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.
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.
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.
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
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.
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 electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the ...design of bone microenvironment–specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a β-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca2+/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo. Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration.
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•MXene nanosheets could direct the selective growth of silk nanofibrils.•Prepared MXene/RSF hydrogel exhibited good conductivity and sensing ability.•The electroactive hydrogel could promote osteogenic differentiation of BMSCs by activating the Ca2+/CALM signaling pathway.•The conductive system created an osteoblast–macrophage–endotheliocyte virtuous circle for bone microenvironment.
An efficient iodine‐mediated construction of S−N bond was developed. Such a cross‐dehydrogenative coupling of heterocyclic thiols with amines proceeded smoothly under metal‐free and base‐free ...conditions, and afforded a series of sulfenamides in good to excellent yields. The easily available substrates and convenient synthetic procedure illustrate potential synthetic value of this protocol for the preparation of sulfenamide related biologically or pharmaceutically active compounds.
An iodine‐mediated sulfenamides synthesis was reported. By using iodine as oxidant, various heterocyclic thiols and amines (mainly secondary amines) could smoothly proceed the CDC reaction, affording the target N−S formation products with good yields. The protocol features metal‐free, easy performance, and short reaction time.
The effect of hot-water blanching (HWB) on drying characteristics and product qualities of dried apple slices with the novel integrated freeze-drying (NIFD) process was investigated by comparing with ...3 different FD methods. Compared with the NIFD process without HWB pretreatment (VF-FD), the NIFD process with HWB pretreatment (HWB-VF-FD) resulted in a significantly higher mass loss and more sufficient freezing in vacuum-frozen samples, significantly higher rehydration ratio (RR), higher shrinkage ratio (SR), smaller Vitamin C (VC) content and lower hardness and better apparent shape in freeze-dried samples, and fewer change to the color of the dried or rehydrated samples (p<0.05). Compared with the conventional FD process with HWB pretreatment (HWB-PF-FD), HWB-VF-FD cost significantly less processing time and FD time and obtained significantly higher RR (p<0.05), almost the equivalent SR, VC content, and hardness, and similar appearance in dried samples. The microstructure of apple cell tissues was analyzed by transmission electron microscopy and scanning electron microscopy to interpret the above differences in drying characteristics and product qualities. The results suggested that the NIFD process of apple slices with HWB pretreatment was a promising alternative method to decrease drying time, achieve similar product quality, and simplify the process steps of the conventional FD technology.
Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load ...positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single‐component dual‐functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)‐generated HOCl. A representative prodrug (DHU‐CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU‐CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU‐CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase‐2 (COX‐2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX‐2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU‐CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single‐component dual‐functional prodrug activated by TME‐specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX‐2 inhibitor.
This article presents a single‐component, dual‐functional prodrug, DHU‐CBA2, designed to simultaneously release indomethacin and methylene blue (MB) in response to HOCl. Both in vitro and in vivo studies demonstrate the high sensitivity of DHU‐CBA2 toward HOCl. The prodrug triggers a potent antitumor immune response by combining PDT and cyclooxygenase‐2 inhibition, and exhibits effective antitumor activity.
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