An efficient method for synthesizing thioester compounds under metal‐free conditions was reported. Thus, a series of indole‐substituted thioesters were easily obtained in the presence of PhICl2 ...(dichloroiodo‐benzene) starting from N‐arylthiocarbamates and indoles. This Newman‐Kwart‐type rearrangement reaction features metal free, base free, mild reaction conditions, good functional tolerance, and good yield, showing potential value for preparing some biologically and pharmaceutically active compounds.
In the presence of PhICl2, a series of thioester compounds containing indole structures were obtained starting from indoles and the masked thiols (N‐arylthiocarbamates). This method has the advantage of easily available starting material, metal and base‐free, simple operation, mild reaction conditions, and produces good yields.
Background
The contribution of B‐cell subsets and T‐B cell interaction to the pathogenesis of allergic rhinitis (AR) and mechanisms of allergen immunotherapy (AIT) remain poorly understood. This ...study aimed to outline circulating B‐cell signature, the underlying mechanism, and its association with clinical response to AIT in patients with AR.
Methods
IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies and phenotypes of B cells. Correlations between B cells, T cells, antigen‐specific IgE, and disease severity in AR patients were investigated. Switched memory B cells were co‐cultured with type 2 follicular helper T (Tfh2) cells and follicular regulatory T (Tfr) cells. Associations between B‐cell subsets and clinical benefits of AIT were analyzed.
Results
Frequencies and absolute numbers of circulating memory B cells were increased in AR patients. CD23 expression on CD19+CD20+CD27+IgD− switched memory B cells was significantly enhanced and positively correlated with antigen‐specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in AR patients. Compared with those from healthy controls, Tfh2 cells from AR patients had a greater capacity to induce CD23 expression on switched memory B cells via IL‐4, which was unable to be sufficiently suppressed by AR‐associated Tfr cells with defective IL‐10 expression. CD23 expression on switched memory B cells was downregulated after 12‐month AIT, which positively associated with disease remission in AR patients.
Conclusion
T‐B cell interaction, bridged by CD23 expression particularly on switched memory B cells, may be involved in the disease pathogenesis and mechanism of AIT in patients with AR.
Circulating memory B cells are increased in AR patients. The enhanced expression of CD23 on switched memory B cells correlates with antigen‐specific IgE levels, symptom scores, and allergen immunotherapy efficacy in AR patients. Tfh2 cells from AR patients have a greater capacity to induce CD23 expression on switched memory B cells via IL‐4, which is unable to be sufficiently suppressed by AR‐associated Tfr cells with defective IL‐10 expression.
Abbreviations: AIT, allergen immunotherapy; AR, allergic rhinitis; HC, healthy controls; NSM, nonswitched memory; SM, switched memory; Tfh2, type 2 follicular helper T cells; Tfr, follicular regulatory T cell.
An efficient and practical construction of S−N bond from aryl thioureas and amines under mild and metal‐free conditions is reported. A series of sulfenamides was obtained smoothly from aryl thioureas ...and amines (mainly secondary amines) through cross dehydrogenation coupling reaction (CDC) in the presence of phenyliodine(III) diacetate. The protocol features easily available starting materials, easy and odorless performance, mild reaction conditions, good yields, and a broad substrate scope, illustrating its synthetic value for the synthesis of diverse biologically or pharmaceutically relevant compounds.
A series of sulfenamides was obtained smoothly from aryl thioureas and amines (mainly secondary amines) through cross dehydrogenative coupling reaction (CDC) in the presence of phenyliodine(III) diacetate. The protocol features easily available starting materials, easy and odorless performance, mild reaction conditions, good yields, and a broad substrate scope, illustrating its synthetic value for the synthesis of diverse biologically or pharmaceutically active compounds.
Abstract
A copper‐catalyzed efficient synthesis of alkynyl thioamides starting from tetraalkyl thiuram compounds (TMTM: tetramethyl thiuram monosulfide, TIBTM: tetraisobutyl thiuram monosulfide) and ...alkynes was reported. Thus, tetraalkyl thiurams reacted with alkynes smoothly, giving a variety of alkynyl thioamides promoted by CuI/Cs
2
CO
3
system. This protocol features easy operation, inexpensive starting materials and good yields, illustrating its potential synthetic value for the synthesis of thioamides and their derivatives.
Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As ...interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.
Maslinic acid (MA) could prevent IL‐1β‐associated inflammation as well as extracellular matrix (ECM) degradation in human osteoarthritis (OA) chondrocytes. The potential mechanism involved in the protective effect of MA was that it could reverse inflammation‐related destruction via inhibiting PI3K/AKT/NF‐κB pathways activation. MA ameliorates OA progression in vivo via inhibiting the devastation of cartilage surface, cartilage calcification, and osteophytes formation.
Underpotential deposition offers a predominant way to tailor the electronic structure of the catalytic surface at the atomic level, which is key to engineering materials with a high activity for ...(electro)catalysis. However, it remains challenging to precisely control and directly probe the underpotential deposition of a (sub)monolayer of atoms on nanoparticle surfaces. In this work, we in situ observe silver electrodeposited on gold nanocrystals surface from sub-monolayer to one monolayer by designing a highly sensitive electrochemical dark field scattering setup. The spectral variation is used to reconstruct the optical "cyclic voltammogram" of every single nanocrystal for understanding the underpotential deposition process on nanocrystals, which cannot be achieved by any other methods but are essential for creating novel nanomaterials.
Objective
To analyze the early complications and causes of oblique lateral interbody fusion, and put forward preventive measures.
Methods
There were 235 patients (79 males and 156 females) analyzed ...in our study from October 2014 to May 2017. The average age was 61.9 ± 0.21 years (from 32 to 83 years). Ninety‐one cases were treated with oblique lateral interbody fusion (OLIF) alone (OLIF alone group) and 144 with OLIF combined with posterior pedicle screw fixation through the intermuscular space approach (OLIF combined group). In addition, 137/144 cases in the combined group were primarily treated by posterior pedicle screw fixation, while the treatments were postponed in 7 cases. There were 190 cases of single fusion segments, 11 of 2 segments, 21 of 3 segments, and 13 of 4 segments. Intraoperative and postoperative complications were observed.
Results
Average follow‐up time was 15.6 ± 7.5 months (ranged from 6 to 36 months). Five cases were lost to follow‐up (2 cases from the OLIF alone group and 3 cases from the OLIF combined group). There were 7 cases of vascular injury, 22 cases of endplate damage, 2 cases of vertebral body fracture, 11 cases of nerve injury, 18 cases of cage sedimentation or cage transverse shifting, 3 cases of iliac crest pain, 1 case of right psoas major hematoma, 2 cases of incomplete ileus, 1 case of acute heart failure, 1 case of cerebral infarction, 3 case of left lower abdominal pain, 9 cases of transient psoas weakness, 3 cases of transient quadriceps weakness, and 8 cases of reoperation. The complication incidence was 32.34%. Thirty‐three cases occurred in the OLIF alone group, with a rate of 36.26%, and 43 cases in the group of OLIF combined posterior pedicle screw fixation, with a rate of 29.86%. Fifty‐seven cases occurred in single‐segment fusion, with a rate of 30.0% (57/190), 4 cases occurred in two‐segment fusion, with a rate of 36.36% (4/11), 9 cases occurred in three‐segment fusion, with a rate of 42.86% (9/21), and 6 cases occurred in four‐segment fusion, with a rate of 46.15% (6/13).
Conclusion
In summary, OLIF is a relatively safe and very effective technique for minimally invasive lumbar fusion. Nonetheless, it should be noted that OLIF carries the risk of complications, especially in the early stage of development.
The pathways for Romidepsin-induced apoptosis and cell cycle arrest in HCC cells.
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The aim of the study is to demonstrate the effect of Romidepsin in hepatocellular carcinoma (HCC) by ...inducing G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis through JNK/c-Jun/caspase3 pathway in vitro and in vivo. Human HCC cell lines were cultured with Romidepsin and DMSO (negative control) and 5-fluorouracil (positive control). Then the cells’ viability and apoptosis were determined by cell proliferation assay and flow cytometry. Protein concentrations and expression changes were measured by Western blot. Subsequently, Huh7 cells were subcutaneously inoculated into the nude mice, which were employed to further probe the tumor-suppressive effect of Romidepsin in vivo. Romidepsin treatment led to a time- and dose-dependent induction of cell cycle arrest in the G2/M phase and apoptosis. G2/M phase arrest inhibited the proliferation of HCC cells by alterations in p21/cdc25C/cdc2/cyclinB proteins. Increased concentrations of Erk and JNK phosphorylations were observed in a dose-dependent manner in the Romidepsin group, but p38 phosphorylation was not affected. G2/M phase arrest and the apoptosis of HCC cells induced by Romidepsin were mediated by the activation of Erk/MAPK pathways and JNK/MAPK pathways. The tumor size was significantly larger in the negative control group compared to Romidepsin group and no significant loss in body weight was observed in the Romidepsin group. Our findings offer proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC.
Surface-enhanced Raman scattering (SERS) spectroscopy has attracted tremendous interests as a highly sensitive label-free tool. The local field produced by the excitation of localized surface plasmon ...resonances (LSPRs) dominates the overall enhancement of SERS. Such an electromagnetic enhancement is unfortunately accompanied by a strong modification in the relative intensity of the original Raman spectra, which highly distorts spectral features providing chemical information. Here we propose a robust method to retrieve the fingerprint of intrinsic chemical information from the SERS spectra. The method is established based on the finding that the SERS background originates from the LSPR-modulated photoluminescence, which contains the local field information shared also by SERS. We validate this concept of retrieval of intrinsic fingerprint information in well controlled single metallic nanoantennas of varying aspect ratios. We further demonstrate its unambiguity and generality in more complicated systems of tip-enhanced Raman spectroscopy (TERS) and SERS of silver nanoaggregates.
Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant ...Herba Leonuri, has been shown associated with potent anti‐inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin‐1 beta (IL‐1β) induced over‐production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase‐2, interleukin‐6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose‐dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL‐1β induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL‐1β induced activation of the PI3K/Akt/NF‐κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.
Inhibition of PI3K/Akt/NF‐κB signaling with leonurine for ameliorating the progression of osteoarthritis: in vitro and in vivo studies
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