Lymphocyte B Subtypes in Peripheral Blood: A Prognostic Biomarker for COVID-19 Patients.

BACKGROUND: In view of the scientific gap in knowledge of the involvement of the B-cell compartment and clinical prognostic in SARS-CoV-2 infection, this work aims to evaluate the B-cell subsets and the presence of specific IgM and IgG, as well as neutralizing antibodies against SARS-CoV-2, in unvaccinated patients diagnosed with COVID-19. METHODS: This study included 133 patients with COVID-19. Cellular components were assessed by flow cytometry, and immunoglobulin levels and reactivity were measured by indirect enzyme-linked immunosorbent assay. RESULTS: Our results showed no changes in less differentiated B cells. However, non-switched memory B cells (NS-MBCs) and class-switched memory B cells (CS-MBCs) were reduced in the patients with moderate disease. Also, plasmablasts and double-negative (DN) or "atypical" memory B cells were increased in groups of patients with moderate to critical conditions. In addition, the production of IgM, IgG, and neutralizing antibodies against SARS-CoV-2 demonstrated a positive correlation between the positivity of antibodies against SARS-CoV-2 and disease severity. Besides being related to the development of a more severe course of the disease, the increase in DN B-cell count also contributed to a poorer disease outcome in patients with a higher percentage of these cells. On the other hand, we observed an increase in the absolute number of CS-MBCs in patients with greater chances of survival. CONCLUSIONS: This study demonstrates that the B-cell compartment may contribute to the development of clinical symptoms of COVID-19, with changes in B-cell subset counts linked to disease course and patient prognosis.

Ayahuasca-enhanced extinction of fear behaviour: Role of infralimbic cortex 5-HT2A and 5-HT1A receptors.

BACKGROUND AND PURPOSE: Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N-dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA-treated rats. EXPERIMENTAL APPROACH: We focused on the 5-HT1A and 5-HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis. KEY RESULTS: A single oral treatment with AYA containing 0.3 mg·kg-1 of DMT increased the within-session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT2A receptor antagonist MDL-11,939 and the 5-HT1A receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA. CONCLUSION AND IMPLICATIONS: Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress-related disorders.

T cell maturation is significantly affected by SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An adequate T cell response is essential not only for fighting disease but also for the creation of immune memory. Thus, the present study aims to evaluate the T cells of patients with moderate, severe and critical COVID-19 not only at the time of illness but also 2 months after diagnosis to observe whether changes in this compartment persist. In this study, 166 COVID-19 patients were stratified into moderate/severe and critical disease categories. The maturation and activation of T cells were evaluated through flow cytometry. In addition, Treg cells were analysed. Until 15 days after diagnosis, patients presented a reduction in absolute and relative T lymphocyte counts. After 2 months, in moderate/severe patients, the counts returned to a similar level as that of the control group. In convalescent patients who had a critical illness, absolute T lymphocyte values increased considerably. Patients with active disease did not show differentiation of T cells. Nonetheless, after 2 months, patients with critical COVID-19 showed a significant increase in CD4+ EMRA (CD45RA+ effector memory) T lymphocytes. Furthermore, COVID-19 patients showed delayed T cell activation and reduced CD8+ suppressor T cells even 2 months after diagnosis. A reduction in CD4+ Treg cells was also observed, and their numbers returned to a similar level as that of healthy controls in convalescent patients. The results demonstrate that COVID-19 patients have a delayed activation and differentiation of T cells. In addition, these patients have a great reduction of T cells with a suppressor phenotype.

Cannabidiol attenuates fear memory expression in female rats via hippocampal 5-HT1A but not CB1 or CB2 receptors.

Growing evidence from male rodent and human studies suggests that cannabidiol (CBD) modulates the expression of aversive memories and anxiety-related responses. The limited data on whether and how CBD influences these aspects in females could have therapeutic implications given the increased susceptibility of women to anxiety- and stress-related disorders relative to men. Female studies are also essential to examine inherent aspects that potentially contribute to differences in responsiveness to CBD. Here we addressed these questions in adult female rats. Contextually fear-conditioned animals acutely treated with CBD (1.0-10 mg/kg) were tested 45 min later. In subsequent experiments, we investigated the estrous cycle effects and the contribution of dorsal hippocampus (DH) serotonin 1A (5-HT1A) and cannabinoid types 1 (CB1) and 2 (CB2) receptors to CBD-induced effects on memory retrieval/expression. The effects of pre-retrieval systemic or intra-DH CBD administration on subsequent fear extinction were also assessed. Lastly, we evaluated the open arms avoidance and stretched-attend postures in females exposed to the elevated plus-maze after systemic CBD treatment. CBD 3.0 and 10 mg/kg administered before conditioned context exposure reduced females' freezing. This action remained unchanged across the estrous cycle and involved DH 5-HT1A receptors activation. Pre-retrieval CBD impaired memory reconsolidation and lowered fear during early extinction. CBD applied directly to the DH was sufficient to reproduce the effects of systemic CBD treatment. CBD 3.0 and 10 mg/kg reduced anxiety-related responses scored in the elevated plus-maze. Our findings demonstrate that CBD attenuates the behavioral manifestation of learned fear and anxiety in female rats.

Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction.

Women present increased susceptibility to anxiety- and stress-related disorders compared to men. A potentially promising pharmacological-based strategy to regulate abnormal aversive memories disrupts their reconsolidation stage after reactivation and destabilization. Male rodent findings indicate that cannabidiol (CBD), a relatively safe and effective treatment for several mental health conditions, can impair the reconsolidation of aversive memories. However, whether and how CBD influences it in females is still unknown. The present study addressed this question in contextually fear-conditioned female rats. We report that systemically administered CBD impaired their reconsolidation, reducing freezing expression for over a week. This action was restricted to a time when the reconsolidation presumably lasted (< six hours post-retrieval) and depended on memory reactivation/destabilization. Moreover, the impairing effects of CBD on memory reconsolidation relied on the activation of cannabinoid type-1 but not type-2 receptors located in the CA1 subregion of the dorsal hippocampus. CBD applied directly to this brain area was sufficient to reproduce the effects of systemic CBD treatment. Contextual fear memories attenuated by CBD did not show reinstatement, an extinction-related feature. By demonstrating that destabilized fear memories are sensitive to CBD and how it hinders mechanisms in the DH CA1 that may restabilize them in female rats, the present findings concur that reconsolidation blockers are viable and could be effective in disrupting abnormally persistent and distressing aversive memories such as those related to posttraumatic stress disorder.

Involvement of serotonergic neurotransmission in the antidepressant-like effect elicited by cholecalciferol in the chronic unpredictable stress model in mice.

Cholecalciferol deficiency has been associated with stress-related psychiatric disorders, particularly depression. Therefore, the present study investigated the antidepressant-like effect of cholecalciferol in female mice and the possible role of the serotonergic system in this response. The ability of cholecalciferol to elicit an antidepressant-like effect and to modulate serotonin levels in the hippocampus and prefrontal cortex of mice subjected to chronic unpredictable stress (CUS) was also investigated. The administration of cholecalciferol (2.5, 7.5, and 25 µg/kg, p.o.) for 7 days, similar to fluoxetine (10 mg/kg, p.o., serotonin reuptake inhibitor), reduced the immobility time in the tail suspension test, without altering the locomotor performance in the open-field test. Moreover, the administration of p-chlorophenylalanine methyl ester (PCPA - 100 mg/kg, i.p., for 4 days, a selective inhibitor of tryptophan hydroxylase, involved in the serotonin synthesis) abolished the antidepressant-like effect of cholecalciferol and fluoxetine in the tail suspension test, demonstrating the involvement of serotonergic system. Additionally, CUS protocol (21 days) induced depressive-like behavior in the tail suspension test and decreased serotonin levels in the prefrontal cortex and hippocampus of mice. Conversely, the administration of cholecalciferol and fluoxetine in the last 7 days of CUS protocol completely abolished the stress-induced depressive-like phenotype. Cholecalciferol was also effective to abrogate CUS-induced reduction on serotonin levels in the prefrontal cortex, but not in the hippocampus. Our results indicate that cholecalciferol has an antidepressant-like effect in mice by modulating the serotonergic system and support the assumption that cholecalciferol may have beneficial effects for the management of depression.

The relationship between peripheral immune response and disease severity in SARS-CoV-2-infected subjects: A cross-sectional study.

Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID-19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty-seven COVID-19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID-19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA-DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID-19 patients showed an increase in MPO, interleukin (IL)-12, IL-6, IL-10, and IL-8, accompanied by a reduction in IL-17A and NOx. IL-10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID-19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL-10 as a possible prognostic biomarker for COVID-19.

Antidepressant-like effect of guanosine involves activation of AMPA receptor and BDNF/TrkB signaling.

Guanosine is a purine nucleoside that has been shown to exhibit antidepressant effects, but the mechanisms underlying its effect are not well established. We investigated if the antidepressant-like effect induced by guanosine in the tail suspension test (TST) in mice involves the modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, voltage-dependent calcium channel (VDCC), and brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. We also evaluated if the antidepressant-like effect of guanosine is accompanied by an acute increase in hippocampal and prefrontocortical BDNF levels. Additionally, we investigated if the ability of guanosine to elicit a fast behavioral response in the novelty suppressed feeding (NSF) test is associated with morphological changes related to hippocampal synaptogenesis. The antidepressant-like effect of guanosine (0.05 mg/kg, p.o.) in the TST was prevented by DNQX (AMPA receptor antagonist), verapamil (VDCC blocker), K-252a (TrkBantagonist), or BDNF antibody. Increased P70S6K phosphorylation and higher synapsin I immunocontent in the hippocampus, but not in the prefrontal cortex, were observed 1 h after guanosine administration. Guanosine exerted an antidepressant-like effect 1, 6, and 24 h after its administration, an effect accompanied by increased hippocampal BDNF level. In the prefrontal cortex, BDNF level was increased only 1 h after guanosine treatment. Finally, guanosine was effective in the NSF test (after 1 h) but caused no alterations in dendritic spine density and remodeling in the ventral dentate gyrus (DG). Altogether, the results indicate that guanosine modulates targets known to be implicated in fast antidepressant behavioral responses (AMPA receptor, VDCC, and TrkB/BDNF pathway).

Barnyardgrass control using tank-mixed herbicides with saflufenacil and its influence in photosynthesis and chlorophyll fluorescence / Controle de capim-arroz mediante associações de herbicidas com saflufenacil e influência na fotossíntese e fluorescência de clorofila

The objectives of this research were to evaluate the interaction between herbicides mixed with saflufenacil for the control of barnyardgrass and to determine the effect on photosynthetic and chlorophyll fluorescence parameters. The experiment was conducted in a greenhouse in a 2x8 factorial scheme, whose factor A tested resistant and susceptible biotypes; and factor B the herbicides: saflufenacil (70 g a.i. ha-1), clomazone (180 g a.i. ha-1), imazapyr + imazapic (73.5 + 24.5 g a.i. ha-1), and cyhalofop (360 g a.i. ha-1), the mixtures of these herbicides with saflufenacil, and control without treatment. Weed control was assessed 7, 14, 21 and 28 days after herbicide application (DAA), as well as shoot dry matter at 28 DAA, photosynthetic parameters using infrared gas analyzer (IRGA), and emission of chlorophyll a fluorescence after 24 and 28 hours of application of treatments, respectively, and interaction of herbicides. Combination of saflufenacil with the herbicides tested in general did not change the response of both barnyardgrass biotypes to the herbicides used. The resistant biotype showed a lower negative effect on chlorophyll fluorescence and photosynthesis parameters in the combination of herbicides with saflufenacil. The herbicide cyhalofop was effective for the control of ALS-susceptible and resistant barnyardgrass.(AU)

O objetivo deste trabalho foi avaliar a interação entre herbicidas associados ao saflufenacil para o controle de capim-arroz e a determinação do efeito dos herbicidas sobre os parâmetros fotossintéticos e de fluorescência de clorofila. O experimento foi conduzido em casa de vegetação em esquema fatorial 2x8, cujo fator A testou os biótipos resistente e suscetível; e o fator B os herbicidas: saflufenacil (70 g i.a. ha-1), clomazone (180 g i.a. ha-1), imazapyr+imazapic (73,5+24,5 g i.a. ha-1), cyhalofop (360 g i.a. ha-1), as associações desses com saflufenacil, e testemunha sem tratamento. Foi avaliado o controle aos 7, 14, 21 e 28 dias após a aplicação dos herbicidas (DAA), massa seca da parte aérea aos 28 DAA, avaliação de parâmetros fotossintéticos com analisador de gás infravermelho (IRGA) e emissão de fluorescência da clorofila a 24 e 48 horas após aplicação dos tratamentos, respectivamente, e interação dos herbicidas. A associação de saflufenacil com herbicidas testados na maior parte não modificou a resposta dos herbicidas para o controle de capim-arroz em ambos os biótipos. O biótipo resistente apresentou menor efeito negativo nos processos de fluorescência de clorofila e parâmetros de fotossíntese na associação de herbicidas com saflufenacil. O herbicida cyhalofop associado ao saflufenacil demonstra ser eficiente para o controle de capim-arroz suscetível e resistente a ALS.(AU)

Barnyardgrass control using tank-mixed herbicides with saflufenacil and its influence in photosynthesis and chlorophyll fluorescence / Controle de capim-arroz mediante associações de herbicidas com saflufenacil e influência na fotossíntese e fluorescência de clorofila

ABSTRACT: The objectives of this research were to evaluate the interaction between herbicides mixed with saflufenacil for the control of barnyardgrass and to determine the effect on photosynthetic and chlorophyll fluorescence parameters. The experiment was conducted in a greenhouse in a 2x8 factorial scheme, whose factor A tested resistant and susceptible biotypes; and factor B the herbicides: saflufenacil (70 g a.i. ha-1), clomazone (180 g a.i. ha-1), imazapyr + imazapic (73.5 + 24.5 g a.i. ha-1), and cyhalofop (360 g a.i. ha-1), the mixtures of these herbicides with saflufenacil, and control without treatment. Weed control was assessed 7, 14, 21 and 28 days after herbicide application (DAA), as well as shoot dry matter at 28 DAA, photosynthetic parameters using infrared gas analyzer (IRGA), and emission of chlorophyll a fluorescence after 24 and 28 hours of application of treatments, respectively, and interaction of herbicides. Combination of saflufenacil with the herbicides tested in general did not change the response of both barnyardgrass biotypes to the herbicides used. The resistant biotype showed a lower negative effect on chlorophyll fluorescence and photosynthesis parameters in the combination of herbicides with saflufenacil. The herbicide cyhalofop was effective for the control of ALS-susceptible and resistant barnyardgrass.

RESUMO: O objetivo deste trabalho foi avaliar a interação entre herbicidas associados ao saflufenacil para o controle de capim-arroz e a determinação do efeito dos herbicidas sobre os parâmetros fotossintéticos e de fluorescência de clorofila. O experimento foi conduzido em casa de vegetação em esquema fatorial 2x8, cujo fator A testou os biótipos resistente e suscetível; e o fator B os herbicidas: saflufenacil (70 g i.a. ha-1), clomazone (180 g i.a. ha-1), imazapyr+imazapic (73,5+24,5 g i.a. ha-1), cyhalofop (360 g i.a. ha-1), as associações desses com saflufenacil, e testemunha sem tratamento. Foi avaliado o controle aos 7, 14, 21 e 28 dias após a aplicação dos herbicidas (DAA), massa seca da parte aérea aos 28 DAA, avaliação de parâmetros fotossintéticos com analisador de gás infravermelho (IRGA) e emissão de fluorescência da clorofila a 24 e 48 horas após aplicação dos tratamentos, respectivamente, e interação dos herbicidas. A associação de saflufenacil com herbicidas testados na maior parte não modificou a resposta dos herbicidas para o controle de capim-arroz em ambos os biótipos. O biótipo resistente apresentou menor efeito negativo nos processos de fluorescência de clorofila e parâmetros de fotossíntese na associação de herbicidas com saflufenacil. O herbicida cyhalofop associado ao saflufenacil demonstra ser eficiente para o controle de capim-arroz suscetível e resistente a ALS.

The antidepressant-like effect of guanosine is dependent on GSK-3ß inhibition and activation of MAPK/ERK and Nrf2/heme oxygenase-1 signaling pathways.

Although guanosine is an endogenous nucleoside that displays antidepressant-like properties in several animal models, the mechanism underlying its antidepressant-like effects is not well characterized. The present study aimed at investigating the involvement of ERK/GSK-3ß and Nrf2/HO-1 signaling pathways in the antidepressant-like effect of guanosine in the mouse tail suspension test (TST). The immobility time in the TST was taken as an indicative of antidepressant-like responses and the locomotor activity was assessed in the open-field test. Biochemical analyses were performed by Western blotting in the hippocampus and prefrontal cortex (PFC). The combined treatment with sub-effective doses of guanosine (0.01 mg/kg, p.o.) and lithium chloride (a non-selective GSK-3ß inhibitor, 10 mg/kg, p.o.) or AR-A014418 (selective GSK-3ß inhibitor, 0.01 µg/site, i.c.v.) produced a synergistic antidepressant-like effect in the TST. The antidepressant-like effect of guanosine (0.05 mg/kg, p.o.) was completely prevented by the treatment with MEK1/2 inhibitors U0126 (5 µg/site, i.c.v.), PD98059 (5 µg/site, i.c.v.), or zinc protoporphyrin IX (ZnPP) (HO-1 inhibitor, 10 µg/site, i.c.v). Guanosine administration (0.05 mg/kg, p.o.) increased the immunocontent of ß-catenin in the nuclear fraction and Nrf2 in the cytosolic fraction in the hippocampus and PFC. The immunocontent of HO-1 was also increased in the hippocampus and PFC. Altogether, the results provide evidence that the antidepressant-like effect of guanosine in the TST involves the inhibition of GSK-3ß, as well as activation of MAPK/ERK and Nrf2/HO-1 signaling pathways, highlighting the relevance of these molecular targets for antidepressant responses.

Weed phytosociological in irrigated rice under different cultivation systems and crop rotation intensity / Fitossociologia de plantas daninhas em arroz irrigado sob diferentes sistemas de cultivo e intensidade de rotação de culturas

This research aimed to evaluate the phytosociology of weeds in irrigated rice in different soil management systems and crop rotation intensity. Therefore, two field studies were carried out. Study 1 was conducted in an area that has been cultivated since 1994 with three cultivation systems: direct, pre-germinated and conventional ones. Study 2 was carried out in an experimental area in five Integrated Farming Systems, with crop rotation. Phytosociological evaluations were conducted when rice was fully blooming, in the first study, and when grain filling was ending, in the second study. Pre-germinated system of rice cultivation has predominance of aquatic weeds. Conventional system when compared with direct sowing has lower weed densities. Integrated Agricultural Production Systems with higher intensity of crop rotation have been higher infested of perennial species.(AU)

Este trabalho teve por objetivo avaliar a fitossociologia de plantas daninhas em arroz irrigado em diferentes sistemas de manejo do solo e intensidade de rotação de culturas. Para tanto, foram conduzidos dois estudos de campo. O primeiro estudo foi realizado em área cultivada desde 1994 com três sistemas de cultivo: plantio direto, pré-germinado e sistema convencional. O segundo estudo foi realizado em área experimental sob cinco Sistemas Integrados de Produção Agropecuária, com rotação de culturas. As avaliações fitossociológicas foram realizadas quando o arroz estava em pleno florescimento no primeiro estudo, e no final do enchimento de grãos no segundo. O sistema pré-germinado de cultivo de arroz apresenta predominância de plantas daninhas aquáticas. O sistema de cultivo convencional, quando comparado ao plantio direto, possui menores densidades de plantas daninhas. Nos Sistemas Integrados de Produção Agropecuária com maior intensidade de rotação de culturas houve maior infestação de plantas daninhas perenes.(AU)

Weed phytosociological in irrigated rice under different cultivation systems and crop rotation intensity / Fitossociologia de plantas daninhas em arroz irrigado sob diferentes sistemas de cultivo e intensidade de rotação de culturas

ABSTRACT: This research aimed to evaluate the phytosociology of weeds in irrigated rice in different soil management systems and crop rotation intensity. Therefore, two field studies were carried out. Study 1 was conducted in an area that has been cultivated since 1994 with three cultivation systems: direct, pre-germinated and conventional ones. Study 2 was carried out in an experimental area in five Integrated Farming Systems, with crop rotation. Phytosociological evaluations were conducted when rice was fully blooming, in the first study, and when grain filling was ending, in the second study. Pre-germinated system of rice cultivation has predominance of aquatic weeds. Conventional system when compared with direct sowing has lower weed densities. Integrated Agricultural Production Systems with higher intensity of crop rotation have been higher infested of perennial species.

RESUMO: Este trabalho teve por objetivo avaliar a fitossociologia de plantas daninhas em arroz irrigado em diferentes sistemas de manejo do solo e intensidade de rotação de culturas. Para tanto, foram conduzidos dois estudos de campo. O primeiro estudo foi realizado em área cultivada desde 1994 com três sistemas de cultivo: plantio direto, pré-germinado e sistema convencional. O segundo estudo foi realizado em área experimental sob cinco Sistemas Integrados de Produção Agropecuária, com rotação de culturas. As avaliações fitossociológicas foram realizadas quando o arroz estava em pleno florescimento no primeiro estudo, e no final do enchimento de grãos no segundo. O sistema pré-germinado de cultivo de arroz apresenta predominância de plantas daninhas aquáticas. O sistema de cultivo convencional, quando comparado ao plantio direto, possui menores densidades de plantas daninhas. Nos Sistemas Integrados de Produção Agropecuária com maior intensidade de rotação de culturas houve maior infestação de plantas daninhas perenes.