Interpretation of the World Society of the Emergency Surgery/the Global Alliance for Infection in Surgery/the Surgical Infection Society-Europe/the World Surgical Infection Society/the American Association for the Surgery of Trauma global clinical pathways for patients with intra- abdominal infections / 中华危重病急救医学

Intra-abdominal infections (IAI) is common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The principles of IAI management included early diagnosis, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using critical care resources, combined with an optimal surgical approach. In order to facilitate clinical management, establish a global standard and provide guidance for clinicians, the World Society of Emergency Surgery (WSES), the Global Alliance for Infection in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) worked together to complete an international multi-society document, which provided the evidence-based clinical pathways. Herein, we made a comprehensive interpretation for the clinical pathways combined with the latest domestic and international research developments, aiming to provide evidence for domestic doctors on the diagnosis and treatment of IAI, and ultimately benefit patients.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Effect of asiaticoside on OGD/R induced injury of H9C2 cardiomyocytes based on PI3K/Akt/Beclin-1 signaling pathway / 药学学报

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L-1), Ass high concentration group (80 μmol·L-1) and Ass high concentration + chloroquine group (80 μmol·L-1 + 50 μmol·L-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

The coronary heart disease of phlegm-stasis cementation syndrome in mini-swine based on platelet proteomics / 药学学报

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

Inhibitory effects of GT0918 on acute lung injury and the molecular mechanisms of anti-inflammatory response

Coronavirus disease 2019 (COVID-19) has caused the public health crisis in the whole world. Anti-androgens block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and protect against severe clinical COVID-19 outcomes. GT0918, a novel androgen receptor antagonist, accelerated viral clearance and increased recovery rate in outpatients by blocking SARS-CoV-2 infection though down-regulating ACE2 and TMPRSS2 expression. Further clinical study showed that GT0918 reduced mortality rate and shortened hospital stay in hospitalized COVID-19 patients. GT0918 also exhibits protective efficacy in severe COVID-19 patient in critical care. However, the mechanism of GT0918 treatment for severe COVID-19 disease is unknown. Here, we found GT0918 decreased the expression and secretion of proinflammatory cytokines through NF-{kappa}B signaling pathway. The acute lung injury induced by LPS or Poly(I:C) was also attenuated in GT0918-treated mice, compared with vehicle control group. Moreover, GT0918 elevated the NRF2 protein level but not mRNA transcription activity. GT0918 induced proinflammatory cytokines downregulation was partially dependent on NRF2. In conclusion, our data demonstrate that GT0918 reduced cytokine release and suppressed inflammatory responses through inhibiting NF-{kappa}B signaling and activating NRF2. GT0918 is not only effective for treatment of mild to moderate COVID-19 patients, but also a potential therapeutic drug for severe COVID-19 patients by reducing the risk of cytokine storm and acute respiratory distress syndrome.

Mechanisms of pruritus in atopic dermatitis / 中华皮肤科杂志

Pruritus in atopic dermatitis (AD) is typical non-histaminergic itch involving complex nerve pathways. A variety of cytokines and neuropeptides, skin barrier dysfunction and skin microbiome imbalance are also involved in the generation and transmission of itching-relatd signals. This review focuses on main research progress in the pathogenesis and treatment of pruritus in AD in recent years.

Assessment of macular vascular network after panretinal photocoagulation in the patients with diabetic retinopathy by OCTA / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the differences of macular vascular network measured by optical coherence tomography angiography(OCTA)between severe non-proliferative diabetic retinopathy(S-NPDR)eyes and health eyes, and explore the changes of these OCTA characteristics in patients with S-NPDR before and after panretinal photocoagulation(PRP).<p>METHODS: This was a prospective study including 31 eyes from 18 consecutive patients with S-NPDR and 31 eyes of healthy subjects. We measured macular vascular density and foveal avascular zone(FAZ)area and volume by an OCTA device.<p>RESULTS: Compared to the normal control group, in superficial retinal capillary plexus(SCP), macular vascular density decreased in S-NPDR group, except foveal vascular density unchanged. Consistently, in deep retinal capillary plexus(DCP), macular vascular density was also lower in S-NPDR group. In addition, FAZ area and volume expanded in S-NPDR eyes. At 6mo post-PRP in S-NPDR eyes, foveal SCP and DCP densities increased significantly, while FAZ area and volume decreased. At 3mo post-PRP, only foveal vascular density in DCP increased. The changes of foveal SCP and DCP densities as well as FAZ area and volume were not statically significant at 1mo post-PRP.<p>CONCLUSION: Macular vascular network was impaired in S-NPDR assessed by OCTA. Although OCTA parameters were not significantly affected by PRP in 1 and 3mo period, at 6mo follow-up parameters became significant after PRP.

Correlation between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials / 中国骨伤

OBJECTIVE@#To analyze the relationship between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials(VEMPs) and analyze the correlations between cervical vertigo and vestibular dysfunction, discuss the related factors of cervical vertigo and guide the clinical treatment of patients with cervical vertigo.@*METHODS@#A total of 75 patients with cervical vertigo as the main complaint in the outpatient clinic of the Second Hospital of Shanxi Medical University from August 2019 to July 2020 were set as the diseased group, and 60 patients without cervical and vestibular related diseases in the hospital were selected to set as non-diseased group. The age of diseased group was 12 to 70 years with an average of (46.40±10.91) years, including 25 males and 50 females;and the age of non-diseased group was 22 to 60 years with an average of(43.78±7.75) years, including 19 males and 51 females. VEMPs were performed in the two groups. The data of VEMPs were collected and the results were compared and analyzed. The patients with abnormal cervical myogenic vestibular evoked myogenic potential (cVEMP) were divided into light, moderate and severe groups. The correlation between VEMPs and cervical vertigo and its severity were analyzed by statistical method.@*RESULTS@#(1)The severity of cervical vertigo in diseased group:33 cases of mild, 34 cases of moderate, 8 cases of severe; cVEMP examination:62 cases were positive and 13 cases were negative, including 13 cases of mild, 33 cases of moderate, 16 cases of severe. The cVEMP of non-diseased group:4 cases were positive and 56 cases were negative.(2) The level of cVEMP in diseased group was higher than that in non-diseased group (P<0.001). It can be considered that there was a correlation between cervical vertigo and vestibular function.(3)The correlation between the level of cVEMP and the level of cervical vertigo in diseased group was analyzed. The Spearman rank sum test was used, and the correlation coefficient was 0.687, which was statistically significant (P<0.05). And it can be considered that the two indicators have a high degree of correlation.@*CONCLUSION@#It is feasible to evaluate the relationship between cervical vertigo and vestibular function by VEMPs. For patients with cervical vertigo, the higher the severity, the greater the positive rate of VEMPs, which indicates that it has a greater impact on vestibular function. The treatment of patients with cervical vertigo should be the combination of cervical rehabilitation and vestibular function.

Ocular images for neurodegenerative disease analysis / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retina and optic nerve both originate in brain, therefore they have the similar structure and functional characteristics of the brain. Exploring the performance of the central optic nervous disorder on the retina will be beneficial to uncovering the interaction mechanism between brain and eye. As an extension of the central nervous system, the retina contains ganglion cell, a special neuron, whose axon form the optic nerve and has access into the central nervous system. Therefore, the retina can be used as a mirror reflecting neurodegenerative diseases structurally and functionally. With the development of imaging technology, optical coherence tomography(angiography)has become the mainstream tool for ophthalmological clinical diagnosis due to its easy operation and low cost. In recent years, discovering biomarkers of neurodegenerative diseases, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis and so on, in the retinal optical coherence tomography images has gradually become an emerging research direction. In this review, we summarized the research progress of neurodegenerative diseases analysis based on the retinal images in the past decade, and provide a prospect to inspire further research as far as possible.

IL-17A injury to retinal ganglion cells is mediated by retinal Müller cells in diabetic retinopathy.

Diabetic retinopathy (DR), the most common and serious ocular complication, recently has been perceived as a neurovascular inflammatory disease. However, role of adaptive immune inflammation driven by T lymphocytes in DR is not yet well elucidated. Therefore, this study aimed to clarify the role of interleukin (IL)-17A, a proinflammatory cytokine mainly produced by T lymphocytes, in retinal pathophysiology particularly in retinal neuronal death during DR process. Ins2Akita (Akita) diabetic mice 12 weeks after the onset of diabetes were used as a DR model. IL-17A-deficient diabetic mice were obtained by hybridization of IL-17A-knockout (IL-17A-KO) mouse with Akita mouse. Primarily cultured retinal Müller cells (RMCs) and retinal ganglion cells (RGCs) were treated with IL-17A in high-glucose (HG) condition. A transwell coculture of RGCs and RMCs whose IL-17 receptor A (IL-17RA) gene had been silenced with IL-17RA-shRNA was exposed to IL-17A in HG condition and the cocultured RGCs were assessed on their survival. Diabetic mice manifested increased retinal microvascular lesions, RMC activation and dysfunction, as well as RGC apoptosis. IL-17A-KO diabetic mice showed reduced retinal microvascular impairments, RMC abnormalities, and RGC apoptosis compared with diabetic mice. RMCs expressed IL-17RA. IL-17A exacerbated HG-induced RMC activation and dysfunction in vitro and silencing IL-17RA gene in RMCs abolished the IL-17A deleterious effects. In contrast, RGCs did not express IL-17RA and IL-17A did not further alter HG-induced RGC death. Notably, IL-17A aggravated HG-induced RGC death in the presence of intact RMCs but not in the presence of RMCs in which IL-17RA gene had been knocked down. These findings establish that IL-17A is actively involved in DR pathophysiology and particularly by RMC mediation it promotes RGC death. Collectively, we propose that antagonizing IL-17RA on RMCs may prevent retinal neuronal death and thereby slow down DR progression.

Facile construction of dual heterojunction CoO@TiO2/MXene hybrid with efficient and stable catalytic activity for phenol degradation with peroxymonosulfate under visible light irradiation.

Photocatalysis and peroxymonosulfate (PMS) based advanced oxidation processes (AOP) are emerging technology for the degradation of refractory organic pollutant in the field of water treatment. Here we report a novel CoO@TiO2/MXene (CTM) hybrid through a facile sonication-hydrothermal method for efficient degradation of phenol via an integrated PMS activation-photocatalysis process. Benefiting from the proper position and superior suitability of the band structure, a dual interfacial charge transport channel was constructed, boosting the separation of photo-generated charge carriers and generating sufficient potential difference for redox reaction. Accordingly, the CTM hybrid not only possessed the outstanding photocatalytic activity but also dramatically accelerated PMS activation to generate considerable reactive radicals. As a result, over 96% phenol degradation was achieved in the 10% CTM/PMS/Vis system within 15 min. The radical quenching test and EPR analysis reveal that SO4•-, O2•- and 1O2 were predominant reactive species involved in the catalytic process. Moreover, the damaged chemical structure of CoO during PMS activation could be healed by the photo-actuated Co(II) regeneration to allow for continuous and stable catalytic process. This study offers a promising perspective for the rational design of competent and stable hybrid heterojunction catalyst to construct PMS activation-photocatalysis processes for the efficient degradation of organic contaminants.

IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA.

IMPACT STATEMENT: The participation of interleukin (IL)-17A in diabetic pathogenesis is suggested in animal models of autoimmune diabetes and in patients with type 1 diabetes (T1D), but with some contradictory results. Particularly, evidence for a direct injury of IL-17A to pancreatic ß cells is lacking. We showed that IL-17A deficiency alleviated diabetic signs including hyperglycemia, hypoinsulinemia, and inflammatory response in Ins2Akita (Akita) mice, a T1D model with spontaneous mutation in insulin 2 gene leading to ß-cell apoptosis. IL-17A enhanced inflammatory reaction, oxidative stress, and cell apoptosis but attenuated insulin level in mouse insulin-producing MIN6 cells. IL-17A had also a synergistic destruction to MIN6 cells with streptozotocin (STZ), a pancreatic ß-cell-specific cytotoxin. Blocking IL-17 receptor A (IL-17RA) reduced all these deleterious effects of IL-17A on MIN6 cells. The results demonstrate the role and the importance of IL-17A in T1D pathogenesis and suggest a potential therapeutic strategy for T1D targeting IL-17A and/or IL-17RA.

Comparative study of dose distributions calculated by dual optimization modes of Monaco system by volumetric modulated arc therapy of nasopharyngeal carcinoma / 中国辐射卫生

Objective To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) of Monaco planning system for nasopharyngeal carcinoma between Pareto and Constrained optimization in order to provide a reference for future mode selection. Methods Select 20 patients with nasopharyngeal carcinoma whom were calculated by Pareto and Constrained modes in the same CT image. Prescription dose of target PGTV, PTV1 and PTV2 was 70.29、60.39 and 54.45 Gy with 33 fractions, 5 times a week. The differences in target dose, organs at-risk dose, monitor units and segments were compared in the condition of 95% of the target volume reached the prescribed dose. Results Compared with Pareto group, Constrained group achieved a better HI and CI. CI of PGTV and PTV1 signed statistical differences (P < 0.05). Dose of OARs in Constrained group were all lower than those in Pareto group except Optical-l and lens-l. The differences of spinal cord prv dose and V30 of Parotid-r between two groups was significant (P < 0.05) while the differences of monitor units and segments between two groups was not significant (P > 0.05). Conclusion The length of middle turbinate is negatively correlated with the occurrence and severity of CMS. There is no significant correlation between the degree of curling and the occurrence of CMS, but patients with lower degree of curling of middle turbinate may have more serious CMS.

Acute gallstone pancreatitis caused by duodenal papillary impacted stone: a study on its risk factors based on ERCP findings / 中华肝胆外科杂志

Objective:To study the risk factors of acute gallstone pancreatitis (AGP) caused by impaction of duodenal papilla stones based on ERCP findings to provide evidence on prevention of AGP caused by stone impaction.Methods:The data of 304 patients with duodenal papilla stone impaction who were treated by ERCP at the Integrated Chinese and Western Medicine Hospital of Tianjin University from January 2009 to December 2020 were analyzed retrospectively. There were 177 males and 127 females, with a median age of 65.0 years. These patients were divided into the AGP group ( n=174) and the non-AGP group ( n=130) according to whether they developed acute pancreatitis before hospitalization. The analysis was performed on perioperative data. Multivariate logistic regression analysis was used to detect risk factors of AGP in patients with duodenal papillary stone impaction. Results:Multivariate logistic analysis showed that acute cholangitis ( OR=2.114, 95% CI: 1.279-3.494, P<0.05) and impacted stones ≤5 mm ( OR=1.738, 95% CI: 1.064-2.840, P<0.05) were independent risk factors of duodenal papillary stone impaction complicated with AGP. No perforation and death related to ERCP treatment occurred in both groups. The symptom alleviating time of patients in the AGP versus the non-AGP groups was (2.67±1.19) versus (1.88±0.88) d respectively ( t=-6.321, P<0.001). Conclusion:Among patients with duodenal papilla impacted stones, acute cholangitis and impacted stones ≤5 mm were risk factors of developing AGP, and ERCP should be carried out as early as possible.

Research progress on Chinese medicinal material-derived active polypeptides against ischemic cardiovascular and cerebrovascular diseases / 中国中药杂志

Ischemic cardiovascular and cerebrovascular diseases threatening human health and survival have high morbidity and mortality. The common cause of them is reduced blood supply caused by vascular stenosis, atherosclerosis, and infarction. However,the pathological processes of ischemic cardiovascular and cerebrovascular diseases are complex, involving oxidative stress, calcium overload, inflammation, apoptosis, autophagy and other mechanisms. Protein drugs such as recombinant tissue plasminogen activator(rt-PA) and urokinase have been proved with excellent therapeutic effects and huge economic and social benefits in the clinical treatment and interventional therapy. Among them, peptide drugs have shown unique advantages and potential prospects owing to their strong biological activity, high target specificity, biochemical diversity, and low toxicity. Chinese medicinal materials, characterized by multi-component and multi-target therapy, have also shown excellent clinical efficacy against ischemic cardiovascular and cerebrovascular diseases. However, the research and development of related peptides in Chinese medicinal materials is at the initial stage. Therefore, this paper reviewed the targets and action mechanisms of a variety of Chinese medicinal material-derived polypeptides with activities against ischemic cardiovascular and cerebrovascular diseases, aiming to provide support for the in-depth research as well as the clinical development and application of these polypeptides.

IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson's disease.

Neuroinflammation has been involved in pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disease characterized neuropathologically by progressive dopaminergic neuronal loss in the substantia nigra (SN). We recently have shown that helper T (Th)17 cells facilitate dopaminergic neuronal loss in vitro. Herein, we demonstrated that interleukin (IL)-17A, a proinflammatory cytokine produced mainly by Th17 cells, contributed to PD pathogenesis depending on microglia. Mouse and rat models for PD were prepared by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or striatal injection of 1-methyl-4-phenylpyridinium (MPP+), respectively. Both in MPTP-treated mice and MPP+-treated rats, blood-brain barrier (BBB) was disrupted and IL-17A level increased in the SN but not in cortex. Effector T (Teff) cells that were adoptively transferred via tail veins infiltrated into the brain of PD mice but not into that of normal mice. The Teff cell transfer aggravated nigrostriatal dopaminergic neurodegeneration, microglial activation and motor impairment. Contrarily, IL-17A deficiency alleviated BBB disruption, dopaminergic neurodegeneration, microglial activation and motor impairment. Anti-IL-17A-neutralizing antibody that was injected into lateral cerebral ventricle in PD rats ameliorated the manifestations mentioned above. IL-17A activated microglia but did not directly affect dopaminergic neuronal survival in vitro. IL-17A exacerbated dopaminergic neuronal loss only in the presence of microglia, and silencing IL-17A receptor gene in microglia abolished the IL-17A effect. IL-17A-treated microglial medium that contained higher concentration of tumor necrosis factor (TNF)-α facilitated dopaminergic neuronal death. Further, TNF-α-neutralizing antibody attenuated MPP+-induced neurotoxicity. The findings suggest that IL-17A accelerates neurodegeneration in PD depending on microglial activation and at least partly TNF-α release.

Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents.

BACKGROUND/AIMS: Interleukin (IL)-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR), one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function. METHODS: High glucose (HG)-treated rat Müller cell line (rMC-1) was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb) or/and anti-IL-17 receptor (R)A-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ). DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection. RESULTS: IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina. CONCLUSIONS: IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR.

IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling.

Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2Akita (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.

IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling

Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.

Waste electrical and electronic equipment management in Botswana: Prospects and challenges.

The management of waste electronic and electrical equipment (WEEE) is a major challenge in developing and transition countries. The paper investigates recent strategies to manage this waste stream in an environmentally sound way. Obsolete electrical and electronic equipment (EEE) are a complex waste category containing both hazardous and valuable substances. Many countries and regions in the world are undertaking extensive scientific research to plan and develop effective collection and treatment systems for end-of-life EEE. In developing countries such as Botswana, effective strategies that cover all stages throughout the lifecycle of products, particularly at the end-of-life, still lag behind. Infrastructure, pre-processing, and end-processing facilities and innovative technologies for end-of-life management of e-waste are noticeably absent due to lack of investment and high costs of its management. The objective of the paper is to present the e-waste situation in Botswana, highlighting (a) measures taken in the form of legislative and policy regulations; (b) existing practices to manage e-waste; and (c) effective solutions for e-waste management in emerging economies. Studies from other countries on e-waste management issues provided insights on the "best" technical and logistical pre-processing and end-processing strategies to treat hazardous waste. The paper also highlights key societal factors that affect successful implementation of cost-effective collection and value recovery of end-of-life EEE. These include unavailability of national "e-waste policy," absence of formal take-back system, absence of financing and subsidies, inadequate source separation programmes, absence of technical and logistical integration of pre-processing and end-processing facilities, and limited infrastructure and access to technologies and investment. Effective strategies such as an "integrated approach" (mixed options), access to technologies, establishment of pre-processing and end-processing facilities and optimization of logistics, optimizing diversion of e-waste from disposal sites, and investment in e-waste are suggested to manage this complex waste stream in an environmentally sound way.