Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Research progress in the treatment of schistosomiasis with traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice. AIM OF THE STUDY: To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis. MATERIALS AND METHODS: In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China. RESULTS: In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy. CONCLUSION: Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.

Use of a large-bore 088 intracranial access support catheter for delivery of large intracranial devices: case series with the TracStar LDP in 125 cases.

BACKGROUND: The delivery of neuroendovascular devices requires a robust proximal access platform. This demand has previously been met with a 6Fr long sheath (8Fr guide) that is placed in the proximal internal carotid artery (ICA) or vertebral artery segments. We share our experience with the first 0.088 inch 8Fr guide catheter designed for direct intracranial access. METHODS: We retrospectively reviewed a prospectively maintained IRB-approved institutional database of the senior authors to identify all cases where the TracStar Large Distal Platform (LDP) was positioned within the intracranial vasculature, defined as within or distal to the petrous ICA, vertebral artery (V3) segments, or transverse sinus. Technical success was defined as safe placement of the TracStar LDP within or distal to the described distal vessel segments with subsequent complication-free device implantation. RESULTS: Over the 41-month study period from January 2020 to June 2023, 125 consecutive cases were identified in whom the TracStar LDP was navigated into the intracranial vasculature for triaxial delivery of large devices, 0.027 inch microcatheter and greater, for aneurysm treatment (n=108, 86%), intracranial angioplasty/stenting (n=15, 12%), and venous sinus stenting (n=2, 1.6%). All cases used a direct select catheter technique for initial guide placement (no exchange). Posterior circulation treatments occurred in 14.4% (n=18) of cases. Technical success was achieved in 100% of cases. No vessel dissections occurred in any cases. CONCLUSION: The TracStar LDP is an 0.088 inch 8Fr guide catheter that can establish direct intracranial access with an acceptable safety profile. This can be achieved in a wide range of neurointerventional cases with a high rate of technical success.

Triple Stentriever "Bouquet" Deployment with Zoom 88 Large-Bore Aspiration and Walrus Balloon-Guide Catheter for the Definitive Thrombectomy of a Carotid Free-Floating Thrombus.

Formation of a carotid free-floating thrombus (CFFT) is a rare and life-threatening condition without an optimal management plan. A 78-year-old woman with a history of prior right internal carotid artery (ICA) mechanical thrombectomy and antiplatelet noncompliance presented with transient ischemic attacks secondary to a recurrent CFFT in the right ICA. Given her symptoms and recurrent CFFT, endovascular mechanical thrombectomy was performed. A balloon guide-catheter (BGC) and a Zoom 88 distal access catheter were brought into the right distal common carotid artery and proximal ICA bulb, respectively. Three 0.021-inch microcatheters, each loaded with a unique stentriever, were navigated beyond the thrombus into the upper cervical ICA and deployed in a bouquet fashion. The BGC was inflated to achieve flow arrest, and the Zoom 88 aspiration catheter was tracked over the three bouquet stentrievers to ingest the thrombus. Follow-up angiography demonstrated recanalization of the proximal cervical ICA without evidence of residual thrombus. Twenty-four-hour postoperative computed tomography imaging did not reveal any evidence of new infarction. The patient was discharged home with an intact neurological examination, compliant on aspirin and apixaban. We demonstrate a novel technique utilizing a large-bore catheter with a triple stentriever "bouquet" to thrombectomize a CFFT.

Immediate procedural safety of adjunctive proximal coil occlusion in middle meningeal artery embolization for chronic subdural hematomas: Experience in 137 cases.

BACKGROUND: Endovascular embolization of the middle meningeal artery (MMA) has emerged as an adjunctive and stand-alone modality for the management of chronic subdural hematomas (cSDH). We report our experience utilizing proximal MMA coil embolization to augment cSDH devascularization in MMA embolization. METHODS: MMA embolization cases with adjunctive proximal MMA coiling were retrospectively identified from a prospectively maintained IRB-approved database of the senior authors. RESULTS: Of the 137 cases, all patients (n = 89, 100%) were symptomatic and underwent an MMA embolization procedure for cSDH. 50 of the patients underwent bilateral embolizations, with 53% (n = 72) for left-sided and 47% (n = 65) for right-sided cSDH. The anterior MMA branch was embolized in 19 (14%), posterior in 16 (12%), and both in 102 (74.5%) cases. Penetration of the liquid embolic to the contralateral MMA or into the falx was present in 38 (28%) and 31 (23%) cases, respectively, and 46 (34%) cases had ophthalmic or petrous collateral (n = 41, 30%) branches. MMA branches coiled include the primary trunk (25.5%, n = 35), primary and anterior or posterior MMA trunks (20%, n = 28), or primary with the anterior and posterior trunks (54%, n = 74). A mild ipsilateral facial nerve palsy was reported, which remained stable at discharge and follow-up. Absence of anterograde flow in the MMA occurred in 137 (100%) cases, and no cases required periprocedural rescue surgery for cSDH evacuation. The average follow-up length was 170 ± 17.9 days, cSDH was reduced by 4.24 ± 0.5(mm) and the midline shift by 1.46 ± 0.27(mm). Complete resolution was achieved in 63 (46.0%) cases. CONCLUSION: Proximal MMA coil embolization is a safe technique for providing additional embolization/occlusion of the MMA in cSDH embolization procedures. Further studies are needed to evaluate the potential added efficacy of this technique.

Augmentation of flow diverter vessel wall apposition using the Comaneci device: case experience from a novel, off-label technique.

BACKGROUND: Flow diversion (FD) embolization of intracranial cerebral aneurysms is an increasingly common modality where treatment success depends on adequate vessel wall apposition of the device. This study aimed to investigate off-label use of the Comaneci device for augmenting vessel wall apposition in post-deployed flow diversion stents (FDS). METHODS: Over a 20- month period, all FD cases for the treatment of internal carotid artery (ICA) aneurysms were reviewed. Cases in which the Comaneci device was used to augment vessel wall apposition were analyzed. Data including patient demographics, case characteristics, and procedural outcomes were collected and analyzed as counts. RESULTS: From a total of 74 ICA FD cases, the Comaneci device was used to improve vessel wall apposition in 22 cases (29.7%) . Of these cases, 91% were female with a mean patient age of 64.9±11.3 years, and an average aneurysm size of 4.5±2.5 mm. Comaneci device deployment and retrieval was successful in all (100%) cases, with an average fluoroscopy time of 27.3±7.8 min, an average contrast usage of 25.8±13.2 mL, and an average radiation exposure of 915.1±320.8 mGy. Only two cases (9%) required subsequent balloon angioplasty after Comaneci deployment to improve vessel wall apposition throughout the FDS. CONCLUSION: Our experience with this technique demonstrates the feasibility of using the Comaneci device for augmentation of FDS vessel wall apposition with 100% success in the deployment and retrieval of the Comaneci device.

Research progress in steroidal saponins from the genus Polygonatum: Chemical components, biosynthetic pathways and pharmacological effects.

The genus Polygonatum Mill. belongs to the Liliaceae family, which is widely distributed all over the world. Modern studies have found that Polygonatum plants are very rich in chemical compounds such as saponins, polysaccharides and flavonoids. Steroidal saponins are the most commonly studied saponins in the genus Polygonatum and a total of 156 compounds have been isolated from 10 species of the genus. These molecules possess antitumor, immunoregulatory, anti-inflammatory, antibacterial, antiviral, hypoglycemic, lipid-lowering and anti-osteoporotic activities. In this review, we summarize recent advances in studies of the chemical constituents of steroidal saponins from Polygonatum, including their structural characteristics, possible biosynthetic pathways and pharmacological effects. Then, the relationship between the structure and some physiological activities is considered. This review aims to provide reference for further exploitation and utilization of the genus Polygonatum.

Evaluation of the role of postoperative radiotherapy in locally invasive thymoma: A propensity-matched study based on the SEER database.

OBJECTIVES: No consensus was reached on the efficacy of postoperative radiotherapy (PORT) in locally invasive thymomas because of the rarity of the thymic epithelial and the variations of study results. Therefore, we aimed to explore the efficacy of PORT in locally invasive thymomas using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Patients diagnosed with thymomas from 2004 to 2016 were identified using the SEER database. Prognostic factors of cancer-specific survival (CSS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses.Propensity score matching (PSM) was performed to balance the baseline characteristics. RESULTS: A total of 700 eligible patients were identified. After PSM, 262 paired patients were selected from the two groups, those who received or did not receive PORT. Receiving PORT improved CSS and OS before and after PSM. In the matched population, the multivariate analyses showed that tumour invasion into adjacent organs/structures and non-utilisation of PORT were independent poor prognostic factors for CSS, whereas age ≥62 years,tumour invasion into adjacent organs/structures, and non-utilisation of PORT were independently associated with poorer OS. The subgroup analysis revealed that PORT improved CSS and OS in Masaoka-Koga stage III thymoma, but showed no OS benefit in Masaoka-Koga stage IIB thymoma. CONCLUSION: Based on the SEER database, we found that PORT provides a significant survival benefit in Masaoka-Koga stage III thymoma with complete or incomplete resection. The role of PORT in thymoma requires further evaluation.

COManeci MechANical Dilation for vasospasm (COMMAND): multicenter experience.

BACKGROUND: We report the largest multicenter experience to date of utilizing the Comaneci device for endovascular treatment of refractory intracranial vasospasm. METHODS: Consecutive patients undergoing Comaneci mechanical dilatation for vasospasm were extracted from prospectively maintained registries in 11 North American centers (2020-2022). Intra-arterial vasodilators (IAV) were allowed, with the Comaneci device utilized after absence of vessel dilation post-infusion. Pre- and post-vasospasm treatment scores were recorded for each segment, with primary radiological outcome of score improvement post-treatment. Primary clinical outcome was safety/device-related complications, with secondary endpoints of functional outcomes at last follow-up. RESULTS: A total of 129 vessels in 40 patients (median age 52 years; 67.5% females) received mechanical dilation, 109 of which (84.5%) exhibited pre-treatment severe-to-critical vasospasm (ie, score 3/4). Aneurysmal subarachnoid hemorrhage was the most common etiology of vasospasm (85%), with 65% of procedures utilizing Comaneci-17 (92.5% of patients received IAV). The most treated segments were anterior cerebral artery (34.9%) and middle cerebral artery (31%). Significant vasospasm drop (pre-treatment score (3-4) to post-treatment (0-2)) was achieved in 89.9% of vessels (96.1% of vessels experienced ≥1-point drop in score post-treatment). There were no major procedural/post-procedural device-related complications. Primary failure (ie, vessel unresponsive) was encountered in one vessel (1 patient) (1/129; 0.8%) while secondary failure (ie, recurrence in previously treated segment requiring retreatment in another procedure) occurred in 16 vessels (7 patients) (16/129; 12.4%), with median time-to-retreatment of 2 days. Favorable clinical outcome (modified Rankin Scale 0-2) was noted in 51.5% of patients (median follow-up 6 months). CONCLUSIONS: The Comaneci device provides a complementary strategy for treatment of refractory vasospasm with reasonable efficacy/favorable safety. Future prospective trials are warranted.

[Associations Among Changes in Meridian Energy, Quality of Life During Surgery, and Prognoses in Newly Diagnosed Lung Cancer Patients: A Longitudinal Study].

BACKGROUND: Approximately 30% of patients experience postoperative complications after surgery for early-stage lung cancer. However, the relationships among meridian energy during lung cancer surgery, changes in quality of life, and prognosis have not been investigated. PURPOSE: This study was designed to explore the associations among meridian energy, changes in quality of life, and prognosis in patients with newly diagnosed lung cancer undergoing surgery. METHODS: A longitudinal, repeated-measures design was used. Basic data forms, meridian energy measurements, and a concise 12-item health status questionnaire were administered to the participants at the time of diagnosis, 2 weeks post-surgery, and 12 weeks post-surgery. During this period, changes were analyzed, and their association with postoperative risks was explored. RESULTS: Forty-eight cases were investigated. Both meridian energy and quality of life were found to be significantly decreased 2 weeks after surgery. The high/low ratio of meridian energy, the physical component score of the Short Form 12-Item Health Survey Questionnaire, gender, cancer stage, and body mass index were identified as significantly associated with prognosis. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Conclusion/Implications for Practice: The declining trends in meridian energy and quality of life during the 2 weeks after surgery in patients with lung cancer are associated with poor postoperative prognoses. Nurses may use the findings of this study to identify patients at high risk of postoperative complications and develop appropriate strategies to provide comprehensive care.

An in vivo and in vitro assessment of the anti-breast cancer activity of crude extract and fractions from Prunella vulgaris L.

Prunella vulgaris L.(P. vulgaris) is a perennial herb belonging to the Labiate family and widely distributed in China, Japan, Korea and Europe. Medical monographs and previous studies have shown that P. vulgaris has significant anti-breast cancer activity, and its use in breast treatment has a long history. However, systematically reports about the material basis and mechanism of P. vulgaris on anti-breast cancer activity are limited. In the present study, we first screened the best active fraction from the crude extract (PVE) and ethanol eluted fractions of P. vulgaris by using MDA-MB-231, MCF-7, 4T1 cell models in vitro and a 4T1-BALB/c transplanted tumour mouse breast cancer model in vivo. Furthermore, the anti-breast cancer mechanism of the best active fraction was investigated. The results demonstrated that PVE and ethanol fractions exhibited anti-breast cancer activity, especially with the 50% ethanol eluted fraction (PV50), which effectively regulated the 4T1 cell cycle, inhibited tumour cell proliferation, and promoted cancer cell apoptosis. In case of in vivo assays, PV50 inhibited tumour growth and lung metastasis, as well as inducing cell apoptosis by promoting damage of nuclear DNA and increasing expression of cleaved caspase-3. In addition, the chemical compositions of PV50 were analyzed by HPLC and UPLC-MS/MS, which were identified as flavonoids, moderately polar triterpenes, and a small amount of phenolic acid. The PV50 could be applied as natural sources against breast cancer in the pharmaceutical industry. These findings provide a basis for understanding the mechanism of the anti-breast cancer activity of P. vulgaris.

Comparison of diagnostic accuracy of three-dimensional transvaginal ultrasound and magnetic resonance imaging in the diagnosis of scar pregnancy.

Objectives: To compare the accuracy of three-dimensional transvaginal ultrasound and magnetic resonance imaging in the diagnosis of scar pregnancy. Methods: The records of 54 patients with scar pregnancy, who underwent three-dimensional transvaginal ultrasound and magnetic resonance imaging (MRI), from June 2015 to November 2021 were reviewed. Surgery / histopathology of operative findings were analyzed as gold standard to compare the diagnosis of the two examination methods. Results: The detection rate of scar pregnancy by three-dimensional transvaginal ultrasound was 94.44%, which was not significantly different from MRI (96.30%, P>0.05). The accuracy, specificity and sensitivity of transvaginal three-dimensional ultrasonography in the diagnosis of scar pregnancy were 94.44%, 66.67% and 96.08%, respectively, and were not significantly different from MRI, 96.30%, 50.00% and 98.08% (P>0.05). The detection rates of yolk sac, embryo and heart tube pulsation by three-dimensional transvaginal ultrasound were higher than those detected by MRI (P<0.05). The detection rates of intrathecal hemorrhage, scar infiltration and uterine hematocele by MRI were significantly higher compared to three-dimensional transvaginal ultrasound (P<0.05). There was no significant difference between the two methods (P>0.05). Conclusion: Both three-dimensional transvaginal ultrasound and MRI have good diagnostic efficacy in the diagnosis of scar pregnancy. Detection rates of scar pregnancy diagnostic criteria differ between the two methods, and if necessary, the two methods can be used together, to further improve the diagnostic accuracy of scar pregnancy.

Sanguinarine protects against indomethacin-induced small intestine injury in rats by regulating the Nrf2/NF-κB pathways.

In recent years, small intestine as a key target in the treatment of Inflammatory bowel disease caused by NSAIDs has become a hot topic. Sanguinarine (SA) is one of the main alkaloids in the Macleaya cordata extracts with strong pharmacological activity of anti-tumor, anti-inflammation and anti-oxidant. SA is reported to inhibit acetic acid-induced colitis, but it is unknown whether SA can relieve NSAIDs-induced small intestinal inflammation. Herein, we report that SA effectively reversed the inflammatory lesions induced by indomethacin (Indo) in rat small intestine and IEC-6 cells in culture. Our results showed that SA significantly relieved the symptoms and reversed the inflammatory lesions of Indo as shown in alleviation of inflammation and improvement of colon macroscopic damage index (CMDI) and tissue damage index (TDI) scores. SA decreased the levels of TNF-α, IL-6, IL-1ß, MDA and LDH in small intestinal tissues and IEC-6 cells, but increased SOD activity and ZO-1 expression. Mechanistically, SA dose-dependently promoted the expression of Nrf2 and HO-1 by decreasing Keap-1 level, but inhibited p65 phosphorylation and nuclear translocation in Indo-treated rat small intestine and IEC-6 cells. Furthermore, in SA treated cells, the colocalization between p-p65 and CBP in the nucleus was decreased, while the colocalization between Nrf2 and CBP was increased, leading to the movement of gene expression in the nucleus to the direction of anti-inflammation and anti-oxidation. Nrf2 silencing blocked the effects of SA. Together our results suggest that SA can significantly prevent intestinal inflammatory lesions induced by Indo in rats and IEC-6 cells through regulation of the Nrf2 pathway and NF-κBp65 pathway.

[Differences of flavor compounds in Lonicerae Japonicae Flos and Lonicerae Flos based on headspace gas chromatography-ion mobility spectroscopy].

Lonicerae Japonicae Flos and Lonicerae Flos, as traditional Chinese medicinal and edible food, are widely used in medicine, food, health products, and other industries. However, there is no comprehensive study on the differences of flavor compounds in Lonicerae Japonicae Flos and Lonicerae Flos. This study applied headspace gas chromatography-ion mobility spectrometry(HS-GC-IMS) to analyze the differences of flavor compounds in Lonicerae Japonicae Flos and Lonicerae Flos. The differential biomarkers were confirmed by multivariate statistical analysis. The results showed that there were significant differences in the forty-seven flavor compounds in Lonicerae Japonicae Flos and Lonicerae Flos. The differential markers were ethyl acetate, propyl alcohol, 1-octanol, 1-hexanol, hexanal, and(Z)-2-hexen-1-ol. Pathway enrichment analysis showed that the above markers were involved in the biosynthesis of major secondary metabolism, sulfate metabolism pathways, and formation of other flavor compounds. This study provides important references for the evaluation of flavor compounds of Lonicerae Japonicae Flos and Lonicerae Flos and the development of medicinal and edible products.

Transcriptome and Metabolome Analysis of the Synthesis Pathways of Allelochemicals in Eupatorium adenophorum.

Eupatorium adenophorum (Crofton weed) is an invasive weed in more than 30 countries. It inhibits the growth of surrounding plants by releasing allelochemicals during its invasion. However, the synthetic pathways and molecular mechanisms of its allelochemicals have been rarely reported. In this study, the related genes and pathways of allelochemicals in E. adenophorum were analyzed. Transcriptome analysis showed that differentially expressed genes (DEGs) were mainly enriched in the phenylpropanoid biosynthetic pathway and flavonoid biosynthetic pathway. Thirty-three DEGs involved in the synthesis of allelochemicals were identified, and 30 DEGs showed significant differences in blades and stems. Six allelochemicals were identified from blades and stems by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Correlation analysis of genes and metabolites showed a strong correlation between the five genes and allelochemicals. In addition, this study supplemented the biosynthetic pathway of Eupatorium adenophorum B (HHO). It was found that acyclic sesquiterpene synthase (NES), δ-cadinene synthase (TPS), and cytochrome P450 (P450) were involved in the synthesis of HHO. These findings provide a dynamic spectrum consisting of allelochemical metabolism and a coexpression network of allelochemical synthesis genes in E. adenophorum.

Adjuvant radiotherapy shows benefit in selected stage I uterine sarcoma: A risk scoring system based on a population analysis.

BACKGROUND: The potential therapeutic benefit of adjuvant radiotherapy for patients with stage I uterine sarcoma has not been clear. In this study, we aimed to develop a risk scoring model to select the subgroup of patients with stage I uterine sarcoma who might benefit from adjuvant radiotherapy. METHODS: Patients with stage I uterine sarcoma from the Surveillance, Epidemiology, and End Results program from 2010 to 2014 were retrospectively included in this analysis. Cox proportional hazards models were performed to identify risk factors. RESULTS: A total of 947 stage I uterine sarcoma patients were included. The 5-year disease-specific survival (DSS) of the overall cohort was 75.81%. Multivariate analysis identified stage (p = 0.013), tumor grade (p <0.001) and histology (p = 0.043) as independent prognostic factors for DSS, and these factors were used to generate the risk scoring model. The low-risk group presented a better DSS than the high-risk group (95.51% vs. 49.88%, p < 0.001). The addition of radiotherapy to surgery significantly increased the DSS in the high-risk group compared with surgery alone (78.06% vs. 46.88%, p = 0.022), but no significant survival benefit was observed in the low-risk group (98.36% vs. 100%, p = 0.766). CONCLUSIONS: Our risk scoring model based on stage, tumor grade, and histology predicted the outcome of patients with stage I uterine sarcoma cancer. This system may help to select stage I uterine sarcoma cancer patients who might benefit from adjuvant radiotherapy.

Discovery and development of a novel N-(3-bromophenyl)-{[(phenylcarbamoyl)amino]methyl}-N-hydroxythiophene-2-carboximidamide indoleamine 2,3-dioxygenase inhibitor using knowledge-based drug design.

Indoleamine 2,3-dioxygenase-1 (IDO1) is a potential target for the next generation of cancer immunotherapies. We describe the development of two series of IDO1 inhibitors incorporating a N-hydroxy-thiophene-carboximidamide core generated by knowledge-based drug design. Structural modifications to improve the cellular activity and pharmacokinetic (PK) properties of the compounds synthesized, including extension of the side chain of the N-hydroxythiophene-2-carboximidamide core, resulted in compound 27a, a potent IDO1 inhibitor which demonstrated significant (51%) in vivo target inhibition on IDO1 in a human SK-OV-3 ovarian xenograft tumor mouse model. This strategy is expected to be applicable to the discovery of additional IDO1 inhibitors for the treatment of other diseases susceptible to modulation of IDO1.

Metabolomics and pharmacodynamic analysis reveal the therapeutic role of Prunella vulgaris oil on intrauterine adhesion rats.

Metabolomics is applied to explore the curative effect of complex systems, such as Chinese medicine. Intrauterine adhesion (IUA) harms the reproductive system and affects fertility, and hence is a significant public health concern. Prunella vulgaris oil (PVO) protects the reproductive system and exerts anti-inflammatory effects, but its effect on IUA and the underlying mechanism is unclear. In this study, we established a serum metabolomics method based on GC-TOF-MS to evaluate the mechanism of PVO in the IUA rat model established by mechanical injury and infection. Animal experiments showed that PVO improves the inflammatory response in the uterus of IUA model rats and reduces the content of inflammatory factors to improve the microenvironment of the reproductive system. It also regulates the expression of TGF-ß1 and Smad-related mRNA and protein to inhibit fibrosis. Metabolomics indicated a significant abnormality in serum metabolism in IUA rats, and a total of 51 differential markers were screened and identified. After PVO treatment, these metabolic abnormalities improved significantly. The metabolic pathway analysis revealed that PVO affects glyoxylate and dicarboxylate metabolism, and ß-alanine metabolism pathways. This study showed that PVO significantly improves inflammation and fibrosis in IUA rats combined with the pharmacological results. The primary mechanism is related to regulating the metabolism of amino acids and their derivatives to balance the associated disorders and control energy metabolism.

In silico/computational analysis of mevalonate pyrophosphate decarboxylase gene families in Campanulids.

Mevalonate pyrophosphate decarboxylase (MPD) is a key enzyme in terpenoid biosynthesis. MPD plays an important role in the upstream regulation of secondary plant metabolism. However, studies on the MPD gene are relatively very few despite its importance in plant metabolism. Currently, no systematic analysis has been conducted on the MPD gene in plants under the order Apiales, which comprises important medicinal plants such as Panax ginseng and Panax notoginseng. This study sought to explore the structural characteristics of the MPD gene and the effect of adaptive evolution on the gene by comparing and analyzing MPD gene sequences of different campanulids species. For that, phylogenetic and adaptive evolution analyses were carried out using sequences for 11 Campanulids species. MPD sequence characteristics of each species were then analyzed, and the collinearity analysis of the genes was performed. As a result, a total of 21 MPD proteins were identified in 11 Campanulids species through BLAST analysis. Phylogenetic analysis, physical and chemical properties prediction, gene family analysis, and gene structure prediction showed that the MPD gene has undergone purifying selection and exhibited highly conserved structure. Analysis of physicochemical properties further showed that the MPD protein was a hydrophilic protein without a transmembrane region. Moreover, collinearity analysis in Apiales showed that MPD gene on chromosome 2 of D. carota and chromosome 1 of C. sativum were collinear. The findings showed that MPD gene is highly conserved. This may be a common characteristic of all essential enzymes in the biosynthesis pathways of medicinal plants. Notably, MPD gene is significantly affected by environmental factors which subsequently modulate its expression. The current study's findings provide a basis for follow-up studies on MPD gene and key enzymes in other medicinal plants.