Traditional Chinese medicine (TCM) has a long history in stroke therapy and its therapeutic efficacy has been confirmed by clinical studies. The molecular basis of the neuroprotective effects is unknown. We wondered whether or not the neuroprotective effect of TCMs might be due to their N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist properties. We used the patch-clamp technique to screen 22 TCM stroke drugs for NMDAR antagonist activity in cultured cortical neurons. The drugs were also screened for their ability to abate NMDA-induced neurotoxicity. Aqueous extracts of Scutellaria baicalensis, Stephania tetrandra, and Salvia miltiorrhiza blocked currents induced by NMDA (200 µM, 10 µM glycine, 0 Mg2+) at a holding potential of –80 mV by 83.45 ± 4.34, 38.65 ± 7.50, and 52.97 ± 1.78%, respectively. The block of the NMDA-evoked currents was voltage-dependent and showed a negative slope conductance reminiscent of Mg2+. Atomic absorption spectrophotometry revealed the presence of 12.5, 2, and 8.7 mM Mg2+ in the extracts of S. baicalensis,S. tetrandra, and S. miltiorrhiza, respectively. None of these extracts blocked NMDA-induced neuronal death. The Uncaria rhynchophylla extract blocked NMDA-evoked currents by 54.98 ± 8.61% even at +60 mV and reduced NMDA-induced neuronal death by 59.13 ± 3.52%. NMDAR antagonist activity may underlie the neuroprotective effects of this TCM. Some TCM drugs may exert therapeutic effects due to their Mg2+ content.
Abstract The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case–control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case–case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group ( P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.
Foreign body (FB) aspiration requiring prompt intervention to prevent severe complications. The endoscopic injection needle, commonly employed for intramucosal injections in the gastrointestinal tract and respiratory tract, while with no previous reports of used for FB extraction. Here we report a case of a pea impacted in the laryngeal ventricle of an adult patient, which became lodged in her right laryngeal ventricle. Conventional methods, such as flexible forceps and baskets, were deemed unsuitable for retrieving this fragile and mushy FB. Therefore, we introduce a novel technique using a modified endoscopic injection needle, which proved successful in removing the foreign body. Laryngoscope , 134:2338–2340, 2024
Abstract Telocytes ( TC s) were identified as a distinct cellular type of the interstitial tissue and defined as cells with extremely long telopodes (Tps). Our previous data demonstrated patterns of mouse TC ‐specific gene profiles on chromosome 1. The present study focuses on the identification of characters and patterns of TC ‐specific or TC ‐dominated gene expression profiles in chromosome 2 and 3, the network of principle genes and potential functional association. We compared gene expression profiles of pulmonary TC s, mesenchymal stem cells, fibroblasts, alveolar type II cells, airway basal cells, proximal airway cells, CD 8 + T cells from bronchial lymph nodes (T‐ BL ), and CD 8 + T cells from lungs (T‐ LL ). We identified that 26 or 80 genes of TC s in chromosome 2 and 13 or 59 genes of TC s up‐ or down‐regulated in chromosome 3, as compared with other cells respectively. Obvious overexpression of Myl9 in chromosome 2 of TC s different from other cells, indicates that biological functions of TC s are mainly associated with tissue/organ injury and ageing, while down‐expression of Pltp implies that TC s may be associated with inhibition or reduction of inflammation in the lung. Dominant overexpression of Sh3glb1, Tm4sf1 or Csf1 in chromosome 3 of TC s is mainly associated with tumour promotion in lung cancer, while most down‐expression of Pde5 may be involved in the development of pulmonary fibrosis and other acute and chronic interstitial lung disease.
Abstract Tumour inflammatory microenvironment is considered to play a role in the sensitivity of tumour cells to therapies and prognosis of patients with lung cancer. The expression of CCL 20, one of the critical chemoattractants responsible for inflammation cells recruitment, has been shown overexpressed in variety of tumours. This study aimed at investigating potential mechanisms of CCL 20 function and production in human non‐small cell lung cancer ( NSCLC ). Expression of CCL 20 gene and protein in lung tissues of patients with NSCLC and NSCLC cells (A549) were determined. The interleukin ( IL )‐1β‐induced signal pathways in A549 and the effect of CCL 20‐induced A549 cell migration and proliferation were determined using migration assays and cell‐alive monitoring system. Mechanisms of signal pathways involved in the migration of CCL 20 were also studied. We initially found that NSCLC tumour tissues markedly overexpressed CCL 20 in comparison with normal lung samples. In addition, IL ‐1β could directly promote CCL 20 production in lung cancer cells, which was inhibited by extracellular signal‐regulated kinase (ERK)1/2 inhibitor, p38 mitogen‐activated protein kinase (p38 MARP) inhibitor or PI 3K inhibitors. CCL 20 promoted lung cancer cells migration and proliferation in an autocrine manner via activation of ERK 1/2‐ MAPK and PI 3K pathways. Our data indicated that IL ‐1β could stimulate CCL 20 production from lung cancer cells through the activation of MAPK s and PI 3K signal pathways, and the auto‐secretion of CCL 20 could promote lung cancer cell migration and proliferation through the activation of ERK and PI 3K signal pathways. Our results may provide a novel evidence that CCL 20 could be a new therapeutic target for lung cancer.
In search of more potent derivatives of sinomenine (1), a clinically available natural alkaloid for the treatment of rheumatoid arthritis (RA), biocatalyzed cross-coupling of sinomenine and guaiacol (2) by Antrodiella semisupina, provided two unique C−C coupled (3 and 4) and one C−O linked (5) novel metabolites. The structures of the metabolites were elucidated by means of MS, 2D NMR techniques and X-ray analysis. 4 exhibited more potent inhibitory activity on IL-6 production than 1 in human synovial sarcoma cell (SW982), and 5 stimulated IL-6 production.
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