Cdk5 activation promotes Cos-7 cells transition towards neuronal-like cells.

Objectives: Cyclin-dependent kinase 5 (Cdk5) activity is specifically active in neurogenesis, and Cdk5 and neocortical neurons migration related biomarker are expressed in Cos-7 cells. However, the function of Cdk5 on the transformation of immortalized Cos-7 cells into neuronal-like cells is not clear. Methods: Cdk5 kinase activity was measured by [γ-32P] ATP and p81 phosphocellulose pads based method. The expression of neuron liker markers was evaluated by immunofluorescence, real-time PCR, Western blot, and Elisa. Results: P35 overexpression upregulated Cdk5 kinase activity in Cos-7 cells. p35 mediated Cdk5 expression promoted the generation of nerite-like outgrowth. Compared with the empty vector, p35-induced Cdk5 activation resulted in time-dependent increase in neuron-like marker, including Tau, NF-H, NF-H&M, and TuJ1. Tau-5 and NF-M exhibited increased expression at 48 h while TuJ1 was only detectable after 96 h in p35 expressed Cos-7 cells. Additionally, the neural cell biomarkers exhibited well colocation with p35 proteins. Next-generation RNA sequence showed that p35 overexpression significantly upregulated the level of nerve growth factor (NGF). Gene set enrichment analysis showed significant enrichment of multiple neuron development pathways and increased NGF expression after p35 overexpression. Conclusion: p35-mediated Cdk5 activation promotes the transformation of immortalized Cos-7 cells into neuronal-like cells by upregulating NGF level.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Acupuncture ameliorates Mobile Phone Addiction with sleep disorders and restores salivary metabolites rhythm.

Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.

Platelet-to-albumin ratio is a potential biomarker for predicting diabetic nephropathy in patients with type 2 diabetes.

Aim: To evaluate whether platelet-to-albumin ratio (PAR) can predict diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). Materials & methods: A total of 140 patients with T2DM and 40 healthy individuals were enrolled retrospectively. T2DM patients were divided into three groups based on the urinary albumin-to-creatinine ratio, PAR was compared and receiver operating characteristic curve was constructed to evaluate the predictive value of PAR in DN in T2DM. Results: There was a significant increase of PAR in DN among T2DM patients and PAR was positively correlated with serum creatinine, retinol-conjugated protein and ß2-microglobulin. Moreover, PAR was a risk factor for DN in T2DM patients, which predicted DN in T2DM with high sensitivity and specificity. Conclusion: PAR can be a potential candidate to predict DN in T2DM.

Copper(II)-Doped Two-Dimensional Titanium-Based Metal-Organic Frameworks toward Light-Driven CO2 Reduction to Value-Added Products.

Recently, metal-organic framework (MOF)-based photocatalysts for an efficient CO2 reduction reaction have drawn wide attention in multidisciplinary fields and sustainable chemistry. In this work, a series of Cu2+-doped two-dimensional Ti-based MOFs were fabricated by a facile in situ solvothermal method. Cu2+ ions were doped in equal proportions and uniformly dispersed in the crystal structure of the MOF matrix. Interestingly, the doping content of Cu2+ ions and the photocatalytic performance displayed an obvious volcanic relationship, the medium-concentration Cu2+-doped sample (T1-2Cu) held the greatest activity with 100% carbonaceous product (CH4 and CO) formation, and the CH4 production rate was 3.7 µmol g-1 h-1 with 93% electron selectivity. The band structure, local electronic structure, carrier separation kinetics, and CO2 adsorption studies demonstrated that the excellent photocatalytic activity of T1-2Cu benefited from the appropriate amount of Cu2+ ion doping: (1) a doping amount of 2 atom % optimized the conduction band position of the MOF substrate and endowed T1-2Cu with strong reduction potential in thermodynamics, (2) doping Cu2+ ions tuned the local electronic environment around titanium oxide clusters and optimized the generation, separation, and migration processes of photoinduced carriers, and (3) the introduction of Cu2+ ions also provided more accessible active sites and more probabilities for the adsorption and activation of CO2 reactants.

TFP5-Mediated CDK5 Activity Inhibition Improves Diabetic Nephropathy via NGF/Sirt1 Regulating Axis.

Diabetic nephropathy (DN) is one of the leading causes of chronic kidney disease (CKD), during which hyperglycemia is composed of the major force for the deterioration to end-stage renal disease (ESRD). However, the underlying mechanism triggering the effect of hyperglycemia on DN is not very clear and the clinically available drug for hyperglycemia-induced DN is in need of urgent development. Here, we found that high glucose (HG) increased the activity of cyclin-dependent kinase 5 (CDK5) dependent on P35/25 and which upregulated the oxidative stress and apoptosis of mouse podocytes (MPC-5). TFP5, a 25-amino acid peptide inhibiting CDK5 activity, decreased the secretion of inflammation cytokines in serum and kidney, and effectively protected the kidney function in db/db mouse from hyperglycemia-induced kidney injuries. In addition, TFP5 treatment decreased HG-induced oxidative stress and cell apoptosis in MPC-5 cells and kidney tissue of db/db mouse. The principal component analysis (PCA) of RNA-seq data showed that MPC-5 cell cultured under HG, was well discriminated from that under low glucose (LG) conditions, indicating the profound influence of HG on the properties of podocytes. Furthermore, we found that HG significantly decreased the level of NGF and Sirt1, both of which correlated with CDK5 activity. Furthermore, knockdown of NGF was correlated with the decreased expression of Sirt1 while NGF overexpression leads to upregulated Sirt1 and decreased oxidative stress and apoptosis in MPC-5 cells, indicating the positive regulation between NGF and Sirt1 in podocytes. Finally, we found that K252a, an inhibitor of NGF treatment could undermine the protective role of TFP5 on hyperglycemia-induced DN in db/db mouse model. In conclusion, the CDK5-NGF/Sirt1 regulating axis may be the novel pathway to prevent DN progression and TFP5 may be a promising compound to improved hyperglycemia induced DN.

Reticulon-1A mediates diabetic kidney disease progression through endoplasmic reticulum-mitochondrial contacts in tubular epithelial cells.

Recent epidemiological studies suggest that some patients with diabetes progress to kidney failure without significant albuminuria and glomerular injury, suggesting a critical role of kidney tubular epithelial cell (TEC) injury in diabetic kidney disease (DKD) progression. However, the major risk factors contributing to TEC injury and progression in DKD remain unclear. We previously showed that expression of endoplasmic reticulum-resident protein Reticulon-1A (RTN1A) increased in human DKD, and the increased RTN1A expression promoted TEC injury through endoplasmic reticulum (ER) stress response. Here, we show that TEC-specific RTN1A overexpression worsened DKD in mice, evidenced by enhanced tubular injury, tubulointerstitial fibrosis, and kidney function decline. But RTN1A overexpression did not exacerbate diabetes-induced glomerular injury or albuminuria. Notably, RTN1A overexpression worsened both ER stress and mitochondrial dysfunction in TECs under diabetic conditions by regulation of ER-mitochondria contacts. Mechanistically, ER-bound RTN1A interacted with mitochondrial hexokinase-1 and the voltage-dependent anion channel-1 (VDAC1), interfering with their association. This disengagement of VDAC1 from hexokinase-1 resulted in activation of apoptotic and inflammasome pathways, leading to TEC injury and loss. Thus, our observations highlight the importance of ER-mitochondrial crosstalk in TEC injury and the salient role of RTN1A-mediated ER-mitochondrial contact regulation in DKD progression.

Relationship between Urinary AD7c-NTP with Cerebral Microbleeds Based on APOE Genotype.

OBJECTIVE: This study was performed to investigate the association between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) with cerebral microbleeds (CMBs) based on the apolipoprotein E (APOE) genotypes. METHODS: A total of 471 patients with acute cerebral infarction screened by magnetic sensitive imaging were enrolled in this study. Among them, twenty-seven cases of mixed CMBs were excluded. A total of 444 patients were divided into two groups according to the presence or absence of CMBs: CMBs group (n = 92) and noncerebral microbleeds group (nCMBs) (n = 352). Urine AD7c-NTP levels were measured using a human enzyme immunoassay kit. RESULTS: In patients with lobar CMBs, there was an interaction between urine AD7c-NTP levels and APOE genotypes (p = 0.01). In patients with APOE ε3/ε3 allele, the odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 0.92 (95% CI: 0.70-1.19). In patients with APOE ε2+ or ε4+ allele, the multivariate-corrected odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 2.95 (95% CI: 1.38-6.27). CONCLUSION: A higher level of urinary AD7c-NTP is involved in lobar CMBs, not deep CMBs.

BPV associated with imaging features of SSI on MRI.

OBJECTIVES: A retrospective study was performed to investigate the relationship between blood pressure variability (BPV) and imaging features of single small infarction (SSI) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Two hundreds and five patients with SSI and 120 healthy subjects matched with age and sex as the control group were enrolled into this study. All subjects came from the Affiliated Hospital to Qingdao University and Qingdao Municipal Hospital from October 2011 to June 2016. Research subjects were classified into different groups. Blood pressure was measured once a day and recorded during the hospitalization period (7-10 days). The followed up data of patients after discharging from hospital was collected from the follow-up records. RESULTS: Twenty-four hours BPV (SBPMean , DSBPMax , DSBPSD , NDBPMax , NDBPSD, and DDBPCV ), day-to-day, and visit-to-visit BPV (SBPMax , SBPSD , DBPMax, and DBPSD ) in the SSI group were significantly higher than that in control group. Compared with the giant lacunar group, day-to-day BPV (SBPMean , SBPMax , SBPSD , SBPCV , DBPMean , DBPMax , DBPSD ), and visit-to-visit BPV (SBPMean , SBPMax , SBPSD , DBPMean , DBPMax , DBPSD ) were significantly higher in the small lacunar infarct group (p < .05). The 24 hr BPV (SBPMean , DDBPMax , DDBPMean ), day-to-day BPV (SBPMax , SBPSD , SBPCV ), and visit-to-visit SBPMax in nonround lesion group were significantly higher than that in round group (p < .05). Compared with nondeep lesion group, some parameters in day-to-day BPV and visit-to-visit BPV were significantly higher in the deep small lesion group (p < .05). CONCLUSION: Increased BPV parameters such as day-to-day and visit-to-visit (SBPMax , SBPSD , DBPMax ) were related to the SSI characterized by small lesion in deep brain region.

Clinical features and risk factors associated with severe COVID-19 patients in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS: The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.

The site pair matching of a tandem Au/CuO-CuO nanocatalyst for promoting the selective electrolysis of CO2 to C2 products.

Tandem catalysis, in which a CO2-to-C2 process is divided into a CO2-to-CO/*CO step and a CO/*CO-to-C2 step, is promising for enhancing the C2 product selectivity when using Cu-based electrochemical CO2 reduction catalysts. In this work, a nanoporous hollow Au/CuO-CuO tandem catalyst was used for catalyzing the eCO2RR, which exhibited a C2 product FE of 52.8% at -1.0 V vs. RHE and a C2 product partial current density of 78.77 mA cm-2 at -1.5 V vs. RHE. In addition, the C2 product FE stably remained at over 40% over a wide potential range, from -1.0 V to -1.5 V. This superior performance was attributed to good matching in terms of the optimal working potential and charge-transfer resistance between CO/*CO-production sites (Au/CuO) and CO/*CO-reduction sites (CuO). This site pair matching effect ensured sufficient supplies of CO/*CO and electrons at CuO sites at the working potentials, thus dramatically enhancing the formation rate of C2 products.

Urinary kynurenine as a biomarker for Parkinson's disease.

OBJECTIVE: To examine whether urine kynurenine (KYN) levels were associated with early-stage Parkinson's disease (PD), as well as the value of urine KYN as a potential biomarker in early-stage PD. METHOD: Eighty-two participants including 41 PD patients and 41 healthy controls were enrolled into this study. Urine KYN levels were measured with a KYN enzyme-linked immunoassay kit. In order to explore the correlation between some clinical parameters and urine KYN, the clinical parameters for these participants were recorded. Diagnostic value and clinical relevance of urine KYN were assessed by using receiver operator characteristic (ROC) curve and correlation analysis. RESULTS: Urine KYN levels were significantly higher in the PD group than in the healthy group (891.95 ± 276.65 pg/ml vs. 640.11 ± 122.37 pg/ml, p = 0.000). The correlations between urine KYN levels and clinical parameters are as follows: Hoehn-Yahr stage (r = 0.676, p = 0.000), disease duration (r = 0.772, p = 0.000), Mini-Mental State Examination scores (r = -0.434, p = 0.005). There was no statistically significant correlation between urine KYN with age, low-density cholesterol (LDL), triglycerides (TG), cholesterol (TC), homocysteine (HCY), uric acid (UA), and glomerular filtration rate (GFR). The ROC analysis showed that urine KYN optimal cutoff value of 751.88 pg/ml had a sensitivity of 65.9% and a specificity of 90.2% for distinguishing between PD and controls, with an area under the curve (AUC) of 0.776. CONCLUSION: Urine KYN were significantly associated with PD severity and mild cognitive impairment. Urine KYN may be a new biomarker for early-stage PD.

Tubular HIPK2 is a key contributor to renal fibrosis.

We previously used global Hipk2-null mice in various models of kidney disease to demonstrate the central role of homeodomain-interacting protein kinase 2 (HIPK2) in renal fibrosis development. However, renal tubular epithelial cell-specific (RTEC-specific) HIPK2 function in renal fibrogenesis has yet to be determined. Here, we show that modulation of tubular HIPK2 expression and activity affects renal fibrosis development in vivo. The loss of HIPK2 expression in RTECs resulted in a marked diminution of renal fibrosis in unilateral ureteral obstruction (UUO) mouse models and HIV-associated nephropathy (HIVAN) mouse models, which was associated with the reduction of Smad3 activation and downstream expression of profibrotic markers. Conversely, WT HIPK2 overexpression in RTECs accentuated the extent of renal fibrosis in the setting of UUO, HIVAN, and folic acid-induced nephropathy in mice. Notably, kinase-dead HIPK2 mutant overexpression or administration of BT173, an allosteric inhibitor of HIPK2-Smad3 interaction, markedly attenuated the renal fibrosis in these mouse models of kidney disease, indicating that HIPK2 requires both the kinase activity and its interaction with Smad3 to promote TGF-ß-mediated renal fibrosis. Together, these results establish an important RTEC-specific role of HIPK2 in kidney fibrosis and further substantiate the inhibition of HIPK2 as a therapeutic approach against renal fibrosis.

Engineering Heterostructured Nanocatalysts for CO2 Transformation Reactions: Advances and Perspectives.

As a conceivable route to achieving anthropological carbon looping, carbon capture and utilization (CCU) technologies employ waste CO2 as an accessible C1 building block to generate upgraded chemicals or fuels, thereby simultaneously remedying environmental issues and energy crises. However, efficient CO2 conversion is disfavored by both its thermodynamics and its kinetics. Heterostructured materials with well-controlled interfaces have great potential for enhanced catalytic performance in various CO2 transformation reactions, owing to the synergistic effects among components, numerous interfacial and/or surface active sites, increased CO2 adsorption capacity, promoted charge transfer efficiency, and unique physicochemical properties. This Review highlights the state of the art in typical heterostructures, such as core-shell, yolk-shell, Janus, hierarchical (branched and hollow), and 2D/2D layered structures, applied for CO2 conversion with various energy inputs (radiation, electricity, heat). Fabrication methods of different heterostructures and structure-composition-performance relationships are also discussed concisely. Finally, a brief summary and prospective research directions are provided. The motivation of this Review is to offer instructive information on the applicability of inorganic heterostructures for CO2 transformation reactions, and it is hoped that further enlightening studies in this field could emerge in the future.

Self-templated synthesis of Co3O4 hierarchical nanosheets from a metal-organic framework for efficient visible-light photocatalytic CO2 reduction.

Efficient photocatalytic conversion of CO2 into energy-rich chemicals is of great significance for both environmental conservation and alleviating the energy crisis. However, convenient synthesis of low-cost, durable and eco-friendly photocatalysts with a novel morphology or structure for highly selective photocatalytic CO2 reduction remains a challenge. Herein, Co3O4 hierarchical nanosheets were synthesized by calcination of novel cobalt metal-organic framework (MOF) nanosheets prepared by a facile oil bath method. In such Co MOF nanosheets, 1,4-naphthalenedicarboxylic acid was chosen as the organic linker, rather than the commonly used 2-methylimidazole for ZIF-67. After thermal treatment in air, the obtained Co3O4 inherited the 2D morphology of its MOF template and evolved into hierarchical nanosheets which were composed of small nanoparticles. Benefiting from the large surface area, abundant mesoporous structure and good capability towards the separation and transfer of photo-generated charge carriers induced by less internal oxygen vacancies, the Co3O4 hierarchical nanosheets showed a CO generation rate of 39.70 µmol h-1 in visible-light photocatalytic CO2 reduction, which was superior to that of Co3O4 nanoparticles and commercial Co3O4. What's more, a CO selectivity of 77.3% was achieved, which is among the highest of cobalt-based spinel oxide photocatalysts for CO2 conversion.

[Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens. RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.

Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study.

This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders.

Acute severe asthma with thyroid crisis and myasthenia: a case report and literature review.

BACKGROUND AND AIMS: Acute severe asthma, thyroid crisis and acute myasthenia are all medical emergencies that rarely coexistent. Here, we report a young man with severe asthma attack, necessitate invasive mechanical ventilation at the onset, followed by thyroid crisis, rhabdomyolysis, acute kidney injury, thrombocytopenia and progressive myasthenia. The aim of this study is to better understand the relationships among severe asthma, autoimmune thyroiditis and myasthenia. METHODS: The case was presented and former literatures were reviewed. RESULTS: This is the first case report of a young patient presented with severe asthma and autoimmune thyroiditis, followed by thyroid storm, multiple organ dysfunction and myasthenia. Neither conventional treatment for asthma or thyroid storm was effective separately. The patient's clinical condition did not improve until after plasmapheresis. CONCLUSION: Here, we highlighted both the importance of early recognition of thyroid storm and prompt therapies, which likely attenuated organ dysfunction and enabled this patient to recover from the life-threatening attack. Asthmatic patients should be closely controlled when suspected of thyroid disorders, especially those with high levels of anti-thyroid antibodies irrespective of thyroid hormones concentrations.

Knockdown of Expression of Cdk5 or p35 (a Cdk5 Activator) Results in Podocyte Apoptosis.

Podocytes are terminally differentiated glomerular epithelial cells. Podocyte loss has been found in many renal diseases. Cdk5 is a cyclin-dependent protein kinase which is predominantly regulated by p35. To study the role of Cdk5/p35 in podocyte survival, we first applied western blotting (WB) analysis to confirm the time-course expression of Cdk5 and p35 during kidney development and in cultured immortalized mouse podocytes. We also demonstrated that p35 plays an important role in promoting podocyte differentiation by overexpression of p35 in podocytes. To deregulate the expression of Cdk5 or p35 in mouse podocytes, we used RNAi and analyzed cell function and apoptosis assaying for podocyte specific marker Wilms Tumor 1 (WT1) and cleaved caspase 3, respectively. We also counted viable cells using cell counting kit-8. We found that depletion of Cdk5 causes decreased expression of WT1 and apoptosis. It is noteworthy, however, that downregulation of p35 reduced Cdk5 activity, but had no effect on cleaved caspase 3 expression. It did, however, reduce expression of WT1, a transcription factor, and produced podocyte dysmorphism. On the other hand increased apoptosis could be detected in p35-deregulated podocytes using the TUNEL analysis and immunofluorescent staining with cleaved caspase3 antibody. Viability of podocytes was decreased in both Cdk5 and p35 knockdown cells. Knocking down Cdk5 or p35 gene by RNAi does not affect the cycline I expression, another Cdk5 activator in podocyes. We conclude that Cdk5 and p35 play a crucial role in maintaining podocyte differentiation and survival, and suggest these proteins as targets for therapeutic intervention in podocyte-damaged kidney diseases.