Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function.

Ulcerative colitis (UC) is an idiopathic inflammatory disease mainly affects the large bowel and the rectum. The pathogenesis of this disease has not been fully elucidated, while the disruption of the intestinal barrier function triggered by various stimulating factors related to the host genetics, immunity, gut microbiota, and environment has been considered to be major mechanisms that affect the development of UC. Given the limited effective therapies, the treatment of this disease is not ideal and its incidence and prevalence are increasing. Therefore, developing new therapies with high efficiency and efficacy is important for treating UC. Many recent studies disclosed that numerous herbal decoctions and natural compounds derived from traditional herbal medicine showed promising therapeutic activities in animal models of colitis and have gained increasing attention from scientists in the study of UC. Some of these decoctions and compounds can effectively alleviate colonic inflammation and relieve clinical symptoms in animal models of colitis via regulating intestinal barrier function. While no study is available to review the underlying mechanisms of these potential therapies in regulating the integrity and function of the intestinal barrier. This review aims to summarize the effects of various herbal decoctions or bioactive compounds on the severity of colonic inflammation via various mechanisms, mainly including regulating the production of tight junction proteins, mucins, the composition of gut microbiota and microbial-associated metabolites, the infiltration of inflammatory cells and mediators, and the oxidative stress in the gut. On this basis, we discussed the related regulators and the affected signaling pathways of the mentioned traditional medicine in modulating the disruption or restoration of the intestinal barrier, such as NF-κB/MAPK, PI3K, and HIF-1α signaling pathways. In addition, the possible limitations of current studies and a prospect for future investigation and development of new UC therapies are provided based on our knowledge and current understanding. This review may improve our understanding of the current progression in studies of traditional medicine-derived therapies in protecting the intestinal barrier function and their roles in alleviating animal models of UC. It may be beneficial to the work of researchers in both basic and translational studies of UC.

pH stimulus-disaggregated BODIPY: an activated photodynamic/photothermal sensitizer applicable to tumor ablation.

Herein, we report a pH stimulus-disaggregated BODIPY sensitizer (PTS) with low background-toxicity for achieving activated photodynamic/photothermal tumor therapy. Both the photodynamic and photothermal properties of PTS can be activated under acidic conditions, and PTS exhibits excellent antitumor properties, which is revealed by both in vitro and in vivo tests.

Nitric Oxide-Activated "Dual-Key-One-Lock" Nanoprobe for in Vivo Molecular Imaging and High-Specificity Cancer Therapy.

Cancer treatments are confounded by severe toxic effects toward patients. To address these issues, activatable nanoprobes have been designed for specific imaging and destruction of cancer cells under the stimulation of specific cancer-associated biomarkers. Most activatable nanoprobes were usually activated by some single-factor stimulation, but this restricts therapeutic specificity between diseased and normal tissue; therefore, multifactor activation is highly desired. To this end, we herein develop a novel dual-stimuli responsive theranostic nanoprobe for simultaneously activatable cancer imaging and photothermal therapy under the coactivation of "dual-key" stimulation of "nitric oxide (NO)/acidity", so as to further improve the therapeutic specificity. Specifically, we have integrated a weak electron acceptor (benzo[c][1,2,5]thiadiazole-5,6-diamine) into a donor-π-acceptor-π-donor type chromophore. When the weak acceptor was oxidized by NO in acidic conditions to form a stronger acceptor (5H-[1,2,3]triazolo[4,5-f]-2,1,3-benzothiadiazole), the molecule absorption was significantly increased in the near-infrared region, based on the intramolecular charge transfer (ICT) mechanism. Under the dual-key stimulation of NO/acidity within the tumor associated with inflammation, the nanoprobe can correspondingly output dual signals for ratiometric photoacoustic and photothermal imaging of cancer in vivo and do so with enhanced accuracy and specificity. Our novel nanoprobe exhibited higher photoacoustic signal enhancement under dual-factor activation at 9.8 times that of NO and 132 times that of acidity alone, respectively. Moreover, through such dual activation of NO/acidity, the nanoprobe produces more differentiation of hyperthermia between tumor and normal tissues, to afford satisfactory photothermal therapy with minimal toxic side effects. Thus, our work presents a promising strategy for significantly improving the precision and specificity of cancer imaging and therapy.

Phytic acid attenuates upregulation of GSK-3ß and disturbance of synaptic vesicle recycling in MPTP-induced Parkinson's disease models.

Heightened activity of glycogen synthase kinase-3ß (GSK-3ß) is linked to the degeneration of dopaminergic neurons in Parkinson's disease (PD). Phytic acid (PA), a naturally occurring compound with potent antioxidant property, has been shown to confer neuroprotection on dopaminergic neurons in PD. However, the underlying mechanism remains unclear. In the present study, MPTP and MPP+ treatments were used to model PD in mice and SH-SY5Y cells, respectively. We observed reduced tissue dopamine, disrupted synaptic vesicle recycling, and defective neurotransmitter exocytosis. Furthermore, expression of GSK-3ß was upregulated while that of ß-catenin was downregulated, concentration of cytosolic calcium was increased, and expressions of two dopamine carriers, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were decreased. PA treatment attenuated the MPTP-induced upregulation of GSK-3ß, increase in cytosolic calcium concentration, decreases in the levels of DAT, VMAT2, tissue dopamine, and synaptic vesicle recycling. Importantly, disturbances in synaptic vesicle recycling are thought to be early events in PD pathology. These findings suggest that PA is a promising therapeutic agent to treat early events in PD.

New solvent-stabilized few-layer black phosphorus for antibacterial applications.

Discovering highly efficient, environmentally friendly, and low-cost exfoliating media that can both disperse and protect black phosphorus (BP) remains a challenge. Herein, we demonstrate such a new molecule, N,N'-dimethylpropyleneurea (DMPU), for effective exfoliation and dispersion of two-dimensional BP nanosheets. A very high exfoliation efficiency of up to 16% was achieved in DMPU, significantly surpassing other good solvents. Exfoliated flakes are free from structural disorder or oxidation. Nanosheets retain high stability in DMPU even after addition of 25 vol% of common solvents. The solvation shell appears to protect the nanosheets from reacting with water and air, more remarkably than the best solvent N-cyclohexyl-2-pyrrolidone reported so far. Molecular dynamics simulations of the exfoliation process show that DMPU is among the effective solvents, although energetically it does not appear as favorable as some other amides. We also demonstrate that our exfoliated BP nanosheets exhibit excellent antimicrobial activities against both Escherichia coli and Staphylococcus aureus, outperforming other common two-dimensional materials of graphene and MoS2, suggesting promise in biomedical applications.

Docosahexaenoic acid inhibited the Wnt/ß-catenin pathway and suppressed breast cancer cells in vitro and in vivo.

N-3 fatty acids (FAs) are essential FAs necessary for human health and are known to possess anticancer properties. However, the relationship between n-3 FAs and ß-catenin, one of the key components of the Wnt signaling pathway, in mouse breast cancer remains poorly characterized. In this study, 4T1 mouse breast cancer cells were exposed to a representative n-3 FA, docosahexaenoic acid (DHA), to investigate the relationship between n-3 FAs and the Wnt/ß-catenin signaling pathway in vivo and in vitro. In vitro studies showed that DHA strongly inhibited cell growth, and induced G1 cell cycle arrest both in 4T1 mouse breast cells and MCF-7 human breast cells. DHA reduced ß-catenin expression and T cell factor/lymphoid-enhancing factor reporter activity in 4T1 mouse breast cells. In addition, DHA down-regulated the expression of downstream target genes such as c-myc and cyclinD1. In vivo, therapy experiments were conducted on Babl/c mice bearing breast cancer. We found that feeding mouse the 5% fish oil-supplemented diet for 30 days significantly reduced the growth of 4T1 mouse breast cancer in vivo through inhibition of cancer cell proliferation as well as induction of apoptosis. Feeding animals a 5% fish oil diet significantly induced down-regulation of ß-catenin in tumor tissues with a notable increase in apoptosis. In addition, fish oil-supplemented diet decreased lung metastases of breast cancer. These observations suggested that DHA exerted its anticancer activity through down-regulation of Wnt/ß-catenin signaling. Thus, our data call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of breast cancer.

A framework and its empirical study of automatic diagnosis of traditional Chinese medicine utilizing raw free-text clinical records.

Automatic diagnosis is one of the most important parts in the expert system of traditional Chinese medicine (TCM), and in recent years, it has been studied widely. Most of the previous researches are based on well-structured datasets which are manually collected, structured and normalized by TCM experts. However, the obtained results of the former work could not be directly and effectively applied to clinical practice, because the raw free-text clinical records differ a lot from the well-structured datasets. They are unstructured and are denoted by TCM doctors without the support of authoritative editorial board in their routine diagnostic work. Therefore, in this paper, a novel framework of automatic diagnosis of TCM utilizing raw free-text clinical records for clinical practice is proposed and investigated for the first time. A series of appropriate methods are attempted to tackle several challenges in the framework, and the Naïve Bayes classifier and the Support Vector Machine classifier are employed for TCM automatic diagnosis. The framework is analyzed carefully. Its feasibility is validated through evaluating the performance of each module of the framework and its effectiveness is demonstrated based on the precision, recall and F-Measure of automatic diagnosis results.