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Due to boron's metalloid properties, aromatic boron reagents are prevalent synthetic intermediates. The direct borylation of aryl C-H bonds for producing aromatic boron compounds offers an appealing, one-step solution. Despite significant advances in this field, achieving regioselective aryl C-H bond borylation using simple and readily available starting materials still remains a challenge. In this work, we attempted to enhance the reactivity of the electron-donor-acceptor (EDA) complex by selecting different bases to replace the organic base (NEt3) used in our previous research. To our delight, when using NH4HCO3 as the base, we have achieved a mild visible-light-mediated aromatic C-H bond borylation reaction with exceptional regioselectivity (rr > 40:1 to single isomers). Compared with our previous borylation methodologies, this protocol provides a more efficient and broader scope for aryl C-H bond borylation through the use of N-Bromosuccinimide. The protocol's good functional-group tolerance and excellent regioselectivity enable the functionalization of a variety of biologically relevant compounds and novel cascade transformations. Mechanistic experiments and theoretical calculations conducted in this study have indicated that, for certain arenes, the aryl C-H bond borylation might proceed through a new reaction mechanism, which involves the formation of a novel transient EDA complex. [ABSTRACT FROM AUTHOR]

Objective. We conducted a systematic review and meta-analysis to evaluate the curative effect of probiotics combined with enteral nutrition (EN) in patients with stroke. Methods. We retrieved randomized controlled trials and case-controlled trials on the use of probiotics for stroke treatment from PubMed, Web of Science, CNKI, Wanfang, and Weipu databases. Retrieval times were from the databases' inception to November 6, 2020. Two researchers conducted a strict evaluation of the literature quality and extracted the data, which were then entered into RevMan 5.3 for meta-analysis. Results. Twenty-three articles were included, including 1,816 patients. The meta-analysis revealed that probiotics combined with EN did not reduce NIHSS scores of patients with stroke (P > 0.05). However, it did shorten hospital stays and bedrest periods (P < 0.05). Probiotics combined with EN also improved patients' nutritional status and increased hemoglobin, albumin, serum total protein, and physical and chemical properties of prealbumin (P < 0.05). In terms of relieving inflammation, we found that probiotics combined with EN reduced neither high-sensitivity C-reactive protein nor procalcitonin (P > 0.05). However, it did cause a significant reduction in TNF-α, IL-6, and IL-10. Probiotics combined with EN significantly reduced esophageal reflux, bloating, constipation, diarrhea, gastric retention, and gastrointestinal bleeding. It relieved intestinal stress and reduced the occurrence of adverse reactions such as esophageal reflux, bloating, constipation, diarrhea, gastric retention, and gastrointestinal bleeding (P < 0.05). In terms of reducing stroke complications, probiotics combined with EN reduced the incidence of lung, gastrointestinal, and urinary tract infections (P < 0.05). It also reduced fatality rates and intestinal flora imbalance rates (P < 0.05). Conclusion. The probiotics combined with EN group's therapeutic effects were superior to those of the EN alone. Thus, probiotics combined with EN is worthy of both clinical application and promotion in stroke treatment. [ABSTRACT FROM AUTHOR]

Objective. We conducted a systematic review and meta-analysis to systematically evaluate the curative effect of Tongqiao Huoxue Decoction (TQHXD) combined with Western medicine treatment (WMT) on Ischemic Stroke (IS). Methods. Randomized controlled trials (RCTs) of TQHXD in the treatment of IS by computer retrieval of PubMed, Embase, Web of Science, Chinese Biomedical Literature Service System, CNKI, Wanfang Database, and Weipu Database. The retrieval time was taken from the establishment of the database to July 30, 2020. Two researchers, respectively, conducted a strict evaluation of the quality of the literature and extracted the data which were then entered in the RevMan5.3 software for meta-analysis. Results. 40 articles were listed, which involved 3260 patients. Meta-analysis results show that TQHXD combined with WMT can significantly reduce patients' NIHSS score, serum hypersensitivity C-reactive protein (hs-CRP), plasma viscosity, serum fibrinogen, serum total cholesterol, and serum triglycerides and improve patients' ADL-Barthel scoring and treatment efficiency. However, there is no evidence that TQHXD combined with the WMT group can significantly decrease the incidence of adverse events. Conclusion. The therapeutic effect of TQHXD combined with the WMT group was significantly better than that of the WMT alone group. For the treatment of patients with IS, TQHXD combined with WMT is worthy of application and promotion. [ABSTRACT FROM AUTHOR]

Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified. [ABSTRACT FROM AUTHOR]

Abstract MicroRNA (miR) is important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to colorectal cancer (CRC). Here, we determined that miR-23a is overexpressed in human colorectal cancer cell lines and tissues compared with that of normal cells. The stable over-expression of miR-23a in CRC cells was sufficient to promote cell proliferation in vitro and in vivo. Further studies showed that miR-23a can directly bind to the 3′untranslated region (3′UTR) of PDK4 mRNA and subsequently repress both the mRNA and protein expressions of PDK4. PDK4 negatively regulate CRC proliferation via suppressing PDH activity. Ectopic expression of PDK4 by transiently transfected with PDK4 vector encoding the entire coding sequence could reverse the effects of miR-23a on CRC proliferation. By this way, miR-23a promotes PDH activation and oxidative phosphorylation to generate sufficient ATP for cell proliferation. Our results illustrated that the up-regulation of miR-23a played an important role in CRC cell proliferation through direct repressing PDK4, suggesting a potential application of miR-23a in prognosis prediction and therapeutic application in CRC. Highlights • miR-23a is overexpressed in CRC cell lines and tissues compared with that of normal cells. • miR-23a repress both the mRNA and protein expressions of PDK4. • PDK4 negatively regulate CRC proliferation via suppressing PDH activity. • miR-23a facilitates PDH activation and oxidative phosphorylation via targeting PDK4. • miR-23a promotes CRC cells proliferation in vitro and in vivo via targeting PDK4. [ABSTRACT FROM AUTHOR]

Drug delivery systems (DDSs) commonly employ arginine–glycine–aspartic acid (RGD) peptides with polyethylene glycol (PEG)-dependent enhanced permeability and retention (EPR) effect to optimise tumour-targeting. However, the PEG dilemma and integrin saturation obstacle are major challenges. To address these issues, we constructed a novel, nano-sized DDS by encapsulating doxorubicin (DOX)-loaded folic acid derivatives of polyamidoamine dendrimer (PAMAM G5.0) in cyclic RGD-tyrosine-lysine pentapeptide (c[RGDyK])-modified liposomes (RGD-SL[FND/DOX]), prepared using thin-film hydration, film-dispersion and hydration-sonication. The liposomes were PEGylated, sterically stabilised and pH-sensitive.In vitro, RGD-SL[FND/DOX] showed pH-sensitive holistic FND/DOX release, and pH-dependent uptake and cytotoxicity in human cancer KB cells. At pH 7.4, RGD-SL[FND/DOX] demonstrated greater cellular uptake and cytotoxicity than relevant control formulations (except FND/DOX) did, although this advantage disappeared at pH 6.5.In vivo, RGD-SL[FND/DOX] inhibited S180 sarcoma xenografted tumour growth in Kunming mice more effectively than FND/DOX did. These findings demonstrate the feasibility of constructing double-stage tumour-targeting nano-sized DDSs such as RGD-SL[FND/DOX]. c[RGDyK] and the EPR effect, facilitated by the particle size (about 110 nm) and PEGylation, helped to target the DDS to the tumour tissue, while the subsequent pH-dependent release of FND/DOX and folic acid-mediated endocytosis specifically targeted the tumour cells, thereby overcoming the PEG dilemma and integrin saturation obstacle. [ABSTRACT FROM AUTHOR]

Investigation on the EtOAc extract of the bark ofZanthoxylum simulansled to the isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2), ( − )-magnolin (3), and ( − )-pinoresinol-di-3,3-dimethylallyl ether (4). Their structures were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR spectra. [ABSTRACT FROM AUTHOR]

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C–H ( 1 – 6 ) bearing an unusual α,β-unsaturated ketone group. The new structures of 1 – 6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1 – 6 showed potent anti-inflammatory activities with IC 50 values ranging from 18.6 to 36.1 μM, and 13.8 to 74.3 μM. [ABSTRACT FROM AUTHOR]