The Stimulative Effect of Yangjing Capsule on Testosterone Synthesis through Nur77 Pathway in Leydig Cells

Yangjing Capsule (YC), an innovative Chinese medicine based on traditional prescription, promotes testosterone synthesis by upregulating the expression of steroidogenic enzymes. Nur77 as a nuclear receptor is known to regulate the expression of many steroid synthetases. This study aimed to explore the potential mechanisms by which YC regulates testosterone synthesis in Leydig cells. Real-time PCR and Western blot analysis were employed to assess the expressions of steroidogenic enzymes and Nur77 after treating MLTC-1 cells with YC. The luciferase reporter gene assay was performed to detect the activity of Nur77 gene promoter. Also, the expressions of steroid synthases were detected after Nur77 gene was knocked down. YC significantly stimulated Nur77 production and upregulated StAR and HSD3B expression, and this agrees with the activity of Nur77 gene promoter that was significantly enhanced by YC. Interestingly, knockdown of Nur77 blocked the above YC’s effects and consequently inhibited testosterone synthesis in MLTC-1 cells. YC promotes StAR and HSD3B expression and upregulates testosterone synthesis in Leydig cells, which is mediated by Nur77 pathway

A high interferon gamma signature of CD8+ T cells predicts response to neoadjuvant immunotherapy plus chemotherapy in gastric cancer

BackgroundWhile the tumor microenvironment (TME) affects immune checkpoint blockade (ICB) efficacy, ICB also reshapes the characteristics of TME. Thus far, studies have focused on the TME evolution during neoadjuvant or adjuvant ICB therapy in gastric cancer (GC). However, the interaction between TME characteristics and neoadjuvant immunotherapy plus chemotherapy remains to be elucidated.MethodsWe performed single-cell RNA sequencing on ten GC specimens pre- and post-neoadjuvant camrelizumab plus mFOLFOX6 to determine the impact of the TME on the efficacy of the combination therapy and the remodeling of TME by the therapy.ResultsA high baseline interferon gamma (IFN-γ) signature in CD8+ T cells predicts better responses to the combination therapy. We also observed that the IFN-γ signature significantly decreased in multiple cell types, and the exhausted signature of CD8+ T cells was significantly suppressed during the neoadjuvant therapy.ConclusionsOur data reveal interactions between the TME and neoadjuvant immunotherapy plus chemotherapy in GC. Importantly, it also highlights the signature of CD8+ T cells in predicting response to the combination therapy in GC

Candidate Genes Involved in Tolerance to Fenoxaprop-P-Ethyl in Rice Induced by Isoxadifen-Ethyl Hydrolysate

The metabolic resistance of plants to herbicides is similar to the herbicide metabolism process accelerated by safeners. The tolerance to fenoxaprop-P-ethyl (FE) is distinct among different varieties of rice in which phytotoxicity forms easily, resulting in the restricted use of FE in paddy. Safener effectively resolves this issue. This study showed that rice 9311 and Meixiangzhan No. 2 (MXZ) had different tolerance mechanisms to FE. Isoxadifen-ethyl hydrolysate (IH) alleviated FE the inhibition of rice growth. Transcriptome sequencing revealed numerous differentially expressed genes (DEGs) between the two varieties. A total of 31 metabolic enzyme genes related to herbicide detoxification were screened by analyzing the DEGs in different rice varieties or treatments. The results of the quantitative reverse transcription polymerase chain reaction indicated that 12 genes were potential metabolic genes resistant to FE in rice. Additionally, the enhanced expression of GSTU6, DIMBOA UGT BX8, and ABCG39 was confirmed to be induced by safener. Taken together, our results demonstrated that the induced expression of these three genes might be crucial for resistance to herbicide phytotoxicity in crops. These results may help us to understand herbicide metabolism in crops and to develop novel strategies for the safe use of herbicides

Yangjing Capsule Ameliorates Spermatogenesis in Male Mice Exposed to Cyclophosphamide

Yangjing capsule (YC), a traditional Chinese compound herbal preparation, has been proven as an effective drug to improve spermatogenesis in clinical practice. However, its pharmacological mechanisms were not fully clarified. This study was designed to investigate the protective effects of YC on spermatogenesis in the mouse model of spermatogenesis dysfunction induced by cyclophosphamide (CP). The administration of YC significantly increased the epididymal index, sperm count, and sperm motility of model mice. Histopathological changes demonstrated that CP caused obvious structural damage to testis, which were reversed by the administration of YC. Results from TUNEL assay showed that treatment with YC dramatically decreased the apoptosis of spermatogenic cell induced by CP. Moreover, YC treatment could inhibit the mRNA and protein expression of Bax to Bcl-2 and also raised expression of AR at both mRNA and protein levels. These data suggest that YC might ameliorate spermatogenesis in male mice exposed to CP through inhibiting the apoptosis of spermatogenic cell and enhancing the actions of testosterone in spermatogenesis

La Abeja montañesa : Periódico de intereses locales: Año X Número 2335 - 1866 julio 9

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201