Mortality, morbidity, early recognition, and treatment of sepsis remain a diagnostic dilemma for clinicians, in addition, the timely diagnosis of sepsis represents an ongoing clinical challenge. This review looks at t...Mortality, morbidity, early recognition, and treatment of sepsis remain a diagnostic dilemma for clinicians, in addition, the timely diagnosis of sepsis represents an ongoing clinical challenge. This review looks at the challenges of early recognition, the scope of the problem, the immunologic basis of the sepsis cascade, new frontiers related to interventions, and the role of antibiotics in an era of antimicrobial resistance. In Figure 1, once a patient is on the slippery slope of sepsis, the ability to reverse the momentum is challenging;hoping antibiotics, fluid resuscitation, vasopressors may buy time for the immunologic cascade to equilibrate to its homeostatic balance. While the development of septic shock is much more complex than pathogen proliferation, our understanding of the pathogenesis and ability to therapeutically intervene is in its infancy. Patients with sepsis frequently present for urgent medical care with undifferentiated infection and nonspecific symptoms. As 80% of patients with sepsis are initially treated in an Emergency Department, the burden of early recognition and intervention falls squarely on the shoulders of Emergency Department Clinicians. [1] This is an entity that occurs in all age groups, without regard to race, geography, or health status. Survival and mortality related to this clinical entity are poorly understood. Our understanding of sepsis needs to expand beyond the downstream effects and collateral damage of multiorgan dysfunction and failure. Immunologically, the antigenic triggers, be it invasive infection, severe injury, and systemic inflammation without concomitant infection, elicit similar pattern recognition receptors and innate host responses. If you are lucky enough to have survived an acute episode of sepsis, patients with sepsis often develop new adverse sequelae after treatment, a concept called persistent critical illness or post sepsis syndrome, characterized by long-term disability, and worsening chronic health conditions requiring re-hospitalization. [2]展开更多
Neurodegenerative diseases are characterized by progressive degeneration and/or death of neuronal cells and results in a wide array of cognitive impairments and other serious neurological defects. The signaling pathwa...Neurodegenerative diseases are characterized by progressive degeneration and/or death of neuronal cells and results in a wide array of cognitive impairments and other serious neurological defects. The signaling pathways and definite cause underlying the development of neurodegenerative nerve diseases have not been well defined. There is evidence of mechanisms within the endocannabinoid system that may suggest important pathways involved the progression of neurodegenerative diseases as well as some cancers. The endocannabinoid system is an endogenous ubiquitous neuromodulatory system that plays a critical in the development of the central nervous system (CNS), synaptic plasticity, as well as other primary neuronal functions. The recent identification of various cannabinoid receptors and their endogenous lipid ligands has generated an interest and significant increase in research of the endocannabinoid system and its role in human health and diseases. The Endocannabinoid system possesses essential endogenous receptors—cannabinoid receptors type 1 (CB1R) and type 2 (CB2R)—which are involved in mechanisms that contribute to the progression of neurodegenerative diseases and some cancers. In this review, we discuss the role of the endocannabinoid system in various neurodegenerative diseases as well as some cancers, and its promise as a targeted pharmacological therapy for patients of neurodegenerative diseases.展开更多
<strong>Objective:</strong> Metals including arsenic, lead, mercury, and cadmium are toxic and can increase cardiovascular disease risk. High-sensitivity C-reactive protein (hs-CRP) is a biomarker for infl...<strong>Objective:</strong> Metals including arsenic, lead, mercury, and cadmium are toxic and can increase cardiovascular disease risk. High-sensitivity C-reactive protein (hs-CRP) is a biomarker for inflammation and cardiovascular risk. This study will evaluate the association between urinary speciated arsenic, cadmium, lead, and mercury and blood values of hs-CRP in the United States adult population. <strong>Methods:</strong> A cross-sectional study using the 2015-2016 NHANES dataset, conducting multivariate linear regressions to analyze selected urinary metals and links with serum hs-CRP. <strong>Results: </strong>The sample consisted of 780 adults. In adjusted models, arsenocholine was found to be protective of inflammation, whereas aresnous acid, which is an inorganic, toxic type of arsenic acid, was positively associated with hs-CRP (<em>b</em> = 2.53). <strong>Conclusion: </strong>Urinary arsenous acid is a significant predictor of hs-CRP which is a biomarker for CVD.展开更多
Arsenic is a known toxic chemical, has immuno-modulatory properties, and can change the susceptibility of infection in humans. Acute hepatitis E is an infectious disease;it can be self-limiting, but in severe cases, c...Arsenic is a known toxic chemical, has immuno-modulatory properties, and can change the susceptibility of infection in humans. Acute hepatitis E is an infectious disease;it can be self-limiting, but in severe cases, can cause acute-on-chronic liver failure. The presence of IgG anti-HEV (hepatitis E IgG antibody) in blood represents a past hepatitis E infection in an individual. Very few studies have investigated the association between arsenic levels and hepatitis E seroconversion in humans. The primary objective of this study was to assess the relationship between total urinary arsenic and speciated urinary arsenic (urinary arsenous acid, urinary arsenic acid, urinary arsenobetaine, urinary arsenocholine, urinary dimethylarsinic acid, urinary monomethylarsonic acid) and the presence of IgG anti-HEV. The 2011-2012, 2013-2014, and 2015-2016 National Health and Nutrition Examination Survey (NHANES) III data sets were analyzed, with participants aged 20 years and older (n = 7061). We used weighted logistic regression to determine the association between total and speciated urinary arsenic concentrations and IgG anti-HEV. For each analyte considered, a separate weighted logistic regression model was fitted. Each of these models regressed log-transformed analyte levels on the log-odds of the presence of IgG Anti-HEV. To evaluate the relationships between the urinary arsenic measurements, pairwise Pearson correlation coefficients were determined for each of the urinary arsenic measurements. Of the human subjects included, 6628 (93.9%) were negative for IgG Anti-HEV while 433 (6.1%) were positive for IgG anti-HEV. Total urinary arsenic was associated with 1.161 times greater odds of IgG anti-HEV (95% CI: [1.035, 1.303]) for each unit increase in concentration on a log-scale. For speciated urinary arsenic measurements, the odds ratios and 95% CI’s were: arsenobetanine 1.168 [1.075, 1.270], arsenocholine 1.201 [0.944, 1.529], dimethylarsinic acid 1.183 [1.009, 1.386], monomethylacrsonic acid 1.095 [0.915, 1.310], aresnous acid 0.907 [0.762, 1.079], and arsenic acid 1.951 [0.905, 4.209]. Our analysis indicates that total urinary arsenic, arsenobetanine, and dimethylarsinic acid are significantly associated with the odds of the presence of IgG anti-HEV. Future prospective studies are required to evaluate the association between hepatitis E infection and arsenic exposures.展开更多
Background and purpose C-C motif chemokine ligand 17(CCL17)presents an important role in immune regulation,which is critical in the pathophysiology of brain injury after subarachnoid haemorrhage(SAH).There is rare evi...Background and purpose C-C motif chemokine ligand 17(CCL17)presents an important role in immune regulation,which is critical in the pathophysiology of brain injury after subarachnoid haemorrhage(SAH).There is rare evidence to illustrate the function of CCL17 towards SAH.In this study,we try to reveal the therapeutic effects of CCL17 and its underlying mechanism in rat SAH model.Methods SAH rat models were assigned to receive recombinant CCL17(rCCL17)or phosphate buffer saline(PBS).AZD2098 and JR-AB2-011 were applied to investigate the C-C motif chemokine receptor 4(CCR4)/mammalian target of rapamycin complex 2(mTORC2)axis in CCL17-mediated neuroprotection.To elucidate the underlying mechanism,the in vitro kinase assay was performed in primary microglia.Microglial-specific Rictor knockdown was administered via intracerebroventricular injection of adenovirus-associated virus.Brain water content,short-term neurobehavioural evaluation,western blot analysis,quantitative RT-PCR and histological staining were performed.Results The expression of CCL17 was increased and secreted from neurons after oxyhaemoglobin stimulation.Exogenous rCCL17 significantly alleviated neuronal apoptosis,and alleviated short-term neurofunction after SAH in rats.In addition,rCCL17 increased M2-like polarisation of microglia in rats post-SAH and in primary microglia culture.The neuroprotection of rCCL17 was abolished via inhibition of either CCR4 or mTORC2.Conclusion CCL17 activated the CCR4/mTORC2 axis in microglia,which can alleviate SAH-induced neurological deficits by promoting M2-like polarisation of microglia.展开更多
Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes ...Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.展开更多
文摘Mortality, morbidity, early recognition, and treatment of sepsis remain a diagnostic dilemma for clinicians, in addition, the timely diagnosis of sepsis represents an ongoing clinical challenge. This review looks at the challenges of early recognition, the scope of the problem, the immunologic basis of the sepsis cascade, new frontiers related to interventions, and the role of antibiotics in an era of antimicrobial resistance. In Figure 1, once a patient is on the slippery slope of sepsis, the ability to reverse the momentum is challenging;hoping antibiotics, fluid resuscitation, vasopressors may buy time for the immunologic cascade to equilibrate to its homeostatic balance. While the development of septic shock is much more complex than pathogen proliferation, our understanding of the pathogenesis and ability to therapeutically intervene is in its infancy. Patients with sepsis frequently present for urgent medical care with undifferentiated infection and nonspecific symptoms. As 80% of patients with sepsis are initially treated in an Emergency Department, the burden of early recognition and intervention falls squarely on the shoulders of Emergency Department Clinicians. [1] This is an entity that occurs in all age groups, without regard to race, geography, or health status. Survival and mortality related to this clinical entity are poorly understood. Our understanding of sepsis needs to expand beyond the downstream effects and collateral damage of multiorgan dysfunction and failure. Immunologically, the antigenic triggers, be it invasive infection, severe injury, and systemic inflammation without concomitant infection, elicit similar pattern recognition receptors and innate host responses. If you are lucky enough to have survived an acute episode of sepsis, patients with sepsis often develop new adverse sequelae after treatment, a concept called persistent critical illness or post sepsis syndrome, characterized by long-term disability, and worsening chronic health conditions requiring re-hospitalization. [2]
文摘Neurodegenerative diseases are characterized by progressive degeneration and/or death of neuronal cells and results in a wide array of cognitive impairments and other serious neurological defects. The signaling pathways and definite cause underlying the development of neurodegenerative nerve diseases have not been well defined. There is evidence of mechanisms within the endocannabinoid system that may suggest important pathways involved the progression of neurodegenerative diseases as well as some cancers. The endocannabinoid system is an endogenous ubiquitous neuromodulatory system that plays a critical in the development of the central nervous system (CNS), synaptic plasticity, as well as other primary neuronal functions. The recent identification of various cannabinoid receptors and their endogenous lipid ligands has generated an interest and significant increase in research of the endocannabinoid system and its role in human health and diseases. The Endocannabinoid system possesses essential endogenous receptors—cannabinoid receptors type 1 (CB1R) and type 2 (CB2R)—which are involved in mechanisms that contribute to the progression of neurodegenerative diseases and some cancers. In this review, we discuss the role of the endocannabinoid system in various neurodegenerative diseases as well as some cancers, and its promise as a targeted pharmacological therapy for patients of neurodegenerative diseases.
文摘<strong>Objective:</strong> Metals including arsenic, lead, mercury, and cadmium are toxic and can increase cardiovascular disease risk. High-sensitivity C-reactive protein (hs-CRP) is a biomarker for inflammation and cardiovascular risk. This study will evaluate the association between urinary speciated arsenic, cadmium, lead, and mercury and blood values of hs-CRP in the United States adult population. <strong>Methods:</strong> A cross-sectional study using the 2015-2016 NHANES dataset, conducting multivariate linear regressions to analyze selected urinary metals and links with serum hs-CRP. <strong>Results: </strong>The sample consisted of 780 adults. In adjusted models, arsenocholine was found to be protective of inflammation, whereas aresnous acid, which is an inorganic, toxic type of arsenic acid, was positively associated with hs-CRP (<em>b</em> = 2.53). <strong>Conclusion: </strong>Urinary arsenous acid is a significant predictor of hs-CRP which is a biomarker for CVD.
文摘Arsenic is a known toxic chemical, has immuno-modulatory properties, and can change the susceptibility of infection in humans. Acute hepatitis E is an infectious disease;it can be self-limiting, but in severe cases, can cause acute-on-chronic liver failure. The presence of IgG anti-HEV (hepatitis E IgG antibody) in blood represents a past hepatitis E infection in an individual. Very few studies have investigated the association between arsenic levels and hepatitis E seroconversion in humans. The primary objective of this study was to assess the relationship between total urinary arsenic and speciated urinary arsenic (urinary arsenous acid, urinary arsenic acid, urinary arsenobetaine, urinary arsenocholine, urinary dimethylarsinic acid, urinary monomethylarsonic acid) and the presence of IgG anti-HEV. The 2011-2012, 2013-2014, and 2015-2016 National Health and Nutrition Examination Survey (NHANES) III data sets were analyzed, with participants aged 20 years and older (n = 7061). We used weighted logistic regression to determine the association between total and speciated urinary arsenic concentrations and IgG anti-HEV. For each analyte considered, a separate weighted logistic regression model was fitted. Each of these models regressed log-transformed analyte levels on the log-odds of the presence of IgG Anti-HEV. To evaluate the relationships between the urinary arsenic measurements, pairwise Pearson correlation coefficients were determined for each of the urinary arsenic measurements. Of the human subjects included, 6628 (93.9%) were negative for IgG Anti-HEV while 433 (6.1%) were positive for IgG anti-HEV. Total urinary arsenic was associated with 1.161 times greater odds of IgG anti-HEV (95% CI: [1.035, 1.303]) for each unit increase in concentration on a log-scale. For speciated urinary arsenic measurements, the odds ratios and 95% CI’s were: arsenobetanine 1.168 [1.075, 1.270], arsenocholine 1.201 [0.944, 1.529], dimethylarsinic acid 1.183 [1.009, 1.386], monomethylacrsonic acid 1.095 [0.915, 1.310], aresnous acid 0.907 [0.762, 1.079], and arsenic acid 1.951 [0.905, 4.209]. Our analysis indicates that total urinary arsenic, arsenobetanine, and dimethylarsinic acid are significantly associated with the odds of the presence of IgG anti-HEV. Future prospective studies are required to evaluate the association between hepatitis E infection and arsenic exposures.
基金the National Natural Science Foundation of China(81870916 and 81971107)the Fundamental Research Funds for the Central Universities,China(2019QNA7038).
文摘Background and purpose C-C motif chemokine ligand 17(CCL17)presents an important role in immune regulation,which is critical in the pathophysiology of brain injury after subarachnoid haemorrhage(SAH).There is rare evidence to illustrate the function of CCL17 towards SAH.In this study,we try to reveal the therapeutic effects of CCL17 and its underlying mechanism in rat SAH model.Methods SAH rat models were assigned to receive recombinant CCL17(rCCL17)or phosphate buffer saline(PBS).AZD2098 and JR-AB2-011 were applied to investigate the C-C motif chemokine receptor 4(CCR4)/mammalian target of rapamycin complex 2(mTORC2)axis in CCL17-mediated neuroprotection.To elucidate the underlying mechanism,the in vitro kinase assay was performed in primary microglia.Microglial-specific Rictor knockdown was administered via intracerebroventricular injection of adenovirus-associated virus.Brain water content,short-term neurobehavioural evaluation,western blot analysis,quantitative RT-PCR and histological staining were performed.Results The expression of CCL17 was increased and secreted from neurons after oxyhaemoglobin stimulation.Exogenous rCCL17 significantly alleviated neuronal apoptosis,and alleviated short-term neurofunction after SAH in rats.In addition,rCCL17 increased M2-like polarisation of microglia in rats post-SAH and in primary microglia culture.The neuroprotection of rCCL17 was abolished via inhibition of either CCR4 or mTORC2.Conclusion CCL17 activated the CCR4/mTORC2 axis in microglia,which can alleviate SAH-induced neurological deficits by promoting M2-like polarisation of microglia.
文摘Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.
