Viral Load Kinetics of MERS Coronavirus Infection Oh, Myoung-don; Park, Wan Beom; Choe, Pyoeng Gyun ...
New England journal of medicine/The New England journal of medicine,
09/2016, Letnik:
375, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Middle East respiratory syndrome coronavirus continues to circulate in the Middle East. During a recent outbreak in Korea, changes in MERS coronavirus viral load were determined during the course of ...illness in 17 patients.
To the Editor:
The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in South Korea involved 186 patients and resulted in 38 deaths, with four large hospital outbreaks accounting for 82% of the total cases.
1
,
2
Here, we report changes in viral load over time in patients with MERS.
We included all patients who were admitted to three Seoul National University–affiliated hospitals; the institutional review boards of these hospitals approved this study and waived the need for written informed consent on public health grounds. The patients were categorized into a group with severe disease (severe group) or a group . . .
Studies have suggested an increased incidence of acute myocardial infarction (AMI) and ischemic stroke after COVID-19 infection related to an increased risk of thrombosis. Vaccines against SARS-CoV-2 ...are effective against COVID-19 and its progression to severe disease. However, it is unclear if vaccines also prevent secondary complications. Here, Kim et al examined the association between vaccination and AMI and ischemic stroke after COVID-19 infection.
Background Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in ...immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. Study Design Prospective, randomized, controlled, open-label trial. Setting & Participants Septic patients with AKI receiving CVVHDF for AKI. Intervention Conventional (40 mL/kg/h) and high (80 mL/kg/h) doses of CVVHDF for the duration of CRRT. Outcomes Patient and kidney survival at 28 and 90 days, circulating cytokine levels. Results 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P = 0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P = 0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. Limitations Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. Conclusions High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.
Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. ...We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dysregulation of MLL complex-mediated histone methylation plays a pivotal role in gene expression associated with diseases, but little is known about cellular factors modulating MLL complex activity. ...Here, we report that SON, previously known as an RNA splicing factor, controls MLL complex-mediated transcriptional initiation. SON binds to DNA near transcription start sites, interacts with menin, and inhibits MLL complex assembly, resulting in decreased H3K4me3 and transcriptional repression. Importantly, alternatively spliced short isoforms of SON are markedly upregulated in acute myeloid leukemia. The short isoforms compete with full-length SON for chromatin occupancy but lack the menin-binding ability, thereby antagonizing full-length SON function in transcriptional repression while not impairing full-length SON-mediated RNA splicing. Furthermore, overexpression of a short isoform of SON enhances replating potential of hematopoietic progenitors. Our findings define SON as a fine-tuner of the MLL-menin interaction and reveal short SON overexpression as a marker indicating aberrant transcriptional initiation in leukemia.
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•SON negatively controls H3K4me3 and the MLL1/2 complex at transcription start sites•SON interacts with menin and inhibits MLL-menin interaction•Short SON isoforms generated by alternative splicing are upregulated in AML•Short isoforms lacking menin-binding ability attenuate full-length SON function
Kim et al. demonstrate that SON and its splice variants control MLL complex-mediated transcriptional initiation. Full-length SON binds menin and inhibits MLL complex assembly, decreasing H3K4me3. Short, alternatively spliced SON isoforms are upregulated in acute myeloid leukemia and antagonize full-length SON function.
A new, highly conductive (4.1 × 10−4 S cm−1 at 30 °C), highly deformable, and dry‐air‐stable glass 0.4LiI‐0.6Li4SnS4 is prepared using a homogeneous methanol solution. The solution process enables ...the wetting of any exposed surface of the active materials with highly conductive solidified electrolytes (0.4LiI‐0.6Li4SnS4), resulting in considerable improvements in the electrochemical performance of these electrodes over conventional mixture electrodes.
Currently, there are no molecular biomarkers for the early detection of breast cancer. This study focused on identifying surface proteins found on circulating extracellular vesicles (EVs) for ...detecting early-stage breast cancer.
Circulating EVs, isolated from the plasma of 10 patients with breast cancer (stages I and II) and 5 healthy controls, were analyzed using LC-MS/MS. Developmental endothelial locus-1 protein (Del-1) was selected as a candidate biomarker. Two different ELISAs were used to measure Del-1 in plasma samples from healthy controls (n= 81), patients with breast cancer (n= 269), breast cancer patients after surgical resection (n= 50), patients with benign breast tumors (n= 64), and patients with noncancerous diseases (n= 98) in two cohorts.
Plasma Del-1 levels were significantly higher (P< 0.0001) in patients with breast cancer than in all controls and returned to almost normal after tumor removal. The diagnostic accuracy of Del-1 was AUC, 0.961 95% confidence interval (CI), 0.924-0.983, sensitivity of 94.70%, and specificity of 86.36% in test cohort and 0.968 (0.933-0.988), 92.31%, and 86.62% in validation cohort for early-stage breast cancer by one type of ELISA. Furthermore, Del-1 maintained diagnostic accuracy for patients with early-stage breast cancer using the other type of ELISA 0.946 (0.905-0.972), 90.90%, and 77.14% in the test cohort; 0.943 (0.900-0.971), 89.23%, and 80.99% in the validation cohort.
Del-1 on circulating EVs is a promising marker to improve identification of patients with early-stage breast cancer and distinguish breast cancer from benign breast tumors and noncancerous diseases.
Abstract
Background
Toll-like receptor 4 (TLR4) conducts a highly regulated inflammatory process by limiting the extent of inflammation to avoid toxicity and tissue damage, even in bone tissues. ...Thus, it is plausible that strategies for the maintenance of normal bone-immunity to prevent undesirable bone damage by TLR4 activation can exist, but direct evidence is still lacking.
Methods
Osteoclast precursors (OCPs) obtained from
WT
or
Slit3
-deficient mice were differentiated into osteoclast (OC) with macrophage colony-stimulating factor (M-CSF), RANK ligand (RANKL) and lipopolysaccharide (LPS) by determining the number of TRAP-positive multinuclear cells (TRAP
+
MNCs). To determine the alteration of OCPs population, fluorescence-activated cell sorting (FACS) was conducted in bone marrow cells in mice after LPS injection. The severity of bone loss in LPS injected
WT
or
Slit3
-deficient mice was evaluated by micro-CT analysis.
Result
We demonstrate that TLR4 activation by LPS inhibits OC commitment by inducing the concomitant expression of
miR-218–2-3p
and its host gene,
Slit3
, in mouse OCPs. TLR4 activation by LPS induced SLIT3 and its receptor ROBO1 in BMMs, and this SLIT3-ROBO1 axis hinders RANKL-induced OC differentiation by switching the protein levels of C/EBP-β isoforms. A deficiency of SLIT3 resulted in increased RANKL-induced OC differentiation, and the elevated expression of OC marker genes including
Pu.1
,
Nfatc1
, and
Ctsk
. Notably,
Slit3
-deficient mice showed expanded OCP populations in the bone marrow. We also found that miR-218–2 was concomitantly induced with SLIT3 expression after LPS treatment, and that this miRNA directly suppressed
Tnfrsf11a
(RANK) expression at both gene and protein levels, linking it to a decrease in OC differentiation. An endogenous
miR-218–2
block rescued the expression of RANK and subsequent OC formation in LPS-stimulated OCPs. Aligned with these results,
SLIT3
-deficient mice displayed increased OC formation and reduced bone density after LPS challenge.
Conclusion
Our findings suggest that the TLR4-dependent concomitant induction of
Slit3
and
miR-218–2
targets RANK in OCPs to restrain OC commitment, thereby avoiding an uncoordinated loss of bone through inflammatory processes. These observations provide a mechanistic explanation for the role of TLR4 in controlling the commitment phase of OC differentiation.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly affect daily life by causing sleep disturbance due to extreme itching. In addition, if the symptoms of AD are ...severe, it can cause mental disorders such as ADHD and suicidal ideation. Corticosteroid preparations used for general treatment have good effects, but their use is limited due to side effects. Therefore, it is essential to minimize the side effects and study effective treatment methods.
Lindley (DNL) has been widely used for various diseases, but to the best of our knowledge, its effect on AD has not yet been proven. In this study, the inhibitory effect of DNL on AD was confirmed in a DNCB-induced Balb/c mouse. In addition, the inhibitory efficacy of inflammatory cytokines in TNF-α/IFN-γ-induced HaCaT cells and PMACI-induced HMC-1 cells was confirmed. The results demonstrated that DNL decreased IgE, IL-6, IL-4, scratching behavior, SCORAD index, infiltration of mast cells and eosinophils and decreased the thickness of the skin. Additionally, DNL inhibited the expression of cytokines and inhibited the MAPK and NF-κB signaling pathways. This suggests that DNL inhibits cytokine expression, protein signaling pathway, and immune cells, thereby improving AD symptoms in mice.
Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability ...and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.
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