GPR30 selective agonist G-1 induced insulin resistance in ovariectomized mice on high fat diet and its mechanism.

BACKGROUND: Previous in vivo and in vitro studies have demonstrated that estrogen receptor agonist G-1 regulates glucose and lipid metabolism. This study focused on the effects of G-1 on cardiometabolic syndrome and anti-obesity under a high fat diet (HFD). METHODS: Bilateral ovariectomized female mice were fed an HFD for 6 weeks, and treated them with G-1. A cardiomyocyte insulin resistance model was used to simulate the in vivo environment. The main outcome measures were blood glucose, body weight, and serum insulin levels to assess insulin resistance, while cardiac function and degree of fibrosis were assessed by cardiac ultrasound and pathological observations. We also examined the expression of p-AMPK, p-AKT, and GLUT4 in mice hearts and in vitro models to explore the mechanism by which G-1 regulates insulin signaling. RESULTS: G-1 reduced body weight in mice on an HFD, but simultaneously increased blood glucose and promoted insulin resistance, resulting in myocardial damage. This damage included disordered cardiomyocytes, massive accumulation of glycogen, extensive fibrosis of the heart, and thickening of the front and rear walls of the left ventricle. At the molecular level, G-1 enhances gluconeogenesis and promotes glucose production by increasing the activity of pyruvate carboxylase (PC) while inhibiting GLUT4 translocation via the AMPK/TBC1D1 pathway, thereby limiting glucose uptake. CONCLUSION: Despite G-1's the potential efficacy in weight reduction, the concomitant induction of insulin resistance and cardiac impairment in conjunction with an HFD raises significant concerns. Therefore, comprehensive studies of its safety profile and effects under specific conditions are essential prior to clinical use.

ClPIF3-ClHY5 Module Regulates ClPSY1 to Promote Watermelon Fruit Lycopene Accumulation Earlier under Supplementary Red Lighting.

Lycopene content is one of the important factors for determining watermelon fruit quality. In this study, a small-type watermelon was grown in a greenhouse with supplementary red lighting for 10 h per day. The results showed that the content of lycopene in the flesh was increased 6.3-fold after 25 days of supplementary red lighting. qRT-PCR analysis showed that PHYTOENE SYNTHASE 1(ClPSY1) is the major gene that responds to red light within the lycopene synthesis pathway. Moreover, we identified two key transcription factors that were involved in light signal transduction PHYTOCHROME INTERACTING FACTORS 3 (ClPIF3) and LONG HYPOCOTYL 5 (ClHY5) in watermelon flesh. The interaction experiments showed that ClHY5, a potent ClPIF3 antagonist, regulated ClPSY1 expression by directly targeting a common promoter cis-element (G-box). Collectively, our findings identified that ClHY5 and ClPIF3 formed an activation-suppression transcriptional module that is responsive to red light and, through this model, regulated watermelon lycopene accumulation in greenhouse winter cultivation.

Transcription Factor CmWRKY13 Regulates Cucurbitacin B Biosynthesis Leading to Bitterness in Oriental Melon Fruit (Cucumis melo var. Makuwa Makino).

Bitterness, caused by cucurbitacin B (CuB), is one of the important traits that affects melon fruit quality and consumer acceptance. Therefore, the detailed mechanism behind the regulation of CuB biosynthesis on melon fruit needs to be further explored. This study investigated CuB content and transcriptomes of "YMR" melon fruit treated by 5 and 20 mg L-1 CPPU. The content of CuB reaches its peak in 5 days and then decreases. WGCNA identified the WRKY transcription factor (TF), CmWRKY13, coexpressed with CuB biosynthetic genes (Cm180, Cm170, Cm160, and CmACT). Yeast one-hybrid, dual-luciferase, and transient gene expression assays were conducted and suggested that the nucleus-localized CmWRKY13 transactivated the promoters of CuB biosynthetic genes and participated in the regulation of CuB biosynthesis. Furthermore, CmWRKY13 could interact with CmBt, the fruit bitterness-specific TF, which synergistically activated CuB biosynthetic gene expression. These findings provide a novel mechanistic insight for CuB biosynthesis and regulation in melon cultivation.

CmMYB44 might interact with CmAPS2-2 to regulate starch metabolism in oriental melon fruit.

Sugar content is one of the determining factors for melon fruit maturity. Studies have shown that starch gradually degrades during fruit ripening, resulting in sugar accumulation. But the specific relationship between starch metabolism and sucrose accumulation was still unknown. Here, the starch and sugar contents, the activities of key enzymes and the expression patterns of genes related to starch-sucrose metabolism were determined in the fruit of high sugar and starch variety 'HS' and low sugar and starch variety 'LW'. It was found that starch accumulated during fruit development process, and then degraded at 30 days after anthesis (DAA), which was synchronized with sucrose accumulation in 'HS' fruit, while starch and sucrose contents were always at a lower level during 'LW' fruit maturation. Furthermore, starch metabolism-related enzymes (Adenine dinucleotide phosphate -glucose pyrophosphorylase (AGPase), α-amylase (AMY), ß-amylase (BMY)) and the key enzymes for sucrose accumulation (sucrose phosphate synthase (SPS) and sucrose synthase (SS)) were significantly increased at ripening stage of 'HS' fruit, and their activities were consistent with the expressions of CmAPS2-2, CmAMY2, CmBAM1, CmBAM9 and CmSPS1. However, the contents of starch and sucrose and the activities of AGPase and SPS in 'LW' fruit didn't change significantly. We discovered an R2R3-type MYB transcription factor, CmMYB44, screened from yeast one hybrid library, could directly bind to the promoter of CmAPS2-2 to inhibit its transcription. These results revealed that the targeted down-regulation of CmAPS2-2 by CmMYB44 might be involved in the starch accumulation process, which affect the flavor quality of oriental melon fruit.

Percutaneous intratumoral injection with pingyangmycin lipiodol emulsion for the treatment of recurrent sacrococcygeal chordomas.

This study describes fluoroscopy-guided percutaneous intratumoral injection therapy (PIIT) with a pingyangmycin lipiodol emulsion in the management of recurrent sacrococcygeal chordomas after surgical excision. Seven patients underwent a total of 22 treatment sessions (3-4 sessions per patient); treatment responses were evaluated clinically, and lesion size was determined using computed tomography (CT). Over 10-26 months of follow-up, tumor sizes and visual analogue scale (VAS) scores of all patients were decreased. No patients had complications during the follow-up period. Preliminary results showed that PIIT with pingyangmycin lipiodol emulsion under fluoroscopic guidance is effective and safe and may be considered as a treatment option.

[Percutaneous intratumoral injection with pingyangmycin lipiodol emulsion for treatment of recurrent sacrococcygeal chordomas].

OBJECTIVE: To evaluate the effectiveness and safety of fluoroscopy-guided percutaneous intratumor injection of pingyangmycin lipiodol emulsion (PLE) in the management of recurrent sacrococcygeal chordomas. METHODS: Seven patients with recurrent sacrococcygeal chordomas presenting with severe local pain with visual analogue score (VAS)≥8 received treatment sessions of fluoroscopy-guided percutaneous intratumor injection of PLE. The patients were followed up every 3 months after the last session to assess their clinical responses and observe the changes in the tumor size measured by computed tomography. The changes in the VAS, tumor necrosis and pain relief as well as the adverse events were recorded. RESULTS: A total of 22 sessions of fluoroscopy-guided percutaneous intratumoral PLE injection was performed in these cases (3 or 4 sessions in each case). The total average pingyangmycin dose delivered was 48.0 mg and the average lipiodol dose was 40.0 ml in each case. Five patients showed low fever and vomiting 48 after the injection. During the follow-up (median time of 21.7 months, range 10-26 months), all the patients showed obviously reduced tumor size and VAS, and partial remission was achieved in 6 patients and stable disease (SD) in 1 patient. None of the patients had complications during the follow-up. CONCLUSION: Fluoroscopy-guided percutaneous intratumoral injection of PLE can be effective and safe and may serve as a alternative for treatment of recurrent sacrococcygeal chordomas.