A Randomized Phase II Efficacy, Activity and Safety Study of GLQ223 Alone and in Combination With Zidovudine in Symptomatic HIV-Infected Patients Without Prior Treatment With GLQ223 or Trichosanthin

This study involves GLQ223 administration to patients who have not previously been exposed to it, but who have received at least 9 months of zidovudine therapy. Efficacy evaluations will include survival, opportunistic infections, T4 cell count, and assessments of viral load.

开始日期-

申办/合作机构

Genelabs Technologies, Inc.

100 项与 Trichosanthin 相关的临床结果

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100 项与 Trichosanthin 相关的转化医学

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100 项与 Trichosanthin 相关的专利（医药）

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328

项与 Trichosanthin 相关的文献（医药）

2024-11-01·Journal of Advanced Research

Trichosanthin elicits antitumor activity via MICU3 mediated mitochondria calcium influx

Article

作者: Lu, Liming ; Chen, Hongzhuan ; Zhang, Yunbin ; Ding, Xuping ; Zhang, Qian ; Zeng, Cong

INTRODUCTIONTrichosanthin (TK) is a glycoprotein extracted from the Chinese medicinal herb Trichosanthes kirilowi, which has anti-virus and anti-tumor activity. However, the target and detailed mechanism of TK remains elusive.OBJECTIVESWe aimed to identify novel antitumor targets of TK in lung adenocarcinoma and study its anti-tumor mechanism.METHODSWe utilized a Lewis lung carcinoma mouse model to evaluate the inhibition of TK on tumor growth. CCK8 assay was utilized to calculate IC₅₀ of trichosanthin on A549 and H1299. In-vitro cellular assays and in-vivo xenograft mice studies were used to investigate MICU3 overexpression and TK treatment on tumor growth. Fluo-4 dye and JC-1 staining was used to measure the mitochondrial calcium levels and membrane potential. H&E and immunohistochemistry staining were applied the asses the effect of TK on tumor and microenvironment. RNA sequencing was applied to analyze transcriptome changes in TK-treated and MICU3-overexpressed tumor cells. The influence of trichosanthin on DNMT3B expression and MICU3 methylation were detected by qPCR and Western blotting. Transcriptional activity of the MICU3 gene was measured by ChIP-PCR and luciferase assays.RESULTSTrichosanthin ihibited the tumor growth in vivo, resulting cancer cell growth inhibition and cell death, with almost no effect on normal cells. IC₅₀ of trichosanthin in A549 and H1299 cells were 62.8 μg/ml and 39.7 μg/ml, respectively. Mitochondrial Calcium Uptake Family complex MICU3 was shown to associated with favorable prognosis and was upregulated upon trichosanthin treatment, along with reduces tumor cell growth and migration, and increased cell death both in vitro and in vivo. Increased mitochondrial calcium level was observed in MICU3 overexpression cells. Pathway analysis of RNA-seq data revealed that cytokine and receptor pathways were enriched in MICU3-overexpressing cells. Trichosanthin decreased DNMT3B expression and altered MICU3 methylation while increased FOSL2 expression and reduced methylation that correlated with increased transcription of the MICU3 gene.CONCLUSIONTrichosanthin elicits antitumor activity in lung adenocarcinoma via repressing DNMT3B and increasing FOSL2, which in turn induces MICU3-mediated mitochondrial calcium influx and tumor cell death.

2024-03-04·Revista medica del Instituto Mexicano del Seguro Social

Nuevo tratamiento para colesterol HDL con Trichosanthin A y metformina en prediabetes: ensayo clínico controlado

Article

作者: Covarrubias-Cortés, Alejandro ; Martínez-Castañeda, Diana ; Jácome-Mondragón, José Antonio ; López-Ríos, Sandra ; Rojas-Jiménez, José Alberto ; Velázquez-Hernández, Blanca ; Moreno-Vázquez, Nancy ; Mota-Sanhua, Vanessa

BackgroundIn adults with prediabetes, it is estimated that 51.2% have atherogenic dyslipidemia with low HDL cholesterol, not always diagnosed or treated. The present study evaluates a new intervention adding a class I-II histone deacetylase inhibitor (Trichosanthin A) to the standard management of metformin to treat prediabetes and increase HDL cholesterol.ObjectiveTo evaluate the efficacy of Trichosanthin A and prolonged release metformin on the increase in HDL cholesterol in women with prediabetes.Material and methodsDouble-blind randomized controlled trial with lifestyle management. Group 1 with histone I-II deacetylase inhibitor (Trichosanthin A) and extended-release metformin; group 2 with extended-release metformin and group 3 with placebo. The outcome variable HDL cholesterol evaluated at baseline and after 12 weeks. The study included women between 20-65 y.o., body mass index 25.0-34.9 with prediabetes.ResultsThe study sample was made up of 104 female patients, average age of 46 years (SD+8.6), average body mass index of 30.9 (SD + 4.14). In the Trichosanthin A and extended-release metformin group, an increase on HDL cholesterol was observed (2.92 mg/dL; p = 0.027).ConclusionsThe histone I-II deacetylase inhibitor (Trichosanthin A) in addition to standard intensive lifestyle treatment and extended-release metformin significantly increases HDL cholesterol.

2024-01-01·Heliyon

Trichosanthin alleviates streptozotocin-induced type 1 diabetes mellitus in mice by regulating the balance between bone marrow-derived IL6+ and IL10+ MDSCs

Article

作者: Wang, Kefan ; Lu, Liming ; Sun, Hanxiao ; Qiu, Ju ; Huang, Biao ; Sheng, Huiming ; Ding, Xuping ; Liu, Yuting ; Wu, Jiaoxiang ; Shu, Jie ; Zhang, Jie

Myeloid-derived suppressor cells (MDSCs) occupy a pivotal role in the intricate pathogenesis of the autoimmune disorder, Type 1 diabetes mellitus (T1DM). Since our previous work demonstrated that trichosanthin (TCS), an active compound of Chinese herb medicine Tian Hua Fen, regulated immune response, we aimed to clarify the efficacy and molecular mechanism of TCS in the treatment of T1DM. To this end, T1DM mouse model was established by streptozotocin (STZ) induction. The mice were randomly divided into normal control group (Ctl), T1DM group (STZ), TCS treated diabetic group (STZ + TCS) and insulin-treated diabetic group (STZ + insulin). Our comprehensive evaluation encompassed variables such as blood glucose, glycosylated hemoglobin, body weight, pertinent biochemical markers, pancreatic histopathology, and the distribution of immune cell populations. Furthermore, we meticulously isolated MDSCs from the bone marrow of T1DM mice, probing into the expressions of genes pertaining to the advanced glycation end product receptor (RAGE)/NF-κB signaling pathway through RT-qPCR. Evidently, TCS exhibited a substantial capacity to effectively counteract the T1DM-induced elevation in random blood glucose, glycosylated hemoglobin, and IL-6 levels in plasma. Pathological scrutiny underscored the ability of TCS to mitigate the damage incurred by islets. Intriguingly, TCS interventions engendered a reduction in the proportion of MDSCs within the bone marrow, particularly within the IL-6⁺ MDSC subset. In contrast, IL-10⁺ MDSCs exhibited an elevation following TCS treatment. Moreover, we observed a significant down-regulation of relative mRNA of pro-inflammatory genes, including arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), RAGE and NF-κB, within MDSCs due to the influence of TCS. It decreases total MDSCs and regulates the balance between IL-6⁺ and IL-10⁺ MDSCs thus alleviating the symptoms of T1DM. TCS also down-regulates the RAGE/NF-κB signaling pathway, making it a promising alternative therapeutic treatment for T1DM. Collectively, our study offered novel insights into the underlying mechanism by which TCS serves as a promising therapeutic intervention for T1DM.

100 项与 Trichosanthin 相关的药物交易

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