Antihyperglycemic effects of triterpenoid saponins from the seeds of Aesculus chinensis Bge.

Six undescribed triterpenoid saponins, namely aescuchinosides A-F, along with seven known triterpenoid saponins, were isolated from the seeds of Aesculus chinensis. Barrigenol-like triterpenoids (BATs) constitute these saponins. Protoaescigenin serves as their aglycone, with various oxygen-containing groups, including acetyl, isobutyryl, tigloyl, and angeloyl groups situated at C-21, C-22, and C-28. Various techniques, including 1D and 2D-NMR spectroscopy, high-resolution mass spectrometry, and acid hydrolysis, were employed to determine the structures of these compounds. The antihyperglycemic effects of the isolated compounds were examined in insulin -resistant HepG2 cells induced by palmitic acid treatment. At a concentration of 6 µM, aesculinoside F exhibited a significant increase in glucose consumption. In addition, aesculinoside F demonstrated the potential to improve insulin resistant by upregulating the PI3K/AKT pathway. These results indicate that the seeds of A.chinensis hold promising potential for preventing insulin resistant related disease.

Effect of individualized nutritional intervention on head and neck cancer patients receiving radiotherapy.

OBJECTIVE: To explore the effect of individualized nutritional interventions on head and neck cancer (HNC) patients receiving radiotherapy and provide a basis for improving the quality of life for those patients. METHODS: A convenience sampling method was adopted to select HNC patients as the study objects. The Nutritional Risk Screening 2002 scale (NRS2002) was used to screen the nutritional risk in 108 HNC patients receiving radiotherapy, and the patients were randomly divided into control group and observation group. Routine dietary guidance was conducted in the control group, and individualized nutritional intervention was applied in the observation group. RESULTS: Six months after the intervention, the albumin levels (37.40 ± 4.03 g/L), hemoglobin levels (128.70 ± 15.22 g/L), and body mass index scores (BMI) (23.96 ± 3.23 kg/m2) of the observation group were all better than to those of control group (t = 2.370, 2.216, and 3.135, respectively, and P < 0.05 in all). Six months after the intervention, the anxiety and depression scores in observation group (27.6 ± 7.2 points, 27.3 ± 2.2 points) were lower than those in control group (38.6 ± 9.6 points, 37.9 ± 3.3 points). The quality-of-life score in the observation group was higher than that in control group. The nursing satisfaction in the observation group (96.43%) was higher than that in the control group (75.00%). CONCLUSION: The implementation of individualized nutritional intervention has promoted the improvement of laboratory indicators, weight, and BMI of head and neck cancer patients, reduced the risk of malnutrition of head and neck cancer patients, improved their quality of life, reduced the occurrence of adverse reactions during radiotherapy, and promoted long-term efficacy.

Intrathecal drug-infusion system for treating pain in advanced cancer: New research in patient management.

Currently, the treatment of cancer pain in China mainly follows the three-step pain relief principles formulated by the World Health Organization. As research on subarachnoid drug diffusion has intensified, intrathecal drug delivery has been gradually applied in the treatment of diseases, and improved analgesia can be achieved via the continuous infusion of small doses of morphine-derived drugs. This method can not only effectively relieve pain and enhance quality of life but also significantly reduce the incidence of nausea, vomiting, constipation, and other adverse reactions caused by the long-term intensive use of drugs in patients with cancer pain. This study summarizes the development of the intrathecal drug-infusion system for treating cancer pain in patients with advanced cancer and describes the drugs used, the advantages in pain treatment, and key nursing factors before and after device placement to provide a basis for alleviating pain in patients with cancer.

Thrombosis density ratio can predict the occurrence of pulmonary embolism and post-thrombotic syndrome in lower-extremity deep vein thrombosis patients.

OBJECTIVE: Deep vein thrombosis (DVT) formation of lower extremities can lead to serious complications including pulmonary embolism (PE) and chronic post-thrombotic syndrome (PTS). We aimed to explore the relationship between the ratio of thrombotic density and the occurrence of PE and PTS in patients with DVT of the lower extremities. METHODS: A retrospective analysis was conducted in patients who performed computed tomography venography, dividing into DVT with PE group (54 patients) and DVT-alone group (34 patients), The clinical data were recorded. Univariate and multivariate logistic regression analysis were used to analysis variables associated with PE. The ability of thrombosis density ratio and Wells score to diagnose PE was evaluated by using the receiver operating characteristic curve (ROC) area under the curve (AUC). According to the treatment and follow-up results, subgroup analysis was performed, and the Villata score was used to determine the presence or absence of PTS and its severity. RESULTS: Compare with the DVT-alone group, more patients had dyspnea and chest pain in the DVT with PE group. DVT with PE group had lower the percentage of neutrophils, white blood cell count and platelet count, while had higher blood cell count, D-dimer, wells score, thrombus and thrombus density ratio. Multivariate logistic analysis showed that percentage of neutrophils (OR(95% CIs)=1.15 (1.01,1.31), P = 0.040), platelets (OR(95% CIs)=0.96 (0.93,0.99), P = 0.011), and thrombus density ratio (OR(95% CIs)=5.99 (1.96,18.35), P = 0.002) are independent predictors of PE. The Wells score and thrombosis density ratio were consistent in the diagnostic efficacy of PE. In the subgroup analysis, there was a relevance between the ratio of thrombosis density and the Villalta score. CONCLUSION: Percentage of neutrophils, platelets, and thrombus density ratio are independent predictors of PE. The thrombosis density of DVT patients may be an index to predict the risk of PE and PTS in DVT patients.

Establishment and evaluation of the impact of a supervisory group for chemotherapy safety management in an oncology department.

BACKGROUND: The nursing model of establishing a chemotherapy safety management supervisory group has guaranteed the safety and effectiveness of intravenous chemotherapy while reducing the adverse effects of chemotherapy and improving patient satisfaction and quality of life. OBJECTIVE: To explore the impact of establishing a nursing supervision group on improving the safety management of patients receiving chemotherapy in the oncology department. METHODS: We selected a total of 60 patients who underwent chemotherapy at the oncology department between January and June 2021 and assigned them to the control group. They received conventional chemotherapy safety management nursing care. We selected another 60 patients undergoing chemotherapy in the oncology department between July and December 2021 and assigned them to the observation group. They received a nursing intervention model facilitated by the chemotherapy safety supervision team. We compared the intervention effects in the two groups. RESULTS: Patient satisfaction was significantly higher in the observation group than in the control group (P< 0.05); the incidence of post-chemotherapy nausea and vomiting was significantly lower in the observation group than in the control group (P< 0.05); and the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients in the observation group were reduced (P< 0.05) and significantly lower than in the control group (P< 0.05). We used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC-QLQ-C30) and found a statistically significant difference in the quality of life of patients before the nursing intervention and on the day of discharge (P< 0.05). CONCLUSION: The establishment of a chemotherapy safety management supervisory group was effective in reducing the incidence of post-chemotherapy nausea and vomiting as well as the patient's psychological burden; it could also improve the quality of life of patients and their satisfaction with nursing care.

Garbractin A, a Polycyclic Polyprenylated Acylphloroglucinol with a 4,11-dioxatricyclo[4.4.2.01,5]Dodecane Skeleton from Garcinia bracteata Fruits.

Garbractin A (1), a structurally complicated polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented 4,11-dioxatricyclo[4.4.2.01,5] dodecane skeleton, was isolated from the fruits of Garcinia bracteata, along with five new biosynthetic analogues named garcibracteatones A-E (2-6). Their structures containing absolute configurations were revealed using spectroscopic data, the residual dipolar coupling-enhanced NMR approach, and quantum chemical calculations. The antihyperglycemic effect of these PPAPs (1-6) was evaluated using insulin-resistant HepG2 cells (IR-HepG2 cells) induced through palmitic acid (PA). Compounds 1, 3, and 4 were found to significantly promote glucose consumption in the IR-HepG2 cells and, therefore, may hold potential as candidates for treating hyperglycemia.

Malnutrition in patients with head and neck cancer undergoing radiotherapy: A cross-sectional study.

OBJECTIVE: In this study, we investigated the prevalence of malnutrition and analyzed the related factors among patients with head and neck cancer (HNC) undergoing radiotherapy. METHODS: We included 108 patients with head and neck cancer undergoing radiotherapy from the oncology and thoracic surgery departments of a comprehensive medical center in Qingdao between January 2019 and June 2020. We used the Nutritional Risk Screening-2002 tool (NRS-2002) to evaluate their nutritional status during radiotherapy. We analyzed the basic sociodemographic information and laboratory indicators of the respondents to examine the impact of these factors on nutritional status. RESULTS: In the 108 patients that we studied, those aged ≥65 years had a significantly higher nutritional risk when compared to patients <65 years of age (P < 0.05). Univariate analysis revealed that a late tumor stage (P = 0.039), the neck being the site of radiotherapy (P = 0.009), the presence of diabetes (P < 0.001), and the presence of anxiety and depression (P = 0.002) were associated with nutritional risks for patients with head and neck cancer undergoing radiotherapy. Multivariate logistic regression analysis identified a late tumor stage, the neck being the radiotherapy site, and combined anxiety and depression as nutritional risk factors in such patients. CONCLUSION: We found a high incidence of malnutrition in patients undergoing radiotherapy for HNC; this highlights the importance of early identification of patients at risk and evaluation of related risk factors to enhance the efficacy of nutritional interventions.

A Self-Powered Piezoelectric Nanofibrous Membrane as Wearable Tactile Sensor for Human Body Motion Monitoring and Recognition.

Wearable sensors have drawn vast interest for their convenience to be worn on body to monitor and track body movements or exercise activities in real time. However, wearable electronics rely on powering systems to function. Herein, a self-powered, porous, flexible, hydrophobic and breathable nanofibrous membrane based on electrospun polyvinylidene fluoride (PVDF) nanofiber has been developed as a tactile sensor with low-cost and simple fabrication for human body motion detection and recognition. Specifically, effects of multi-walled carbon nanotubes (CNT) and barium titanate (BTO) as additives to the fiber morphology as well as mechanical and dielectric properties of the piezoelectric nanofiber membrane were investigated. The fabricated BTO@PVDF piezoelectric nanogenerator (PENG) exhibits the high ß-phase content and best overall electrical performances, thus selected for the flexible sensing device assembly. Meanwhile, the nanofibrous membrane demonstrated robust tactile sensing performance that the device exhibits durability over 12,000 loading test cycles, holds a fast response time of 82.7 ms, responds to a wide pressure range of 0-5 bar and shows a high relative sensitivity, especially in the small force range of 11.6 V/bar upon pressure applied perpendicular to the surface. Furthermore, when attached on human body, its unique fibrous and flexible structure offers the tactile sensor to present as a health care monitor in a self-powered manner by translating motions of different movements to electrical signals with various patterns or sequences. Supplementary Information: The online version contains supplementary material available at 10.1007/s42765-023-00282-8.

Isolation and antihyperglycemic effects of garcibractinols A-H, intricate polycyclic polyprenylated acylphloroglucinols from the fruits of Garcinia bracteata.

Eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from the fruits of Garcinia bracteata and named garcibractinols A-H. Garcibractinols A-F (compounds 1-6) were bicyclic polyprenylated acylphloroglucinols (BPAPs) sharing a rare bicyclo[4.3.1]decane core. On the other hand, garcibractinols G and H (compounds 7 and 8) shared an unprecedented BPAP skeleton bearing a 9-oxabicyclo[6.2.1]undecane core. The structures andabsolute configurations of compounds 1-8 were determined by spectroscopic analysis,single-crystal X-ray diffraction analysis, and quantum chemical calculation. The breakage of the C-3/C-4 linkage through the retro-Claisen reaction was a key step in the biosynthesis of compounds 7 and 8. The antihyperglycemic effects of the eight compounds were evaluated in insulin-resistant HepG2 cells. At a concentration of 10 µM, compounds 2 and 5-8 significantly increased the glucose consumption in the HepG2 cells. Furthermore, compound 7 was more effective than metformin (which was used as a positive control) in promoting glucose consumption in the cells. The findings of this study suggest that compounds 2 and 5-8 have anti-diabetic effects.

Solar X-ray and EUV imager on board the FY-3E satellite.

The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42', an angular resolution of 2.5″ per pixel in the EUV band and an angular resolution of 4.1″ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.

Complete genome sequence of piezotolerant Stutzerimonas kunmingensis 7850S isolated from the sediment of the Mariana Trench.

Stutzerimonas kunmingensis 7850S is a piezotolerant bacterium isolated from the sediment of the Mariana trench. Here, we described the complete genome of strain 7850S, which contains a single circular chromosome of 4,775,870 base pairs with 62.66% G + C content, and harbors 4494 protein-coding genes, 65 transfer RNA genes, and 12 ribosomal RNA genes. The experimental results showed that strain 7850S could grow under hydrostatic pressure of 0.1-70 MPa. Genomic analyses led to identifications of numbers of high hydrostatic pressure-associated genes, such as the ones associated with unsaturated fatty acids, betaine, and ectoine. A complete set of denitrification genes and some heavy metal detoxification genes were also found in this strain. The presence of these genes suggests metabolic characteristics for adaption to hadal environments and provides insights to further understand adaption strategies and ecological roles of Stutzerimonas in hadal environments.

Chemical constituents from the seeds of Nigella glandulifera and their hypoglycemic activities.

The seeds of Nigella glandulifera Freyn et Sint. are traditional Uygur medicine used for the treatment of diabetes. However, the active anti-diabetic constituents in the seeds of N. glandulifera remain unclear. In the present study, a new delabellane-type diterpene, 8-denicotinoylnigellamine A1 (1), and a new acyclic sesquiterpene, 2,6,10-trimethyl-6,7,12-trihydroxy-dodec-2-ene (3), together with eight known compounds including alkaloids (2 and 7), triterpenoid saponins (4-6), and phenolic compounds (8-10), were isolated from the seeds of N. glandulifera. Their structures were determined by extensive spectroscopic analyses and quantum chemical calculations. We evaluated the potential protective effects of the isolated compounds on an insulin resistant HepG2 (IR-HepG2) cell model. The results showed that compounds 2, 4-8, and 10 could promote the consumption of glucose in IR-HepG2 cells. Those compounds might be responsible for the anti-diabetic effects of the seeds of N. glandulifera.

Curcumae rhizoma and its major constituents against hepatobiliary disease: Pharmacotherapeutic properties and potential clinical applications.

BACKGROUND: Hepatobiliary disease currently serves as an urgent health issue in public due to health-modulating factors such as extension of life expectancy, increasingly sedentary lifestyles and over-nutrition. A definite treatment remains lacking owing to different stages of the disease itself and its intricate pathogenesis. Traditional Chinese medicine (TCM) has been gradually popularized in clinic with the satisfactory efficacy and good safety. Curcumae Rhizoma (called E Zhu, EZ in Chinese) is a representative herb, which has been used to treat hepatobiliary disease for thousands of years. PURPOSE: To systematically summarize the recent research advances on the pharmacological activities of EZ and its constituents, explain the underlying mechanisms of preventing and treating hepatobiliary diseases, and assess the shortcomings of existing work. Besides, ethnopharmacology, phytochemicals, and toxicology of EZ have been researched. METHODS: The information about EZ was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, CSTJ, and WANFANG using keywords given below and terms like pharmacological and phytochemical details of this plant. RESULTS: The chemical constituents isolated and identified from EZ, such as terpenoids including ß-elemene, furanodiene, germacrone, etc. and curcuminoids including curcumin, demethoxycurcumin, bisdemethoxycurcumin, etc. prove to have hepatoprotective effect, anti-liver fibrotic effect, anti-fatty liver effect, anti-liver neoplastic effect, and cholagogic effect through TGF-ß1/Smad, JNK1/2-ROS, NF-κB and other anti-inflammatory and antioxidant signaling pathways. Also, EZ is often combined with other Chinese herbs in the treatment of hepatobiliary diseases with good clinical efficacy and no obvious adverse reactions. CONCLUSION: It provides a preclinical basis for the efficacy of EZ as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases. Even so, the further studies still needed to alleviate hepatotoxicity and expand clinical application.

Phenolic Compounds From the Stems and Leaves of Berchemia lineata (L.) DC.

Eight new phenolic compounds, named bercheminols A-H (1-8), and eleven known analogues were isolated from the stems and leaves of Berchemia lineata (L.) DC. Their structures including the absolute configurations were elucidated by extensive spectroscopic analysis, chemical method, and quantum chemical calculations. Compound 1 possesses an unprecedented 3,4-dihydro-11H-benzo[b]pyrano[4,3-e] oxepin-11-one skeleton. The other new compounds belong to three structural types of natural products, including naphthopyrones (2-5), flavonoids (6-7), and bibenzyl (8). The α-glucosidase inhibitory activities of the isolated compounds were assayed. As a result, vittarin-B (9), rubrofusarin-6-O-ß-D-glucopyranoside (11), quercetin (14), kaempferol (15), and dihydrokaempferol (17) showed moderate inhibitory activities against α-glucosidase with IC50 values of 22.5, 28.0, 36.5, 32.7, and 31.9 µM, respectively.

[Identification and expression analysis of NRT1 family genes in Rehmannia glutinosa].

NRT1 family proteins play an important roles for absorbing and transporting of nitrate in different plants. In order to identify the NRT1 family genes of Rehmannia glutinosa, this study used 11 NRT1 homologous proteins of Arabidopsis as probe sequences and aligned with the transcriptome data of R. glutinosa by using NCBI BLASTN software. Resulting there were 18 NRT1 proteins were identified in R. glutinosa. On basis of this, a series of the molecular characteristics of R. glutinosa NRT1 proteins including the conserved domains, the transmembrane structure, the subcellular location and phylogenetic features were in detail analyzed. At same time, it were systematically analyzed that the temporal and spatial expression patterns and characteristics of R. glutinosa NRT1 family genes in response to different stress factors. The results indicated that 18 R. glutinosa NRT1 family genes with the length of coding region from 1 260 bp to 1 806 bp, encoded proteins ranging from 419 to 601 amino acids, and all of they owned the domains of typical peptide transporter with 7 to 12 transmembrane domains. These R. glutinosa NRT1 family proteins mostly were found to locate on cellular plasma membrane, and belonged to the hydrophobic proteins. Furthermore, the evolutionary analysis found that the 18 R. glutinosa NRT1 protein family could be divided into two subfamilies, of which 14 NRT1 family genes might occur the positive selection, and 4 genes occur the passivation selection during the evolution process of R. glutinosa. In addition the expression analysis showed that 18 R. glutinosa NRT1 family genes have the distinct expression patterns in different tissues of R. glutinosa, and their expression levels were also obvious difference in response to various stress. These findings infield that 18 R. glutinosa NRT1 family proteins might have obviously different functional roles in nitrate transport of R. glutinosa. In conclusion, this study lays a solid theoretical foundation for clarifying the absorption and transport molecular mechanism of N element during R. glutinosa growth and development, and at same time for deeply studying the molecular function of R. glutinosa NRT1 proteins in absorption and transport of nitrate.

N-trans-Feruloyloctopamine Wakes Up BBC3, DDIT3, CDKN1A, and NOXA Signals to Accelerate HCC Cell Apoptosis.

N-trans-Feruloyloctopamine (FO), a natural compound, was reported in our previous study to inhibit a tumor cell malignant phenotype by AKT- and EMT-related signals and might be used as a promising drug for HCC treatment. However, the specific targets and detailed mechanisms still need to be clarified. Screening with RNA-Seq in Huh7 cells treated with FO revealed that 317 genes were modulated, of which 188 genes were upregulated and 129 genes were downregulated. Real-time cell analyzer and flow cytometry data reveal that tumor cell proliferation and apoptosis were impacted by FO. DAVID bioinformatic data showed that most of the biological process GO terms are related to proliferation and apoptosis. KEGG enrichment analysis showed that FO mainly regulates PI3K-AKT- and apoptosis-related signals, in which BBC3, DDIT3, NOXA, and CDKN1A on the surface serve as the novel targets of FO inducing HCC cell apoptosis. The result implied that FO might exacerbate HCC cell apoptosis by regulating BBC3, DDIT3, CDKN1A, and NOXA signals. The obstacle effect of FO can provide new targets and new credibility for the treatment of liver cancer.

Myxofibrosarcoma of the scalp with difficult preoperative diagnosis: A case report and review of the literature.

BACKGROUND: A myxofibrosarcoma (MFS) is a malignant fibroblastic tumor that tends to occur in the lower and upper extremities. The reported incidence of head and neck MFSs is extremely rare. We report a 46-year-old male with "a neoplasm in the scalp" who was hospitalized and diagnosed with an MFS (highly malignant with massive necrotic lesions) based on histologic and immunohistochemistry evaluations. The magnetic resonance imaging manifestations did not demonstrate the "tail sign" mentioned in several studies, which resulted in a great challenge to establish an imaging diagnosis. The treatment plan is closely associated with the anatomic location and histologic grade, and more importantly, aggressive surgery and adjuvant radiotherapy may be helpful. Hence, we report the case and share some valuable information about the disease. CASE SUMMARY: A 46-year-old male with "a neoplasm in the scalp for 6 mo" was hospitalized. Initially, the tumor was about the size of a soybean, without algesia or ulceration. The patient ignored the growth, did not seek treatment, and thus, did not receive treatment. Recently, the tumor increased to the size of an egg; there was no bleeding or algesia. His family history was unremarkable. No abnormalities were found upon laboratory testing, including routine hematologic, biochemistry, and tumor markers. Computed tomography showed an ovoid mass (6.25 cm × 3.29 cm × 3.09 cm in size) in the left frontal scalp with low density intermingled with equidense strips in adjacent areas of the scalp. Magnetic resonance imaging revealed a lesion with an irregular surface and an approximate size of 3.55 cm × 6.34 cm in the left frontal region, with clear boundaries and visible separation. Adjacent areas of the skull were damaged and the dura mater was involved. Contrast enhancement showed an uneven enhancement pattern. Surgery was performed and postoperative adjuvant radiotherapy was administered to avoid recurrence or metastasis. The post-operative pathologic diagnosis confirmed an MFS. A repeat computed tomography scan showed no local recurrence or distant metastasis 19 mo post-operatively. CONCLUSION: The case reported herein of MFS was demonstrated in an extremely rare location on the scalp and had atypical magnetic resonance imaging findings, which serves as a reminder to radiologists of the possibility of this diagnosis to assist in clinical treatment. Given the special anatomic location and the high malignant potential of this rare tumor, combined surgical and adjuvant radiotherapy should be considered to avoid local recurrence and distant metastasis. The significance of regular follow-up is strongly recommended to improve the long-term survival rate.

Cardiolipin Synthase 1 Ameliorates NASH Through Activating Transcription Factor 3 Transcriptional Inactivation.

BACKGROUND AND AIMS: NASH is an increasingly prevalent disease that is the major cause of liver dysfunction. Previous research has indicated that adipose cardiolipin synthase 1 (CRLS1) levels are associated with insulin sensitivity; however, the precise roles of CRLS1 and underlying mechanisms involving CRLS1 in the pathological process of NASH have not been elucidated. APPROACH AND RESULTS: Here, we discovered that CRLS1 was significantly down-regulated in genetically obese and diet-induced mice models. In vitro studies demonstrated that overexpression of CRLS1 markedly attenuated hepatic steatosis and inflammation in hepatocytes, whereas short hairpin RNA-mediated CRLS1 knockdown aggravated these abnormalities. Moreover, high-fat diet-induced insulin resistance and hepatic steatosis were significantly exacerbated in hepatocyte-specific Crls1-knockout (Crls1-HKO) mice. It is worth noting that Crls1 depletion significantly aggravated high-fat and high-cholesterol diet-induced inflammatory response and fibrosis during NASH development. RNA-sequencing analysis systematically demonstrated a prominently aggravated lipid metabolism disorder in which inflammation and fibrosis resulted from Crls1 deficiency. Mechanically, activating transcription factor 3 (ATF3) was identified as the key differentially expressed gene in Crls1-HKO mice through transcriptomic analysis, and our investigation further showed that CRLS1 suppresses ATF3 expression and inhibits its activity in palmitic acid-stimulated hepatocytes, whereas ATF3 partially reverses lipid accumulation and inflammation inhibited by CRLS1 overexpression under metabolic stress. CONCLUSIONS: In conclusion, CRLS1 ameliorates insulin resistance, hepatic steatosis, inflammation, and fibrosis during the pathological process of NASH by inhibiting the expression and activity of ATF3.

The Synergistic Antitumor Effect of Tanshinone IIA Plus Adriamycin on Human Hepatocellular Carcinoma Xenograft in BALB/C Nude Mice and Their Influences on Cytochrome P450 CYP3A4 In Vivo.

OBJECTIVE: Hepatocellular carcinoma is one of the most common diseases that seriously threaten human life and health. In this study, we evaluated the inhibitory effect of tanshinone IIA (Tan IIA) combined with adriamycin (ADM) on human hepatocellular carcinoma and developed a platform to assess the function if Chinese herbal ingredients combined with chemotherapy drugs have synergistic antitumor effects in vivo. METHODS: Established animal model of human hepatocarcinoma HepG2 cell in nude mice. Mice were divided into model control group, Tan IIA group, ADM group, and Tan IIA + ADM group. The changes from general condition, weight, tumor volume, and inhibition rate were observed. The data were gathered from serum AST level and histopathological changes. The content and activity of cytochrome P450 were determined by spectrophotometric analysis. CYP3A4 protein expression was analyzed by western blotting. The binding model crystal structure of Tan IIA and ADM with pregnane X receptor (PXR) was evaluated by Discovery Studio 2.1. RESULTS: A combination of Tan IIA with ADM could improve life quality by relieving ADM toxicity, decreasing tumor volume, declining serum AST level, and improving liner pathological section in tumor-bearing mice. The inhibitory rates of Tan IIA, ADM, and cotreatment were 32.77%, 60.96%, and 73.18%, respectively. The Tan IIA group significantly enhanced the content of cytochrome b5, P450, and erythromycin-N-demethylase activity. CYP3A4 protein expression was enhanced obviously by the Tan IIA + ADM group. Virtual molecular docking showed that both Tan IIA and ADM could be stably docked with the same binding site of PXR but different interactions. CONCLUSIONS: Tan IIA in combination with ADM could improve the life quality in tumor-bearing mice and enhance the antitumor effect. The Tan IIA group increased the concentration of cytochrome P450 enzymes and activity. Combined Tan IIA with ADM could upregulate the CYP3A4 protein expression and make relevant interaction with protein PXR by virtual docking.