Copper-catalyzed C2-selective alkynylation of chromones via 1,4-conjugate addition.

Copper-catalyzed selective alkynylation with N-propargyl carboxamides as nucleophiles has been successfully developed for the synthesis of C2-functionalized chromanones. Under optimized reaction conditions, 21 examples were obtained in one-pot procedure through 1,4-conjugate addition. This protocol features readily available feedstocks, easy operations, and moderate to good yields, which provides viable access to pharmacologically active C2-functionalized chromanones.

Two new triterpenes from the roots of Pfaffia glomerata.

Pfaffia paniculata is a commercialized dietary supplement used as the substitute for the Asian ginseng in Brazil. We conducted the systematic isolation of the EtOAc fraction with anti-inflammatory effect and two new triterpenoids, along with 26 known compounds were characterized by means of MS and NMR analysis. Interestingly, the new compound 1 is the first seco-ring triterpenoid reported in the Pfaffia genus. Furthermore, among the known compounds, 14 and 15 exhibited anti-inflammatory activity in Caco-2 cells, but two new compounds showed no anti-inflammatory.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Sinomenine inhibits macrophage M1 polarization by downregulating α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1.

BACKGROUND: Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis. In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. PURPOSE: To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. METHODS: The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro, α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. RESULTS: SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. CONCLUSIONS: SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro. The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.

Triterpenoids from Liquidambar Fructus induced cell apoptosis via a PI3K-AKT related signal pathway in SMMC7721 cancer cells.

A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13ß-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 µM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 µM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.

[Effect of total saponins from Panax notoginseng on expession of melatonin receptor mRNA in gastric mucosa of stress rats].

OBJECTIVE: To observe the effect of total saponins from Panax notoginseng (PNS) on melatonin receptor (MR) expression and its content in gastric mucosa of stress rats. METHODS: Water-immersion restraint stress (WRS) was used to induce stress rat models. RevertAid First Strand cDNA Synthesis Kit was used for the reverse transcription of the total RNA from gastric mucosa of stress rats. The PCR product was analyzed by agarose gel electrophoresis firstly and then by KODAK 1 D Image system. The expression level of melatonin 1 (MT1) receptor mRNA was calculated with the optimal density of ratio of MT, receptor and GAPDH. RESULTS: Six hours after WRS, there were 360 bp positive bands in RT-PCR product of MT1. The relative content of MR was lower in the model group than that in the normal group. MR content in PNS group and ranitidine group were both higher than that in the normal group and the model group (P < 0.05 or P < 0.01). CONCLUSION: There is mRNA expression of MT1 receptor in gastric mucosa of stress rats indeed. PNS has protective effect on gastric mucosa of stress rats by up-regulating MR expression, and its protective mechanism may be related to promoting melatonin secretion or increasing the binding capacity of melatonin to its receptor.

[Effect of Kuijieling decoction on proteins expression of IKK-alpha in colonic mucosa of ulcerative colitis model rats].

OBJECTIVE: To explore the changes of protein expression of IKK-alpha as well as the effects of Kuijieling Decoction (KD) on colonic mucosa of ulcerative colitis (UC) model rats. METHODS: UC model rats were induced by TNBS. The rats were randomly divided into six groups: normal control (NC) group, model control (MC) group, Kuijieling low dose (KLD), middle dose (KMD) group, high dose (KHD) group and SASP group. After 10-days' treatment the rats were killed to get their colonic tissues. The positive rate of IKK-alpha expression was detected by immunohistochemical (IHC). RESULTS: The positive rate of IKK-alpha in MC group was significantly higher than that in NC group (P < 0.01). The positive rate of IKK-alpha in KMD group was significantly lower than that in MC group (P < 0.05). The positive rate of IKK-alpha in KHD and SASP group were significantly lower than that in MC group (P < 0.01). CONCLUSION: IKK-alpha may be involved in the pathogenesis of UC, and KD can inhibit positive rate of IKK-alpha in colonic mucosa of UC model rats induced by TNBS. The inhibitory effects of KD on UC may be associated with this.

[Manipulative reduction and percutaneous K-wires fixation for treatment of supracondylar fractures of the humerus in children].

OBJECTIVE: To explore clinical effect of manipulative reduction and percutaneous K-wires fixation in treating supracondylar fractures of the humerus in children. METHODS: From July 2010 to December 2012, clinical data of 52 children with supracondylar fractures of the humerus, which treated with manipulative reduction and percutaneous K-wires fixation, were retrospectively analyzed. Among them, there were 35 males and 17 females with an average age of 6.7 (ranged from 2.5 to 12) years old. All fractures were type Garland II - III fractures, and 51 cases were extension type and 1 case were flexion type. Flynn evaluation standard of elbow performance score were applied to evaluate clinical effects. RESULTS: All patients were followed up from 12 to 18 months with average of 16 months. According to Flynn evaluation standard of elbow performance score, 41 cases obtained excellent result, 8 good and 3 moderate. CONCLUSION: Manipulative reduction and percutaneous K-wires fixation for the treatment of supracondylar fractures of the humerus in children has many advantages, such as minimally invasive, rapid recovery, stable fixation. It could prevent osteofascial compartment syndrome, Volkmann Contracture and cubitus varus.

Vitamin D: preventive and therapeutic potential in Parkinson's disease.

Vitamin D is one of the important nuclear steroid transcription regulators that controls transcriptions of a large number of genes. Vitamin D supplement is commonly recommended for the elderly to prevent bone diseases. Amounting new evidence has indicated that vitamin D plays a crucial role in brain development, brain function regulation and neuroprotection. Parkinson's disease (PD) is a degenerative disorder commonly seen in the elderly, characterized by movement disorders including tremor, akinesia, and loss of postural reflexes. The motor symptoms largely result from the continued death of dopaminergic neurons in the substantia nigra, despite use of current therapeutic interventions. The cause and mechanism of neuron death is currently unknown. Vitamin D deficiency is common in patients with PD suggesting its preventive and therapeutic potential. Vitamin D may exert protective and neurotropic effects directly at cellular level, e.g. protection of dopamine system, and/or by regulating gene expression. This review summarizes the epidemiological, genetic and translational evidence implicating vitamin D as a candidate for prevention and treatment for PD.

[Particle enhanced immunoturbidimetic assay of high sensitive C-reactive protein].

OBJECTIVE: To evaluate the particle enhanced immunoturbidimetic assay of high sensitive C-reactive protein by the automated chemistry analyzer (Hitachi 7170A). METHODS: The detection limit of quantification, measurement range, precision, interference and reference interval were assessed. RESULTS: The measurement range of the method was from 0.125 to 12.5 mg/L. The detection limitation was 0.115 mg/L. The internal and external accuracy were 0.89% and 0.90% respectively. The reference range of the assay was from 0.20 mg/L to 2.60 mg/L. CONCLUSION: The particle enhanced immunoturbidimetic assay is sensitive and stable, and can be used in clinical diagnosis.