in Latin-American public hospitals since their beginning to date. METHODS: We conducted a survey among leading urologists working at public hospitals of Latin-America who had acquired the Da Vinci laparoscopic-assisted robotic system. Questions included: date the program started, its utilization by other services, number and kind of surgeries, surgery paying system, surgery related deaths, occurrence and reasons of robotic program interruptions and its use for training purposes. Medians and 25-75 centiles (IQR) were estimated. RESULTS: Since 2009, there are ten public hospitals of four Latin-American countries that acquired the Da Vinci robotic system. The median number of months robotic programs has been functioning without considering transitory interruption: 43 (IQR 35, 55). Median number of urologic and total surgeries performed: 140 (IQR 94, 168) and 336 (IQR 292, 621), respectively. The corresponding median number of urologic and total surgeries performed per month: 3 (IQR 2, 5) and 8 (IQR 5, 11). Median number of total surgeries performed per year per institution was 94 (IQR 68,123). The median proportion of urologic cases was 40% (IQR 31, 48), ranging from 24 to 66%. Five of ten institutions had their urology programs transitory or definitively closed due to the high burden costs. CONCLUSION: Adoption and development of robotic surgery in some public hospitals of Latin-America have been hindered by high costs.

Sex-Associated Differential mRNA Expression of Cytokines and Its Regulation by Sex Steroids in Different Brain Regions in a Plasmodium berghei ANKA Model of Cerebral Malaria.

Cerebral malaria (CM) is the major complication associated with death in malaria patients, and its pathogenesis is associated with excessive proinflammatory cytokine production. Notably, the severity and mortality of natural infections with Plasmodium are higher in males than females, suggesting that sexual hormones influence both the pathogenesis of and immune response in CM. However, no studies on inflammation mediators in the brains of both sexes have been reported. In this work, the mRNA expression levels of the proinflammatory cytokines IL-1ß, IFN-γ, TNF-α, and IL-2 were measured in the preoptic area, hypothalamus, hippocampus, olfactory bulb, frontal cortex, and lateral cortex regions of gonadectomized female and male CBA/Ca mice infected with P. berghei ANKA (a recognized experimental CM model). Our findings demonstrate that both infection with P. berghei ANKA and gonadectomy trigger a cerebral sex dimorphic mRNA expression pattern of the cytokines IL-1ß, TNF-α, IFN-γ, and IL-2. This dimorphic cytokine pattern was different in each brain region analysed. In most cases, infected males exhibited higher mRNA expression levels than females, suggesting that sexual hormones differentially regulate the mRNA expression of proinflammatory cytokines in the brain and the potential use of gonadal steroids or their derivates in the immunomodulation of cerebral malaria.

Immunoregulatory Role of Cannabinoids during Infectious Disease.

Although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this drug increases susceptibility to infections because of the impact on the modulation of the immune system. Concerning the medicinal or recreational use of marijuana, its influence on the course of an infection, whether this has been caused by bacteria, viruses, parasites, and to a lesser degree, fungi, has been reported. Furthermore, there is evidence suggesting the involvement of the ECS in the control and elimination of infectious agents such as bacteria, viruses, and some protozoa; in the case of fungi, few studies are available so far. The purpose of this review is to present the existing studies related to infections and the ECS, the microbicidal effects of compounds isolated from Cannabis sativa, and the association between marijuana use and the development of rare pathologies in specific diseases.

In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii.

Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world's population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T. gondii. We examined the effects of the synthetic toxin cal14.1a (s-cal14.1a) from C. californicus on the tachyzoite form of T. gondii. Our results indicate that, at micromolar concentrations, s-cal14.1a lowers viability and inhibits host cell invasion (by 50% and 61%, respectively) on exposure to extracellular parasites. Further, intracellular replication decreased significantly while viability of the host cell was unaffected. Our study is the first report on the antiparasitic activity of a synthetic toxin of C. californicus.

A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6.

We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

The endocrine-immune network during taeniosis by Taenia solium: The role of the pituitary gland.

It is well known that sex hormones play an important role during Taenia solium infection; however, to our knowledge no studies exist concerning the immune response following complete or lobe-specific removal of the pituitary gland during T. solium infection. Thus, the aim of this work was to analyze in hamsters, the effects of lack of pituitary hormones on the duodenal immune response, and their impact on T. solium establishment and development. Thus, in order to achieve this goal, we perform anterior pituitary lobectomy (AL, n = 9), neurointermediate pituitary lobectomy (NIL, n = 9) and total hypophysectomy (HYPOX, n = 8), and related to the gut establishment and growth of T. solium, hematoxylin-eosin staining of duodenal tissue and immunofluorescence of duodenal cytokine expression and compared these results to the control intact (n = 8) and control infected group (n = 8). Our results indicate that 15 days post-infection, HYPOX reduces the number and size of intestinally recovered T. solium adults. Using semiquantitative immunofluorescent laser confocal microscopy, we observed that the mean intensity of duodenal IFN-γ and IL-12 Th1 cytokines was mildly expressed in the infected controls, in contrast with the high level of expression of these cytokines in the NIL infected hamsters. Likewise, the duodenum of HYPOX animals showed an increase in the expression of Th2 cytokines IL-5 and IL-6, when compared to control hamsters. Histological analysis of duodenal mucosa from HYPOX hamsters revealed an exacerbated inflammatory infiltrate located along the lamina propria and related to the presence of the parasite. We conclude that lobe-specific pituitary hormones affect differentially the T. solium development and the gut immune response.

Sex hormones modulate the immune response to Plasmodium berghei ANKA in CBA/Ca mice.

Susceptibility to malaria differs between females and males, and this sexual dimorphism may have important implications for the effects of vaccines and drugs. However, little is known about the mechanisms mediating these sexual differences. Because the main differences between sexes are dictated by sex hormones, we studied the effect of gonadal steroids on immune responses to malaria in CBA/Ca mice. We decreased sex hormones levels by gonadectomy and evaluated the splenic index and the cells involved in the immune response, including T cells (CD3(+), CD4(+), CD8(+) and NK(+)), B cells and macrophages (Mac-3(+)) in the spleens of female and male mice infected with Plasmodium berghei ANKA. In addition, we measured antibody and cytokine levels in blood. Gonadectomy increased T(+) and B(+) splenic cells in both sexes but increased Mac-3(+) cells only in male mice. By contrast, gonadectomy decreased the NK(+) cell population only in male mice. In general, female mice developed higher antibody levels than males. Contrary to our expectations, gonadectomy increased the synthesis of IgG1, IgG2b, IgG3, and total IgG in female mice, indicating negative regulation of antibody production by female sex hormones. Gonadectomy increased the synthesis of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) only in female mice, suggesting that female sex hormones have anti-inflammatory properties. This work demonstrates that the levels of sex hormones affect the immune response and should be considered when designing malaria vaccines.

Helminth infection alters mood and short-term memory as well as levels of neurotransmitters and cytokines in the mouse hippocampus.

UNLABELLED: Helminthic infections are important causes of morbidity and mortality in many developing countries, where children bear the greatest health burden. The ability of parasites to cause behavioral changes in the host has been observed in a variety of host-parasite systems, including the Taenia crassiceps-mouse model. In murine cysticercosis, mice exhibit a disruption in the sexual, aggressive and avoidance predator behaviors. OBJECTIVE: The present study was conducted to characterize short-term memory and depression-like behavior, as well as levels of neurotransmitters and cytokines in the hippocampus of cysticercotic male and female mice. METHODS: Cytokines were detected by RT-PCR and neurotransmitters were quantified by HPLC. RESULTS: Chronic cysticercosis infection induced a decrease in short-term memory in both male and female mice, having a more pronounced effect in females. Infected females showed a significant increase in forced swimming tests with a decrease in immobility. In contrast, male mice showed an increment in total activity and ambulation tests. Serotonin levels decreased by 30% in the hippocampus of infected females whereas noradrenaline levels significantly increased in infected males. The hippocampal expression of IL-4 increased in infected female mice, but decreased in infected male mice. CONCLUSION: Our study suggests that intraperitoneal chronic infection with cysticerci in mice leads to persistent deficits in tasks dependent on the animal's hippocampal function. Our findings are a first approach to elucidating the role of the neuroimmune network in controlling short-term memory and mood in T. crassiceps-infected mice.

Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies.

INTRODUCTION: Sexual dimorphism significantly influences cancer incidence and prognosis. Notably, females exhibit a lower risk and favorable prognosis for non-reproductive cancers compared to males, a pattern observable beyond the scope of risk behaviors such as alcohol consumption and smoking. Colorectal cancer, ranking third in global prevalence and second in mortality, disproportionately affects men. Sex steroid hormones, particularly estrogens and androgens, play crucial roles in cancer progression, considering epidemiological in vivo and in vitro, in general estrogens imparting a protective effect in females and androgens correlating with an increasing risk of colorectal cancer development. MAIN BODY: The hormonal impact on immune response is mediated by receptor interactions, resulting in heightened inflammation, modulation of NF-kB, and fostering an environment conducive to cancer progression and metastasis. These molecules also influence the enteric nervous system, that is a pivotal in neuromodulator release and intestinal neuron stimulation, also contributes to cancer development, as evidenced by nerve infiltration into tumors. Microbiota diversity further intersects with immune, hormonal, and neural mechanisms, influencing colorectal cancer dynamics. A comprehensive understanding of hormonal influences on colorectal cancer progression, coupled with the complex interplay between immune responses, microbiota diversity and neurotransmitter imbalances, underpins the development of more targeted and effective therapies. CONCLUSIONS: Estrogens mitigate colorectal cancer risk by modulating anti-tumor immune responses, enhancing microbial diversity, and curbing the pro-tumor actions of the sympathetic and enteric nervous systems. Conversely, androgens escalate tumor growth by dampening anti-tumor immune activity, reducing microbial diversity, and facilitating the release of tumor-promoting factors by the nervous system. These findings hold significant potential for the strategic purposing of drugs to fine-tune the extensive impacts of sex hormones within the tumor microenvironment, promising advancements in colorectal cancer therapies.