Tohoku Journal of Experimental Medicine最新文献

The study investigated the relationship between ratio of D-dimer to brain natriuretic peptide (BNP), large right-to-left shunt (RLS) by contrast-enhanced transthoracic echocardiography (c-TTE), and cryptogenic stroke (CS) in patent foramen ovale (PFO). The study populations were composed of 61 patients with PFO who had been scheduled for transcatheter closure for CS (n = 20) or migraine (n = 41). Large RLS was defined as more than 20 microbubbles at rest and during the Valsalva maneuver by c-TTE. The PFO/CS group exhibited a higher proportion of large RLS at rest (3 vs. 0, P = 0.032) and during the Valsalva maneuver (14 vs. 11, P = 0.002) than the PFO/migraine group. More specifically about PFO characteristics, the height of PFO in the PFO/CS group was higher than that in the PFO/migraine group, and the proportion of atrial septal aneurysm in the PFO/CS group was higher than that in the PFO/migraine group (8 vs. 4, P = 0.013). The ratio of D-dimer to BNP was found to be significantly higher in the PFO/CS group than the PFO/migraine group (P = 0.010). The multiple logistic regression analysis showed that a large RLS during Valsalva maneuver and a high ratio of D-dimer to BNP were independent factors associated with CS in PFO. The study demonstrates that a high ratio of D-dimer to BNP and large RLS by c-TTE as risk factors for CS in PFO.

The purpose of this study was to use bioinformatics techniques to investigate the genetic basis and evaluate medication for individuals with Post-Tuberculosis Tracheobronchial Stenosis (PTTS). Text mining was done to find 63 gene sets that are related to tuberculosis, granulation tissue proliferation, cicatrization, and hypertrophic scars. Using the DAVID and STRING tool to study the functional classification of these genes, revealed that these genes are associated with significant ways for instance the 'MAPK' signaling cascade, 'JAK-STAT' signaling pathway, and the 'VEGF' signaling pathway. The relevance of the genes was suggested by real-time quantitative PCR, which verified that MAPK14, STAT3, and VEGFA expression was elevated in PTTS tissues. The 14 hub genes were used to search the DGI database for drugs associated with these genes and the corresponding diseases. Out of the identified compounds, 34 of them were found to be possible drug candidates that could target PTTS's underlying pathophysiology. Such drugs include those targeting protein kinase, a cytokine with anti-inflammatory properties, angiogenesis inhibitors, and those targeting fibrosis. By applying this bioinformatics workflow, it was possible to use very little time in identifying genes and drugs that are involved in the main disease processes of PTTS. Future work should then be directed to conducting more experimental validation on these genes and possible drug candidates for future therapeutic application.

In December 2019, a novel coronavirus, subsequently named COVID-19, emerged and rapidly propagated both within China and globally. Although the Compound Houttuynia Cordata Mixture (CHM), a traditional Chinese medicine, has shown clinical efficacy in preventing and treating COVID-19, its underlying mechanisms remain inadequately understood. This study evaluates the effectiveness and explores the potential mechanisms of CHM against COVID-19 through the application of network pharmacology, molecular docking, and pseudovirus entry assays. Theoretical analyses based on meridian tropism principles suggest that CHM primarily targets the lung meridian, with additional effects on the heart, stomach, and other organs. An initial review of the TCMSP and STITCH databases identified 103 active components and 205 putative targets, with 69 targets considered therapeutic for COVID-19. Further examination of the GSE152586 dataset, in conjunction with previously identified targets, revealed 16 hub targets potentially critical for CHM's therapeutic effects in vivo. These hub genes are mainly associated with immune responses, inflammation, and cellular responses to external stimuli. Additionally, 59 compounds were identified, including pivotal components such as quercetin, baicalin, and luteolin, which play central roles in the drugs-compounds-targets network. At the cellular level, CHM significantly inhibited the LPS-induced secretion of IL-6 and IL-1β, and curtailed pseudovirus invasion of cells. This comprehensive study elucidates the potential mechanisms and targets of CHM in the prevention of COVID-19, thereby providing a solid foundation for further clinical research.

Hyperuricemia (HUA) is a metabolic disorder caused by purine metabolism. Our study attempts to explore the therapeutic effect of the Fanshi Tongfeng Fang (TFF) formula against HUA and the underlying mechanism. The uric acid (UA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine (Cr) levels were investigated in clinical research and in vivo experiments. The pathologic changes in kidney and xanthine oxidase (XOD) activity were measured by HE staining and kit respectively. The underlying mechanism was predicted by network pharmacology. The mRNA and protein expressions of ABCG2, URAT1, GLUT9, caspase 3, caspase 8, caspase 9, BID, Bax, Bcl-2, JUN, NLRP3, and TNF-α were detected by RT-qPCR assays and western blotting correspondingly.TFF showed a better inhibitory effect on UA, ALT, AST, and Cr levels among HUA patients than urate-lowing therapy and a higher successful treatment ratio. The UA levels, Cr value, and XOD activity were notably down-regulated after TFF treatment in HUA rats, but no measurable difference exists in ALT and AST levels by TFF treatment. Besides, TFF also markedly improved HUA-mediated renal damage and ABCG2 expressions and decreased URAT1 and GLUT9 expressions in HUA rats. Apoptosis and NOD-like receptor signaling pathways were selected according to the network pharmacology. The expressions of caspase 3, caspase 8, caspase 9, BID, Bax, JUN, NLRP3, and TNF-α were significantly decreased by TFF treatment, while Bcl-2 expression was increased by TFF treatment. TFF can alleviate HUA-induced apoptosis and inflammation via the JUN/NLRP3 pathway, which innovatively suggests the therapeutic potential of the TFF formula for HUA treatment.