261 research outputs found
OctaÂcarbonÂyl(5-methÂoxy-2,3-dihydro-1H-benzimidazol-2-yl)di-μ3-sulfido-diiron(I)iron(II)(2 Fe—Fe)
The title compound, [Fe3(C8H8N2O)S2(CO)8], was prepared by the direct reaction of Fe3(CO)12 and 5-methÂoxy-1H-benzoimidazole-2-thiol in tetraÂhydroÂfuran. Desulfurization took place readily to form a sulfide carbonyl cluster. The molÂecule contains a triangle consisting of three Fe atoms capped by two S atoms above and below. There are two Fe—Fe bonds [2.6322 (5) and 2.5582 (5) Å] in the triangle; the length of the third edge [3.3987 (5) Å] is too long to represent an Fe—Fe bond
Performance of a new Candida anti-mannan IgM and IgG assays in the diagnosis of candidemia
Candida is one of the most frequent pathogens of bloodstream infections, which is associated with high morbidity and mortality rates. Rapid immunological detection methods are essential in the early diagnosis of candidemia. Anti-mannan is one of host-derived biomarkers against cell wall components of Candida. We conducted this study to evaluate the diagnostic performance of two anti-mannan assays (IgM, IgG) for candidemia through the analysis of 40 candidemia patients, 48 participants with Candida colonization and 213 participants with neither Candida colonization nor Candida infections (13 patients with other bloodstream infections, 145 hospitalized patients and 55 healthy controls). The performance of the two assays were evaluated by calculating their sensitivity and specificity. The sensitivity ranged from 0.78 to 0.80 for the IgM assay and 0.68 to 0.75 for the IgG assay. The specificity ranged from 0.97 to 0.98 for the IgM assay and 0.91 to 0.94 for the IgG assay. The diagnostic performance of the anti-mannan IgM assay was better than that of IgG, with higher sensitivity and specificity. Combining the two assays (positive results of single or both assays are both considered as positive) could improve the sensitivity up to 0.93 (0.79-0.98) and only slightly reduce the specificity (0.93(0.89-0.95)). The anti-mannan IgM, IgG assays are rapid and cost-effective assays that may be probably useful in the diagnosis of candidemia
Long Non Coding RNA MALAT1 Promotes Tumor Growth and Metastasis by Inducing Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma
The prognosis of advanced oral squamous cell carcinoma (OSCC) patients remains dismal, and a better understanding of the underlying mechanisms is critical for identifying effective targets with therapeutic potential to improve the survival of patients with OSCC. This study aims to clarify the clinical and biological significance of metastasis-associated long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. We found that MALAT1 is overexpressed in OSCC tissues compared to normal oral mucosa by real-time PCR. MALAT1 served as a new prognostic factor in OSCC patients. When knockdown by small interfering RNA (siRNA) in OSCC cell lines TSCCA and Tca8113, MALAT1 was shown to be required for maintaining epithelial-mesenchymal transition (EMT) mediated cell migration and invasion. Western blot and immunofluorescence staining showed that MALAT1 knockdown significantly suppressed N-cadherin and Vimentin expression but induced E-cadherin expression in vitro. Meanwhile, both nucleus and cytoplasm levels of β-catenin and NF-κB were attenuated, while elevated MALAT1 level triggered the expression of β-catenin and NF-κB. More importantly, targeting MALAT1 inhibited TSCCA cell-induced xenograft tumor growth in vivo. Therefore, these findings provide mechanistic insight into the role of MALAT1 in regulating OSCC metastasis, suggesting that MALAT1 is an important prognostic factor and therapeutic target for OSCC
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Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury
Background: Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. Methods: To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to a closed head mild TBI (mTBI) by a standard controlled cortical impact, along with or without treatment of sphingosine 1-phosphate (S1P) or rolipram, after which the brain tissue of the impact site was evaluated for cell morphology via histology, inflammation by qRT-PCR and T cell staining, and cell death with Caspase-3 and TUNEL staining. Circulating lymphocytes were quantified by flow cytometry, and plasma hydrocortisone was analyzed by LC-MS/MS. To investigate the mechanism whereby cortisol lowered the number of peripheral T cells, T cell egress was tracked in lymph nodes by intravital confocal microscopy after hydrocortisone administration. Results: We detected a decreased number of circulating lymphocytes, in particular, T cells soon after mTBI, which was inversely correlated with a transient and robust increase of plasma cortisol. The transient lymphocytopenia might be caused by cortisol in part via a blockade of lymphocyte egress as demonstrated by the ability of cortisol to inhibit T cell egress from the secondary lymphoid tissues. Moreover, exogenous hydrocortisone severely suppressed periphery lymphocytes in uninjured mice, whereas administering an egress-promoting agent S1P normalized circulating T cells in mTBI mice and increased T cells in the injured brain. Likewise, rolipram, a cAMP phosphodiesterase inhibitor, was also able to elevate cAMP levels in T cells in the presence of hydrocortisone in vitro and abrogate the action of cortisol in mTBI mice. The investigation demonstrated that the number of circulating T cells in the early phase of TBI was positively correlated with T cell infiltration and inflammatory responses as well as cell death at the cerebral cortex and hippocampus beneath the impact site. Conclusions: Decreases in intracellular cAMP might be part of the mechanism behind cortisol-mediated blockade of T cell egress. The study argues strongly for a protective role of cortisol-induced immune suppression in the early stage of TBI
Peptidylarginine deiminase 1-catalyzed histone citrullination is essential for early embryo development
Peptidylarginine deiminase (PADI) enzymes are increasingly being associated with the regulation of chromatin structure and gene activity via histone citrullination. As one of the PADI family members, PADI1 has been mainly reported to be expressed in the epidermis and uterus, where the protein in keratinocytes is thought to promote differentiation by citrullinating filament proteins. However, the roles of PADI1 in preimplantation development have not been addressed. Using a PADI1-specific inhibitor and Padi1-morpholino knockdown, we found that citrullination of histone tails at H4R3 and H3R2/8/17 were markedly reduced in the 2- and 4-cell embryos. Consistent with this observation, early embryo development was also arrested at the 4-cell stage upon depletion of PADI1 or inhibition of PADI1 enzyme activity. Additionally, by employing 5-ethynyl uridine (EU) incorporation analysis, ablation of PADI1 function led to a dramatic decrease in overall transcriptional activity, correlating well with the reduced levels of phosphorylation of RNA Pol II at Ser2 observed at 2- or 4-cell stage of embryos under Padi1 knockdown or inhibiting PADI1. Thus, our data reveal a novel function of PADI1 during early embryo development transitions by catalyzing histone tail citrullination, which facilitates early embryo genome transactivation
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Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10
Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study
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A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.
PurposePreaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown.MethodsA rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model.ResultsA novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression.ConclusionOur results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms
Low-level light treatment ameliorates immune thrombocytopenia
Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP
Effect of transcranial direct current stimulation for patients with disorders of consciousness: A systematic review and meta-analysis
IntroductionTranscranial direct current stimulation (tDCS) could potentially facilitate consciousness improvement in patients with disorders of consciousness (DOC). The aim of this study was to investigate the therapeutic efficacy of tDCS on consciousness recovery for patients with DOC.MethodsEight databases were systematically searched from their inception to June 2022. Quality of included studies were assessed using PEDro score and Cochrane’s risk of bias assessment. All statistical analyses were performed using RevMan software. Seventeen studies with 618 patients were identified eligible for this study, and fifteen studies with sufficient data were pooled in the meta-analysis.ResultsThe results of meta-analysis showed a significant effect on increasing GCS scores (MD = 1.73; 95% CI, 1.28–2.18; P < 0.01) and CRS-R scores (MD = 1.28; 95% CI = 0.56–2.00; P < 0.01) in favor of the real stimulation group as compared to sham. The results of subgroup analysis demonstrated that only more than 20 sessions of stimulation could significantly enhance the improvement of GCS scores and the CRS-R scores. Moreover, the effect of tDCS on CRS-R score improvement was predominant in patients with minimal conscious state (MCS) (MD = 1.84; 95% CI = 0.74–2.93; P < 0.01).ConclusionAnodal tDCS with sufficient stimulation doses appears to be an effective approach for patients with MCS, in terms of CRS-R scores.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022336958
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