Gypenoside L inhibits hepatocellular carcinoma by targeting the SREBP2-HMGCS1 axis and enhancing immune response.

Hepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver, with a high degree of malignancy and relatively poor prognosis. Gypenoside L has inhibitory effects on liver cancer cells. However, its mechanism of action is still unclear. This study aims to investigate the inhibitory effects of gypenoside L on HCC in vitro and in vivo, and explore its potential mechanisms. The results showed that gypenoside L reduced the cholesterol and triglyceride content in HepG2 and Huh-7 cells, inhibited cell proliferation, invasion and metastasis, arrested cell cycle at G0/G1 phase, promoted cell apoptosis. Mechanistically, it targeted the transcription factor SREPB2 to inhibit the expression of HMGCS1 protein and inhibited the downstream proteins HMGCR and MVK, thereby regulating the mevalonate (MVA) pathway. Overexpression HMGCS1 led to significant alterations in the cholesterol metabolism pathway of HCC, which mediated HCC cell proliferation and conferred resistance to the therapeutic effect of gypenoside L. In vivo, gypenoside L effectively suppressed HCC growth in tumor-bearing mice by reducing cholesterol production, exhibiting favorable safety profiles and minimal toxic side effects. Gypenoside L modulated cholesterol homeostasis, enhanced expression of inflammatory factors by regulating MHC I pathway-related proteins to augment anticancer immune responses. Clinical samples from HCC patients also exhibited high expression levels of MVA pathway-related genes in tumor tissues. These findings highlight gypenoside L as a promising agent for targeting cholesterol metabolism in HCC while emphasizing the effectiveness of regulating the SREBP2-HMGCS1 axis as a therapeutic strategy.

Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs.

Background: It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods: Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results: Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13-27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions: Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.

Gypenosides suppress hepatocellular carcinoma cells by blocking cholesterol biosynthesis through inhibition of MVA pathway enzyme HMGCS1.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality. Targeting abnormal cholesterol metabolism is a potential therapeutic direction. Therefore, more natural drugs targeting cholesterol in HCC need to be developed. Gypenosides (Gyp), the major constituent of Gynostemma pentaphyllum, has been demonstrated to have pharmacological properties on anti-cancer, anti-obesity, and hepatoprotective. We investigated whether Gyp, isolated and purified by our lab, could inhibit HCC progression by inhibiting cholesterol synthesis. The present research showed that Gyp inhibited proliferation and migration, and induced apoptosis in Huh-7 and Hep3B cells. Metabolomics, transcriptomics, and target prediction all suggested that lipid metabolism and cholesterol biosynthesis were the mechanisms of Gyp. Gyp could limit the production of cholesterol and target HMGCS1, the cholesterol synthesis-related protein. Downregulation of HMGCS1 could suppress the progression and abnormal cholesterol metabolism of HCC. In terms of mechanism, Gyp suppressed mevalonate (MVA) pathway mediated cholesterol synthesis by inhibiting HMGCS1 transcription factor SREBP2. And the high expression of HMGCS1 in HCC human specimens was correlated with poor clinical prognosis. The data suggested that Gyp could be a promising cholesterol-lowering drug for the prevention and treatment of HCC. And targeting SREBP2-HMGCS1 axis in MVA pathway might be an effective HCC therapeutic strategy.

Protective effect of heat-processed Gynostemma pentaphyllum on high fat diet-induced glucose metabolic disorders mice.

Glucose metabolic disorders (GMD) can promote insulin resistance (IR) and diabetes, and damage liver and kidney. Gynostemma pentaphyllum is commonly used in the clinical treatment of diabetes, but the research on its main active constituents and GMD has not been reported yet. This study explores the therapeutic potential of gypenosides of heat-processed Gynostemma pentaphyllum (HGyp) on high-fat diet-induced GMD in mice. HGyp was administered at different doses for 12 weeks. The investigation encompassed an array of parameters, including body weight, blood lipids, blood glucose, and liver tissue components. Metabolomic and network analyses were conducted to uncover potential targets and pathways associated with HGyp treatment. The results revealed that HGyp alleviated GMD by reducing body weight, blood glucose, and improving blood lipids levels, while increasing liver glycogen and antioxidant enzyme levels. Additionally, HGyp exhibited protective effects on liver and kidney health by reducing tissue damage. Fourteen blood components were detected by LC-MS. Metabolomic and network analyses indicated the potential engagement of the AGE-RAGE signaling pathway in the therapeutic effects of HGyp.Furthermore, Western blot and ELISA assays confirmed that HGyp upregulated GLO1 and GLUT4 while down-regulating AGEs and RAGE expression in liver tissue. In light of these findings, HGyp demonstrates promise as a potential therapeutic candidate for combating GMD, warranting further exploration in the development of therapeutic strategies or functional products.

Anatomical study of the ideal cortical bone trajectory in the lumbar spine.

BACKGROUND: To explore the ideal trajectory of lumbar cortical bone trajectory screws and provide the optimal placement scheme in clinical applications. METHODS: Lumbar computed tomography (CT) data of 40 patients in our hospital were selected, and the cortical vertebral bone contour model was reconstructed in three dimensions (3D). Depending on the different regions of the screw through the entrance and exit of the pedicle, 9 trajectories were obtained through combinational design: T-Aa, T-Ab, T-Ac, T-Ba, T-Bb, T-Bc, T-Ca, T-Cb, and T-Cc. Cortical bone trajectory (CBT) screws with appropriate diameters were selected to simulate screw placement and measure the parameters corresponding to each trajectory (screw path diameter, screw trajectory length, cephalad angle, and lateral angle), and then determine the optimal screw according to the screw parameters and screw safety. Then, 23 patients in our hospital were selected, and the navigation template was designed based on the ideal trajectory before operation, CBT screws were placed during the operation to further verify the safety and feasibility of the ideal trajectory. RESULTS: T-Bc and T-Bb are the ideal screw trajectories for L1-L2 and L3-L5, respectively. The screw placement point is located at the intersection of the inner 1/3 vertical line of the superior facet joint and the bottom 1/3 horizontal line of the outer crest of the vertebral lamina (i.e., 2-4 mm inward at the bottom 1/3 of the outer crest of the vertebral lamina). CBT screws were successfully placed based on the ideal screw trajectory in clinical practice. During the operation or the follow-up period, there were no adverse events. CONCLUSION: CBT screw placement based on the ideal screw trajectory is a safe and reliable method for achieving effective fixation and satisfactory postoperative effects.

Feasibility of cortical bone trajectory screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration.

BACKGROUND: To investigate the feasibility of using cortical bone trajectory (CBT) screws for bridging fixation in revision surgery for lumbar adjacent segment degeneration and to provide a reference for clinical practice. METHODS: Computed tomography scans of the lumbar spines of 36 patients in our hospital were used. Sixteen males and 20 females with an average age of 65.5 ±â€Š10.5 years (range: 46 to 83 years) were included. Three-dimensional reconstruction was performed using computer software. Screws with appropriate sizes were selected for the L1 to L5 vertebral segments, and traditional pedicle screws were placed using the standard method. After completing screw placement, simulated placement of CBT screws was performed separately. No overlap occurred between the two screws in the process of CBT screw placement, and the placement point and direction were adjusted until screw placement completion. After all screw placement simulations were complete, according to the contact area of the cortical bone of the screw trajectory and the screw puncture position and distance through the trajectory, the screw placement results were categorized as excellent, good, general, and failure. Excellent and good ratings were considered successful, while a general rating was regarded as acceptable. Then, the success rate and acceptable rate of each segment of the lumbar spine were calculated. RESULTS: Three hundred and sixty screw placement simulations were performed in lumbar pedicles, and 72 CBT screws were implanted in each vertebral body of the lumbar spine. The success rates in the L1 to L5 segments were 73.6%, 80.6%, 83.3%, 88.9%, and 77.8%, respectively, and the acceptable rates were 91.7%, 97.2%, 97.2%, 100%, and 91.7%, respectively. The overall success rate and acceptable rate of CBT screw placement in the lumbar spine were 80.8% and 95.6%, respectively. CONCLUSION: CBT screws are feasible for bridging fixation in lumbar adjacent segment degeneration revision surgery, and the accuracy of screw placement in different lumbar vertebrae varies.