Rhythms in immunity manifest in multiple ways, but perhaps most prominently by the recurrent onset of inflammation at specific times of day. These patterns are of importance to understand human disease and are caused, in many instances, by the action of neutrophils, a myeloid leukocyte with striking circadian features. The neutrophil's short life, marked diurnal variations in number, and changes in phenotype while in the circulation, help explain the temporal features of inflammatory disease but also uncover core features of neutrophil physiology. Here, we summarize well-established concepts and introduce recent discoveries in the biology of these cells as they relate to circadian rhythms. We highlight that although the circadian features of neutrophils are better known and relevant to understand disease, they may also influence important aspects of organ function even in the steady-state. Finally, we discuss the possibility of targeting these temporal features of neutrophils for therapeutic benefit. Copyright © 2020 Aroca-Crevillén, Adrover and Hidalgo.T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric malignancy that arises from the transformation of immature T-cell progenitors and has no definitive cure. Notch signaling governs many steps of T cell development and its dysregulation represents the most common causative event in the pathogenesis of T-ALL. The activation of canonical NF-κB pathway has been described as a critical downstream mediator of Notch oncogenic functions, through the sustaining of tumor cell survival and growth. The potential role of Notch/NF-κB partnership is also emerging in the generation and function of regulatory T cells (Tregs) in the context of cancer. However, little is known about the effects of combined mutations of Notch and NF-κB in regulating immune-environment and progression of T-ALL. To shed light on the topics above we generated double-mutant ****, harboring conventional knock-out mutation of NF-κB1/p50 on the genetic background of a transgenic model of Notch-dependent T-ALL. The immunophenotyping heir apoptotic rate. https://www.selleckchem.com/products/tak-715.html In conclusion, double-mutant **** may represent a useful model to deepen the knowledge of the consequences on T-ALL immune-environment of modulating Notch/NF-κB relationships in tumor cells. More importantly, information derived from these studies may help in the refinement of multitarget therapies for the disease. Copyright © 2020 Grazioli, Orlando, Giordano, Noce, Peruzzi, Scafetta, Screpanti and Campese.There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr ****, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr **** were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus **** with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr ****. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment. Copyright © 2020 Zhang, Liu, Yu, Wang, Wen and He.Temporal development of the human gut microbiome from infancy to childhood is driven by a variety of factors. We surveyed the fecal microbiome of 729 Chinese children aged 0-36 months, aiming to identify the age-specific patterns of microbiota succession, and evaluate the impact of birth mode, gender, geographical location, and gastrointestinal tract symptoms on the shaping of the gut microbiome. We demonstrated that phylogenetic diversity of the gut microbiome increased gradually over time, which was accompanied by an increase in Bacteroidetes and a reduction in Proteobacteria species. Analysis of community-wide phenotypes revealed a succession from aerobic bacteria and anaerobic bacteria to facultative anaerobes, and from Gram-negative to Gram-positive species during gut microbiota development in early childhood. The metabolic functions of the gut microbiome shifted tremendously alongside early physiological development, including an increase in alanine, aspartate, and glutamate metabolism, and a reduction diarrhea. Copyright © 2020 Niu, Xu, Qian, Sun, Yu, Huang, Zhou, Wang, Zhang, Ren, Li, Yu and Gao.Abnormalities related to peripartum depression (PPD) have been detected in several brain regions through tasking-state functional magnetic resonance imaging (fMRI). In this study, we used the two markers of resting-state fMRI (rs-fMRI) to investigate changes in spontaneous neural activity of PPD and their correlation with depression severity. A total of 16 individuals with PPD were compared with 16 age- and education-matched healthy controls (HCs) by using rs-fMRI. Two-sample t-test was used to compare the fractional amplitudes of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the fALFF and ReHo of the abnormal brain region and the Hamilton Depression Scale (HAMD) and Edinburgh Postnatal Depression Scale scores. The spontaneous neural activity of the PPD group significantly increased mainly in the left middle frontal gyrus, left precuneus, left inferior parietal lobule, and left dorsolateral prefrontal cortex (DLPFC) and decreased mainly in the bilateral precentral gyrus and right inferior occipital gyrus compared with those of the HCs. The fALFF value of the left DLPFC was negatively correlated with the HAMD score in PPD. This rs-fMRI study suggests that changes in the spontaneous neural activity of these regions are related to emotional responses. PPD cases with low fALFF values in the left DLPFC have severe depression. Copyright © 2020 Che, Mao, Li, Liu, Ma, Bai, Xu, Dong, Li, Shi and Xie.
Rhythms in immunity manifest in multiple ways, but perhaps most prominently by the recurrent onset of inflammation at specific times of day. These patterns are of importance to understand human disease and are caused, in many instances, by the action of neutrophils, a myeloid leukocyte with striking circadian features. The neutrophil's short life, marked diurnal variations in number, and changes in phenotype while in the circulation, help explain the temporal features of inflammatory disease but also uncover core features of neutrophil physiology. Here, we summarize well-established concepts and introduce recent discoveries in the biology of these cells as they relate to circadian rhythms. We highlight that although the circadian features of neutrophils are better known and relevant to understand disease, they may also influence important aspects of organ function even in the steady-state. Finally, we discuss the possibility of targeting these temporal features of neutrophils for therapeutic benefit. Copyright © 2020 Aroca-Crevillén, Adrover and Hidalgo.T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric malignancy that arises from the transformation of immature T-cell progenitors and has no definitive cure. Notch signaling governs many steps of T cell development and its dysregulation represents the most common causative event in the pathogenesis of T-ALL. The activation of canonical NF-κB pathway has been described as a critical downstream mediator of Notch oncogenic functions, through the sustaining of tumor cell survival and growth. The potential role of Notch/NF-κB partnership is also emerging in the generation and function of regulatory T cells (Tregs) in the context of cancer. However, little is known about the effects of combined mutations of Notch and NF-κB in regulating immune-environment and progression of T-ALL. To shed light on the topics above we generated double-mutant mice, harboring conventional knock-out mutation of NF-κB1/p50 on the genetic background of a transgenic model of Notch-dependent T-ALL. The immunophenotyping heir apoptotic rate. https://www.selleckchem.com/products/tak-715.html In conclusion, double-mutant mice may represent a useful model to deepen the knowledge of the consequences on T-ALL immune-environment of modulating Notch/NF-κB relationships in tumor cells. More importantly, information derived from these studies may help in the refinement of multitarget therapies for the disease. Copyright © 2020 Grazioli, Orlando, Giordano, Noce, Peruzzi, Scafetta, Screpanti and Campese.There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment. Copyright © 2020 Zhang, Liu, Yu, Wang, Wen and He.Temporal development of the human gut microbiome from infancy to childhood is driven by a variety of factors. We surveyed the fecal microbiome of 729 Chinese children aged 0-36 months, aiming to identify the age-specific patterns of microbiota succession, and evaluate the impact of birth mode, gender, geographical location, and gastrointestinal tract symptoms on the shaping of the gut microbiome. We demonstrated that phylogenetic diversity of the gut microbiome increased gradually over time, which was accompanied by an increase in Bacteroidetes and a reduction in Proteobacteria species. Analysis of community-wide phenotypes revealed a succession from aerobic bacteria and anaerobic bacteria to facultative anaerobes, and from Gram-negative to Gram-positive species during gut microbiota development in early childhood. The metabolic functions of the gut microbiome shifted tremendously alongside early physiological development, including an increase in alanine, aspartate, and glutamate metabolism, and a reduction diarrhea. Copyright © 2020 Niu, Xu, Qian, Sun, Yu, Huang, Zhou, Wang, Zhang, Ren, Li, Yu and Gao.Abnormalities related to peripartum depression (PPD) have been detected in several brain regions through tasking-state functional magnetic resonance imaging (fMRI). In this study, we used the two markers of resting-state fMRI (rs-fMRI) to investigate changes in spontaneous neural activity of PPD and their correlation with depression severity. A total of 16 individuals with PPD were compared with 16 age- and education-matched healthy controls (HCs) by using rs-fMRI. Two-sample t-test was used to compare the fractional amplitudes of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) values between groups. Pearson correlation analysis was used to determine the correlation between the fALFF and ReHo of the abnormal brain region and the Hamilton Depression Scale (HAMD) and Edinburgh Postnatal Depression Scale scores. The spontaneous neural activity of the PPD group significantly increased mainly in the left middle frontal gyrus, left precuneus, left inferior parietal lobule, and left dorsolateral prefrontal cortex (DLPFC) and decreased mainly in the bilateral precentral gyrus and right inferior occipital gyrus compared with those of the HCs. The fALFF value of the left DLPFC was negatively correlated with the HAMD score in PPD. This rs-fMRI study suggests that changes in the spontaneous neural activity of these regions are related to emotional responses. PPD cases with low fALFF values in the left DLPFC have severe depression. Copyright © 2020 Che, Mao, Li, Liu, Ma, Bai, Xu, Dong, Li, Shi and Xie.
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