Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application.

Astragali Radix (A. Radix) is the dried root of Astragalus membranaceus var. mongholicus (Bge) Hsiao or Astragalus membranaceus (Fisch.) Bge., belonging to the family Leguminosae, which is mainly distributed in China. A. Radix has been consumed as a tonic in China for more than 2000 years because of its medicinal effects of invigorating the spleen and replenishing qi. Currently, more than 400 natural compounds have been isolated and identified from A. Radix, mainly including saponins, flavonoids, phenylpropanoids, alkaloids, and others. Modern pharmacological studies have shown that A. Radix has anti-tumor, anti-inflammatory, immunomodulatory, anti-atherosclerotic, cardioprotective, anti-hypertensive, and anti-aging effects. It has been clinically used in the treatment of tumors, cardiovascular diseases, and cerebrovascular complications associated with diabetes with few side effects and high safety. This paper reviewed the progress of research on its chemical constituents, pharmacological effects, clinical applications, developing applications, and toxicology, which provides a basis for the better development and utilization of A. Radix.

Lightweight Detection Methods for Insulator Self-Explosion Defects.

The accurate and efficient detection of defective insulators is an essential prerequisite for ensuring the safety of the power grid in the new generation of intelligent electrical system inspections. Currently, traditional object detection algorithms for detecting defective insulators in images face issues such as excessive parameter size, low accuracy, and slow detection speed. To address the aforementioned issues, this article proposes an insulator defect detection model based on the lightweight Faster R-CNN (Faster Region-based Convolutional Network) model (Faster R-CNN-tiny). First, the Faster R-CNN model's backbone network is turned into a lightweight version of it by substituting EfficientNet for ResNet (Residual Network), greatly decreasing the model parameters while increasing its detection accuracy. The second step is to employ a feature pyramid to build feature maps with various resolutions for feature fusion, which enables the detection of objects at various scales. In addition, replacing ordinary convolutions in the network model with more efficient depth-wise separable convolutions increases detection speed while slightly reducing network detection accuracy. Transfer learning is introduced, and a training method involving freezing and unfreezing the model is employed to enhance the network's ability to detect small target defects. The proposed model is validated using the insulator self-exploding defect dataset. The experimental results show that Faster R-CNN-tiny significantly outperforms the Faster R-CNN (ResNet) model in terms of mean average precision (mAP), frames per second (FPS), and number of parameters.

Schizophrenia in the genetic era: a review from development history, clinical features and genomic research approaches to insights of susceptibility genes.

Schizophrenia is a devastating neuropsychiatric disorder affecting 1% of the world population and ranks as one of the disorders providing the most severe burden for society. Schizophrenia etiology remains obscure involving multi-risk factors, such as genetic, environmental, nutritional, and developmental factors. Complex interactions of genetic and environmental factors have been implicated in the etiology of schizophrenia. This review provides an overview of the historical origins, pathophysiological mechanisms, diagnosis, clinical symptoms and corresponding treatment of schizophrenia. In addition, as schizophrenia is a polygenic, genetic disorder caused by the combined action of multiple micro-effective genes, we further detail several approaches, such as candidate gene association study (CGAS) and genome-wide association study (GWAS), which are commonly used in schizophrenia genomics studies. A number of GWASs about schizophrenia have been performed with the hope to identify novel, consistent and influential risk genetic factors. Finally, some schizophrenia susceptibility genes have been identified and reported in recent years and their biological functions are also listed. This review may serve as a summary of past research on schizophrenia genomics and susceptibility genes (NRG1, DISC1, RELN, BDNF, MSI2), which may point the way to future schizophrenia genetics research. In addition, depending on the above discovery of susceptibility genes and their exact function, the development and application of antipsychotic drugs will be promoted in the future.

A Review of Extraction and Purification, Biological Properties, Structure-Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis.

Since ancient times, China has used natural medicine as the primary way to combat diseases and has a rich arsenal of natural medicines. With the progress of the times, the extraction of bioactive molecules from natural drugs has become the new development direction for natural medicines. Among the numerous natural drugs, Schisandrin C (Sch C), derived from Schisandra Chinensis (Turcz.) Baill. It has excellent potential for development and has been shown to possess various pharmacological properties, including hepatoprotective, antitumor and anti-inflammatory activities. Based on the biological properties of hepatoprotection, scholars have explored Sch C and its synthetic products in depth; some studies have shown that pentosidine has the effect of improving the symptoms of liver fibrosis and reducing the concentration of alanine transaminase (ALT) and aspartate aminotransferase (AST) in the serum of rats, which is an essential inspiration for the development of anti-liver fibrosis drugs. But more in vivo and ex vivo studies still need to be included. This paper focuses on Sch C's extraction and synthesis, biological activities and drug development progress. The future application prospects of Sch C are discussed to perfect its development work further.

Anti-phospholipid autoantibodies in human diseases.

Anti-phospholipid autoantibodies are a group of antibodies that can specifically bind to anionic phospholipids and phospholipid protein complexes. Recent studies have reported elevated serum anti-phospholipid autoantibody levels in patients with antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis, metabolic disorders, malaria, SARS-CoV-2 infection, obstetric diseases and cardiovascular diseases. However, the underlying mechanisms of anti-phospholipid autoantibodies in disease pathogenesis remain largely unclear. Emerging evidence indicate that anti-phospholipid autoantibodies modulate NETs formation, monocyte activation, blockade of apoptotic cell phagocytosis in macrophages, complement activation, dendritic cell activation and vascular endothelial cell activation. Herein, we provide an update on recent advances in elucidating the effector mechanisms of anti-phospholipid autoantibodies in the pathogenesis of various diseases, which may facilitate the development of potential therapeutic targets for the treatment of anti-phospholipid autoantibody-related disorders.

Two-Electron Oxidations at a Single Cerium Center.

Two-electron oxidations are ubiquitous and play a key role in the synthesis and catalysis. For transition metals and actinides, two-electron oxidation often takes place at a single-metal site. However, redox reactions at rare-earth metals have been limited to one-electron processes due to the lack of accessible oxidation states. Despite recent advancements in nontraditional oxidation state chemistry, the low stability of low-valent compounds and large disparity among different oxidation states prevented the implementation of two-electron processes at a single rare-earth metal center. Here we report two-electron oxidations at a cerium(II) center to yield cerium(IV) terminal oxo and imido complexes. A series of cerium(II-IV) complexes supported by a tripodal tris(amido)arene ligand were synthesized and characterized. Experimental and theoretical studies revealed that the cerium(II) complex is best described as a 4f2 ion stabilized by δ-backdonation to the anchoring arene, while the cerium(IV) oxo and imido complexes exhibit multiple bonding characters. The accomplishment of two-electron oxidations at a single cerium center brings a new facet to molecular rare-earth metal chemistry.

Incomplete Knockdown of MyD88 Inhibits LPS-Induced Lung Injury and Lung Fibrosis in a Mouse Model.

Acute lung injury (ALI) is a life-threatening disorder stemmed mainly from an uncontrolled inflammatory response. Lipopolysaccharide (LPS) is commonly used to induce ALI animal models. Toll-like receptor 4 (TLR4) is the main receptor for LPS, and myeloid differentiation factor 88 (MyD88) is a key adaptor protein molecule in the Toll-like receptor (TLR) signaling pathway. Thus, MyD88 knockdown heterozygous mice (MyD88+/-) were used to investigate the effect of incomplete knockout of the MyD88 gene on indirect LPS-induced ALI through intraperitoneal injection of LPS. The LPS-induced ALI significantly upregulated MyD88 expression, and heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) ameliorated LPS-induced histopathological injury and collagen fiber deposition. Heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) inhibited LPS-induced nuclear factor-κB (NF-κB) pathway activation, but TLR-4 expression tended to be upregulated. Incomplete knockdown of the MyD88 gene also downregulated LPS-induced expression of IL1-ß, IL-6, TNF-α, TGF-ß, SMAD2, and α-SMA. The transcriptome sequencing also revealed significant changes in LPS-regulated genes (such as IL-17 signaling pathway genes) after the incomplete knockdown of MyD88. In conclusion, this paper clarified that LPS activates the downstream NF-κB pathway depending on the MyD88 signaling pathway, which induces the secretion of inflammatory cytokines such as IL-1ß/IL-6/TNF-α and ultimately triggers ALI. Incomplete knockdown of the MyD88 reverses LPS-induced lung fibrosis, which confirmed the vital role of MyD88 in LPS-induced ALI.

Accessing five oxidation states of uranium in a retained ligand framework.

Understanding and exploiting the redox properties of uranium is of great importance because uranium has a wide range of possible oxidation states and holds great potential for small molecule activation and catalysis. However, it remains challenging to stabilise both low and high-valent uranium ions in a preserved ligand environment. Herein we report the synthesis and characterisation of a series of uranium(II-VI) complexes supported by a tripodal tris(amido)arene ligand. In addition, one- or two-electron redox transformations could be achieved with these compounds. Moreover, combined experimental and theoretical studies unveiled that the ambiphilic uranium-arene interactions are the key to balance the stabilisation of low and high-valent uranium, with the anchoring arene acting as a δ acceptor or a π donor. Our results reinforce the design strategy to incorporate metal-arene interactions in stabilising multiple oxidation states, and open up new avenues to explore the redox chemistry of uranium.

[Phenolic derivatives from root bark of Schisandra sphenanthera].

This paper aimed to study the chemical constituents from the root bark of Schisandra sphenanthera. Silica, Sephadex LH-20 and RP-HPLC were used to separate and purify the 80% ethanol extract of S. sphenanthera. Eleven compounds were identified by ~1H-NMR, ~(13)C-NMR, ESI-MS, etc., which were 2-[2-hydroxy-5-(3-hydroxypropyl)-3-methoxyphenyl]-propane-1,3-diol(1), threo-7-methoxyguaiacylglycerol(2),4-O-(2-hydroxy-1-hydroxymethylethyl)-dihydroconiferylalcohol(3), morusin(4), sanggenol A(5), sanggenon I(6), sanggenon N(7), leachianone G(8),(+)-catechin(9), epicatechin(10), and 7,4'-dimethoxyisoflavone(11). Among them, compound 1 was a new compound, and compounds 2-9 were isolated from S. sphenanthera for the first time. Compounds 2-11 were subjected to cell viability assay, and the results revealed that compounds 4 and 5 had potential cytotoxicity, and compound 4 also had potential antiviral activity.

A Combined Synthetic, Magnetic, and Theoretical Study on Enhancing Ligand-Field Axiality for Dy(III) Single-Molecule Magnets Supported by Ferrocene Diamide Ligands.

Molecular design is crucial for improving the performance of single-molecule magnets (SMMs). For dysprosium(III) SMMs, enhancing ligand-field axiality is a well-suited strategy to achieve high-performance SMMs. We synthesized a series of dysprosium(III) complexes, (NNTIPS)DyBr(THF)2 (1, NNTIPS = fc(NSiiPr3)2; fc = 1,1'-ferrocenediyl, THF = tetrahydrofuran), [(NNTIPS)Dy(THF)3][BPh4] (2), (NNTIPS)DyI(THF)2 (3), and [(NNTBS)Dy(THF)3][BPh4] (4, NNTBS = fc(NSitBuMe2)2), supported by ferrocene diamide ligands. X-ray crystallography shows that the rigid ferrocene backbone enforces a nearly axial ligand field with weakly coordinating equatorial ligands. Dysprosium(III) complexes 1-4 all exhibit slow magnetic relaxation under zero fields and possess high effective barriers (Ueff) around 1000 K, comparable to previously reported (NNTBS)DyI(THF)2 (5). We probed the influences of structural variations on SMM behaviors by theoretical calculations and found that the distribution of negative charges defined by rq, i.e., the ratio of the charges on the axial ligands to the charges on the equatorial ligands, plays a decisive role. Moreover, theoretical calculations on a series of model complexes 1'-5' without equatorial ligands unveil that the axial crystal-field parameters B20 are directly proportional to the N-Dy-N angles and support the hypothesis that enhancing the ligand-field axiality could improve SMM performance.

Hederagenin ameliorates renal fibrosis in chronic kidney disease through blocking ISG15 regulated JAK/STAT signaling.

Interstitial fibrosis is the key pathological characteristics of chronic kidney diseases (CKD). In this study, we reported that hederagenin (HDG) can effectively improve the renal interstitial fibrosis and its mechanism. We constructed CKD animal models of ischemia reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) respectively to observe the improvement effect of HDG on CKD. The results showed that HDG can effectively improve the pathological structure of kidney and the renal fibrosis in CKD mice. Meanwhile, HDG can also significantly reduce the expression of α-SMA and FN induced by TGF-ß in Transformed C3H Mouse Kidney-1 (TCMK1) cells. Mechanistically, we performed transcriptome sequencing on UUO kidneys treated with HDG. By real time PCR screening of the sequencing results, we determined that ISG15 plays an important role in the intervention of HDG in CKD. Subsequently, we knocked-down ISG15 in TCMK1 and found that ISG15 knock-down significantly inhibited TGF-ß-induced fibrotic protein expression and JAK/STAT activation. Finally, we performed electrotransfection and used liposomes to transfect ISG15 overexpression plasmids to up-regulate ISG15 in kidney and cells, respectively. We found that ISG15 can aggravate renal tubular cell fibrosis and abolish the protection of HDG on CKD. These results indicated that HDG significantly improves renal fibrosis in CKD by inhibiting ISG15 and its downstream JAK/STAT signaling pathway, which provides a new drug and research target for the subsequent treatment of CKD.

Identification of a novel amphioxus leucine-rich repeat receptor involved in phagocytosis reveals a role for Slit2-N-type LRR in bacterial elimination.

The basal chordate amphioxus is a model for tracing the origin and evolution of vertebrate immunity. To explore the evolution of immunoreceptor signaling pathways, we searched the associated receptors of the amphioxus Branchiostoma belcheri (Bb) homolog of immunoreceptor signaling adaptor protein Grb2. Mass-spectrum analysis of BbGrb2 immunoprecipitates from B. belcheri intestine lysates revealed a folate receptor (FR) domain- and leucine-rich repeat (LRR)-containing protein (FrLRR). Sequence and structural analysis showed that FrLRR is a membrane protein with a predicted curved solenoid structure. The N-terminal Fr domain contains very few folate-binding sites; the following LRR region is a Slit2-type LRR, and a GPI-anchored site was predicted at the C-terminus. RT-PCR analysis showed FrLRR is a transcription-mediated fusion gene of BbFR-like and BbSlit2-N-like genes. Genomic DNA structure analysis implied the B. belcheri FrLRR gene locus and the corresponding locus in Branchiostoma floridae might be generated by exon shuffling of a Slit2-N-like gene into an FR gene. RT-qPCR, immunostaining, and immunoblot results showed that FrLRR was primarily distributed in B. belcheri intestinal tissue. We further demonstrated that FrLRR localized to the cell membrane and lysosomes. Functionally, FrLRR mediated and promoted bacteria-binding and phagocytosis, and FrLRR antibody blocking or Grb2 knockdown inhibited FrLRR-mediated phagocytosis. Interestingly, we found that human Slit2-N (hSlit2-N) also mediated direct bacteria-binding and phagocytosis which was inhibited by Slit2-N antibody blocking or Grb2 knockdown. Together, these results indicate FrLRR and hSlit2-N may function as phagocytotic-receptors to promote phagocytosis through Grb2, implying the Slit2-N-type-LRR-containing proteins play a role in bacterial binding and elimination.

Characterization of Electrospinning Prepared Nitrocellulose (NC)-Ammonium Dinitramide (ADN)-Based Composite Fibers.

Nanoscale composite energetic materials (CEMs) based on oxidizer and fuel have potential advantages in energy adjustment and regulation through oxygen balance (OB) change. The micro- and nanosized fibers based on nano nitrocellulose (NC)-ammonium dinitramide (ADN) were prepared by the electrospinning technique, and the morphology, thermal stability, combustion behaviors, and mechanical sensitivity of the fibers were characterized by means of scanning electron microscope (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), gas pressure measurement of thermostatic decomposition, laser ignition, and sensitivity tests. The results showed that the prepared fibers with fluffy 3D macrostructure were constructed by the overlap of micro/nanofibers with the energetic particles embedded in the NC matrix. The first exothermic peak temperature (Tp) of the samples containing ADN decreased by 10.1 °C at most compared to that of ADN, and the pressure rise time of all the samples containing ADN moved forward compared to that of the sample containing NC only. Furthermore, ADN can decrease the ignition delay time of NC-based fibers under atmosphere at room temperature from 33 ms to 9 ms and can enhance the burning intensity of NC-based fibers under normal pressure. In addition, compared to the single high explosive CL-20 or RDX, the mechanical sensitivities of the composite materials containing high explosive CL-20 or RDX were much decreased. The positive oxygen balance of ADN and the intensive interactions between ADN and NC can reduce the ignition delay time and promote the burning reaction intensity of NC-based composite fibers, while the mechanical sensitivities of composite fibers could be improved.

[Chemical constituents of Helleborus thibetanus].

The chemical constituents of Helleborus thibetanus were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and semi-preparative RP-HPLC, and the structures of all compounds were identified by modern spectrographic technology(MS, NMR). The MTT method was used to measure the cytotoxicity of compounds 1-8. Twelve compounds were isolated from the roots and rhizomes of H. thibetanus and were identified as(25R)-22ß,25-expoxy-26-[(O-ß-D-glucopyranosyl)oxy]-1ß,3ß-dihydroxyfurosta-5-en(1), ß-sitosterol myristate(2), ß-sitosterol lactate(3), ß-sitosterol 3-O-ß-D-glucopyrannoside(4), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(5), 1,3,5-trimethoxybenzene(6), 7,8-dimethylbenzo pteridine-2,4(1H,3H)-dione(7), 1H-indole-3-carboxylic acid(8), p-hydroxy cinnamic acid(9), lauric acid(10), n-butyl α-L-arabinofuranoside(11) and methyl-α-D-fructofuranoside(12), respectively. Among them, compound 1 is a new compound and named thibetanoside L; compounds 2, 5-8, 11 are first isolated from the family Ranunculaceae; compound 12 is isolated from the genus Helleborus for the first time. The results of MTT assay showed that the IC_(50) values of compounds 1-8 against HepG2 and HCT116 cells were greater than 100 µmol·L~(-1).

Aryl hydrocarbon receptor activation drives polymorphonuclear myeloid-derived suppressor cell response and efficiently attenuates experimental Sjögren's syndrome.

Myeloid-derived suppressor cells (MDSCs) comprise heterogeneous myeloid cell populations with immunosuppressive capacity that contribute to immune regulation and tolerance induction. We previously reported impaired MDSC function in patients with primary Sjögren's syndrome (pSS) and mice with experimental SS (ESS). However, the molecular mechanisms underlying MDSC dysfunction remain largely unclear. In this study, we first found that aryl hydrocarbon receptor (AhR) was highly expressed by human and murine polymorphonuclear MDSCs (PMN-MDSCs). Indole-3-propionic acid (IPA), a natural AhR ligand produced from dietary tryptophan, significantly promoted PMN-MDSC differentiation and suppressive function on CD4+ T cells. In contrast, feeding a tryptophan-free diet resulted in a decreased PMN-MDSC response, a phenotype that could be reversed by IPA supplementation. The functional importance of PMN-MDSCs was demonstrated in ESS mice by using a cell-depletion approach. Notably, AhR expression was reduced in PMN-MDSCs during ESS development, while AhR antagonism resulted in exacerbated ESS pathology and dysregulated T effector cells, which could be phenocopied by a tryptophan-free diet. Interferon regulatory factor 4 (IRF4), a repressive transcription factor, was upregulated in PMN-MDSCs during ESS progression. Chromatin immunoprecipitation analysis revealed that IRF4 could bind to the promoter region of AhR, while IRF4 deficiency markedly enhanced AhR-mediated PMN-MDSC responses. Furthermore, dietary supplementation with IPA markedly ameliorated salivary glandular pathology in ESS mice with restored MDSC immunosuppressive function. Together, our results identify a novel function of AhR in modulating the PMN-MDSC response and demonstrate the therapeutic potential of targeting AhR for the treatment of pSS.

A comprehensive review of traditional uses, phytochemistry and pharmacology of Reynoutria genus.

OBJECTIVES: The genus Reynoutria belonging to the family Polygonaceae is widely distributed in the north temperate zone and used in folk medicine. It is administered as a sedative, tonic and digestive, also as a treatment for canities and alopecia. Herein, we reported a review on traditional uses, phytochemistry and pharmacology reported from 1985 up to early 2022. All the information and studies concerning Reynoutria plants were summarized from the library and digital databases (e.g. ScienceDirect, SciFinder, Medline PubMed, Google Scholar, and CNKI). KEY FINDINGS: A total of 185 articles on the genus Reynoutria have been collected. The phytochemical investigations of Reynoutria species revealed the presence of more than 277 chemical components, including stilbenoids, quinones, flavonoids, phenylpropanoids, phospholipids, lactones, phenolics and phenolic acids. Moreover, the compounds isolated from the genus Reynoutria possess a wide spectrum of pharmacology such as anti-atherosclerosis, anti-inflammatory, antioxidative, anticancer, neuroprotective, anti-virus and heart protection. SUMMARY: In this paper, the traditional uses, phytochemistry and pharmacology of genus Reynoutria were reviewed. As a source of traditional folk medicine, the Reynoutria genus have high medicinal value and they are widely used in medicine. Therefore, we hope our review can help genus Reynoutria get better development and utilization.

Optimization of clofibrate with O-desmethyl anetholtrithione lead to a novel hypolipidemia compound with hepatoprotective effect.

Oxidative stress and inflammation were considered to be the major mechanisms in liver damage caused by clofibrate (CF). In order to obtain lipid-lowering drugs with less liver damage, the structure of clofibrate was optimized by O-desmethyl anetholtrithione and got the target compound clofibrate-O-desmethyl anetholtrithione (CF-ATT). CF-ATT significantly reduced the levels of plasma triglycerides (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR-1339. In addition, CF-ATT has a significantly protective effect on the liver compared with CF. The liver weight and liver coefficient were reduced. The hepatic function indexes were also decreased, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Histopathological examination of the liver revealed that inflammatory cell infiltration, nuclear degeneration, cytoplasmic loosening and hepatocyte necrosis were ameliorated by administration with CF-ATT. The hepatoprotective mechanism showed that CF-ATT significantly up-regulated Nrf2 and HO-1 protein expression and down-regulated p-NF-κB P65 expression in the liver. CF-ATT has obviously antioxidant and anti-inflammatory activity. These findings suggested that CF-ATT has significant hypolipidemia activity and exact hepatoprotective effect possibly through the Nrf2/NF-κB-mediated signal pathway.

Effectiveness of Aromatherapy on Ameliorating Fatigue in Adults: A Meta-Analysis.

Background: Fatigue is a common symptom in adults that may cause physical and psychological problems and reduce quality of life. Aromatherapy could possibly provide relief for those suffering from fatigue. Here, we evaluated the effect of aromatherapy on fatigue in adults. Methods: We searched the PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature, SinoMed, Wanfang, and Chinese Scientific Journal Database databases for randomized controlled trials of aromatherapy treatment for fatigue in adults from their inception to June 2021. Two reviewers searched independently, extracted the characteristics of the studies, and assessed the risk of bias using the Cochrane risk-of-bias tool and Stata v. 14.0. Results: Nineteen studies were included in this systematic review. Aromatherapy had a significant effect on fatigue (standardized mean difference -0.64, 95% confidence interval-1.14, -0.15, I2 94.4%, P < 0.001). Subgroup analysis according to aromatic type, substance, frequency, treatment duration, intervention, outcomes measurement, and population type showed that aromatherapy had a significantly greater effect in the intervention group, compared to the control group. Funnel plots and Egger's test indicated no significant publication bias. Conclusion: Our results suggest that aromatherapy ameliorates fatigue in adults who suffer from chronic diseases. A rigorous intervention program and larger randomized controlled trials are needed.

Circ_0044556 Promotes the Progression of Colorectal Cancer via the miR-665-Dependent Expression Regulation of Diaphanous Homolog 1.

BACKGROUND: Cancer progression can be regulated by noncoding circular RNAs. A recent study has indicated that circ_0044556 facilitated the progression of colorectal cancer. AIM: This research was performed to explore the regulatory mechanism of circ_0044556 in CRC. METHODS: Circ_0044556, miR-665 and Diaphanous Homolog 1 levels were detected by the quantitative real-time polymerase chain reaction. Cell proliferation analysis was performed by cell counting kit-8 assay and Edu assay. Cell cycle progression was assessed using flow cytometry. The protein examination was conducted using western blot. Transwell assay was used to analyze cell migration and invasion. Dual-luciferase reporter assay was performed to validate the interaction between targets. In vivo research was implemented by xenograft tumor assay. RESULTS: Circ_0044556 was upregulated in colorectal cancer samples and cells. Silencing circ_0044556 inhibited cell proliferation, cell cycle progression, migration, invasion, and epithelial-mesenchymal transition in CRC cells. Circ_0044556 could directly target miR-665 and the function of circ_0044556 was associated with the regulation of miR-665. In addition, Diaphanous Homolog 1 was a target gene for miR-665 and the anti-tumor role of miR-665 in colorectal cancer was dependent on the downregulation of Diaphanous Homolog 1. Diaphanous Homolog 1 level was regulated by circ_0044556 via sponging miR-665 in CRC cells. In vivo assay suggested that circ_0044556 promoted CRC tumor growth by regulating the miR-665 and Diaphanous Homolog 1 levels. CONCLUSION: Our findings manifested that circ_0044556 functioned as an oncogenic circRNA in colorectal cancer by mediating the miR-665/Diaphanous Homolog 1 axis, elucidating the molecular mechanism of circ_0044556 in CRC progression.

Schisandra sphenanthera: A Comprehensive Review of its Botany, Phytochemistry, Pharmacology, and Clinical Applications.

Schisandra sphenanthera Rehd. et Wils (S. sphenanthera) is a single species of Schisandra genus, Magnoliaceae family, and it is a famous medicinal herb mostly growing in southern China, China Taiwan and Vietnam. S. sphenanthera is usually used for the treatments of hepatitis, Alzheimer's disease, renal transplantation, osteoporosis, and insomnia. In present studies, approximately 310 natural constituents have been isolated from S. sphenanthera, including lignans, triterpenes, volatile oils, and polysaccharides, which were mainly obtained from the fruits and stems of S. sphenanthera. Pharmocological studies have shown that the extracts and monomeric compounds of S. sphenanthera possessed wide-range bioactivities, such as antitumor, anti-oxidant, anti-inflammatory, osteoblastic, immune regulation, neuroprotective, kidney protection, hepatoprotective, and antiviral activities. However, resource availability, quality control measures, in-depth in vivo pharmacological study, and clinical application are still insufficient and deserve further studies. This review systematically summarized literatures on the botany, phytochemistry, pharmacology, development utilization, and clinical application of S. sphenanthera, in hopes of provide a useful reference for researchers for further studies of this plant.