Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes Infection: A 12-Year Hospital-Based Study in Xi'an, China.

INTRODUCTION: Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. RESULTS: Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. CONCLUSIONS: When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Effects of stand ages on soil enzyme activities in Chinese fir plantations and natural secondary forests.

Forest type and stand age are important biological factors affecting soil enzyme activities. However, the changes in soil enzyme activities across stand ages and underlying mechanisms under the two forest restoration strate-gies of plantations and natural secondary forests remain elusive. In this study, we investigated the variations of four soil enzyme activities including cello-biohydrolase (CBH), ß-1,4-glucosidase (ßG), acid phosphatase (AP) and ß-1,4-N-acetylglucosaminidase (NAG), which were closely associated with soil carbon, nitrogen, and phosphorus cycling, across Cunninghamia lanceolata plantations and natural secondary forests (5, 8, 21, 27 and 40 years old). The results showed that soil enzyme activities showed different patterns across different forest types. The acti-vities of AP, ßG and CBH in the C. lanceolata plantations were significantly higher than those in the natural secon-dary forests, and there was no significant difference in the NAG activity. In the plantations, AP activity showed a decreasing tendency with the increasing stand ages, with the AP activity in the 5-year-old plantations significantly higher than other stand ages by more than 62.3%. The activities of NAG and CBH decreased first and then increased, and ßG enzyme activity fluctuated with the increasing stand age. In the natural secondary forests, NAG enzyme activity fluctuated with the increasing stand age, with that in the 8-year-old and 27-year-old stand ages being significantly higher than the other stand ages by more than 14.9%. ßG and CBH enzyme activities increased first and then decreased, and no significant difference was observed in the AP activity. Results of the stepwise regression analyses showed that soil predictors explained more than 34% of the variation in the best-fitting models predicting soil enzyme activities in the C. lanceolata plantations and natural secondary forests. In conclusion, there would be a risk of soil fertility degradation C. lanceolata plantations with the increasing stand age, while natural secondary forests were more conducive to maintaining soil fertility.

Effect of Reactive Oxygen Scavenger N,N'-Dimethylthiourea (DMTU) on Seed Germination and Radicle Elongation of Maize.

Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic stress may be mediated by hydrogen peroxide (H2O2). The effects of the ROS scavenger N,N'-dimethylthiourea (DMTU) on maize seed germination through endogenous H2O2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H2O2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H2O2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes (ZmAPX2 and ZmCAT2) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm-3 DMTU). We suggest the use of 200 mmol·dm-3 DMTU as an H2O2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.

Hepatic MR imaging using IDEAL-IQ sequence: Will Gd-EOB-DTPA interfere with reproductivity of fat fraction quantification?

BACKGROUND: Iterative decomposition of water and fat with echo asymmetry and least squares estimation quantification sequence (IDEAL-IQ) is based on chemical shift-based water and fat separation technique to get proton density fat fraction. Multiple studies have shown that using IDEAL-IQ to test the stability and repeatability of liver fat is acceptable and has high accuracy. AIM: To explore whether Gadoxetate Disodium (Gd-EOB-DTPA) interferes with the measurement of the hepatic fat content quantified with the IDEAL-IQ and to evaluate the robustness of this technique. METHODS: IDEAL-IQ was used to quantify the liver fat content at 3.0T in 65 patients injected with Gd-EOB-DTPA contrast. After injection, IDEAL-IQ was estimated four times, and the fat fraction (FF) and R2* were measured at the following time points: Pre-contrast, between the portal phase (70 s) and the late phase (180 s), the delayed phase (5 min) and the hepatobiliary phase (20 min). One-way repeated-measures analysis was conducted to evaluate the difference in the FFs between the four time points. Bland-Altman plots were adopted to assess the FF changes before and after injection of the contrast agent. P < 0.05 was considered statistically significant. RESULTS: The assessment of the FF at the four time points in the liver, spleen and spine showed no significant differences, and the measurements of hepatic FF yielded good consistency between T1 and T2 [95% confidence interval: -0.6768%, 0.6658%], T1 and T3 (-0.3900%, 0.3178%), and T1 and T4 (-0.3750%, 0.2825%). R2* of the liver, spleen and spine increased significantly after injection (P < 0.0001). CONCLUSION: Using the IDEAL-IQ sequence to measure the FF, we can obtain results that will not be affected by Gd-EOB-DTPA. The high reproducibility of the IDEAL-IQ sequence makes it available in the scanning interval to save time during multiphase examinations.

Quality appraisal of clinical practice guidelines for motor neuron diseases or related disorders using the AGREE II instrument.

Objectives: This study aimed to systematically assess the quality of CPGs for motor neuron diseases (MNDs) or related disorders and identify the gaps that limit evidence-based practice. Methods: Four scientific databases and six guideline repositories were searched for eligible CPGs. Three researchers assessed the eligible CPGs using the Appraisal of Guidelines Research and Evaluation II instrument. The distribution of the level of evidence and strength of recommendation of these CPGs were determined. The univariate regression analysis was used to explore the characteristic factors affecting the quality of CPGs. Results: Fifteen CPGs met the eligibility criteria: 10 were for MND and 5 were for spinal muscular atrophy. The mean overall rating score was 44.5%, and only 3 of 15 CPGs were of high quality. The domains that achieved low mean scores were applicability (24.4%), rigor of development (39.9%), and stakeholder involvement (40.3%). Most recommendations were based on low-quality evidence and had a weak strength. The CPGs that were updated, meant for adults, and evidence based, and used a CPG quality tool and a grading system were associated with higher scores in certain specific domains and overall rating. Conclusion: The overall quality of CPGs for MNDs or related disorders was poor and recommendations were largely based on low-quality evidence. Many areas still need improvement to develop high-quality CPGs, and the use of CPG quality tools should be emphasized. A great deal of research on MNDs or related disorders is still needed to fill the large evidence gap.

Proteomic analysis reveals that Polygonatum cyrtonema Hua polysaccharide ameliorates mice muscle atrophy in chemotherapy-induced cachexia.

Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.

Description of Limnobaculum eriocheiris sp. nov., an intestinal bacterium of Eriocheir sinensis, and reclassification of the genera Jinshanibacter and Insectihabitans as Limnobaculum.

A Gram-stain-negative, aerobic, non-motile and rod-shaped strain, designated LJY008T, was isolated from the intestinal of Eriocheir sinensis in Pukou base of Jiangsu Institute of Freshwater Fisheries. Strain LJY008T could grow at 4-37 â„ƒ (optimum, 30 â„ƒ), pH 6.0-8.0 (optimum, pH 7.0), and with 1.0-6.0% NaCl (w/v; optimum, 1.0%). Strain LJY008T shared highest 16S rRNA gene sequence similarity with Jinshanibacter zhutongyuii CF-458T (99.3%), followed by J. allomyrinae BWR-B9T (99.2%), Insectihabitans xujianqingii CF-1111T (97.3%), and Limnobaculum parvum HYN0051T (96.7%). The major polar lipids include phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The only respiratory quinone was Q8, and the main fatty acids (> 10%) were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), summed feature 8 (C18:1ω7c), and C14:0. The genome-based phylogenies showed that strain LJY008T was closely associated with members of the genus Jinshanibacter, Insectihabitans, and Limnobaculum. The average nucleotide identities and average amino acid identities (AAI) among strain LJY008T and closely related neighbours were all below 95%, and the digital DNA-DNA hybridization values among them were all below 36%. The genomic DNA G + C content of strain LJY008T was 46.1%. Based on the phenotypic, phylogenetic, biochemical and chemotaxonomic analysis, strain LJY008T represents a novel species of the genus Limnobaculum, for which the name Limnobaculum eriocheiris sp. nov. is proposed. The type strain is LJY008T (= JCM 34675T = GDMCC 1.2436T = MCCC 1K06016T). In addition, the genera Jinshanibacter and Insectihabitans were reclassified as Limnobaculum, because there was no significant genome-scale divergence or diagnosable difference on phenotypic and chemotaxonomic traits, such as strains of Jinshanibacter and Insectihabitans sharing AAI values of 93.88-94.96%.

Establishment and application of a high-throughput screening model for cell adhesion inhibitors.

The cell adhesion between leukocytes and endothelial cells plays an important balanced role in the pathophysiological function, while excessive adhesion caused by etiological agents is associated with the occurrence and development of many acute and chronic diseases. Cell adhesion inhibitors have been shown to have a potential therapeutic effect on these diseases, therefore, efficient and specific inhibitors against cell adhesion are highly desirable. Here, using lipopolysaccharide-induced human umbilical vein endothelial cells (HUVECs) and calcein-AM-labeled human monocytic cell THP-1, we established a high-throughput screening model for cell adhesion inhibitors with excellent model evaluation parameters. Using the drug repurposing strategy, we screened out lifitegrast, a potent cell adhesion inhibitor, which inhibited cell adhesion between HUVEC and THP-1 cells by directly interrupting the adhesion interaction between HUVEC and THP-1 cells and showed a strong therapeutic effect on the mouse acute liver injury induced by poly (I:C)/D-GalN. Therefore, the screening model is suitable for screening and validating cell adhesion inhibitors, which will promote the research and development of inhibitors for the treatment of diseases caused by excessive cell adhesion.

Trusted-Data-Guided Label Enhancement on Noisy Labels.

Label distribution covers a certain number of labels, representing the degree to which each label describes the instance. Label enhancement (LE) is a procedure of recovering the label distribution from the logical labels in the training data, the purpose of which is to better depict the label ambiguity through label distribution. However, data annotation inevitably introduces label noise, and it is extremely challenging to implement LE on corrupted labels. To deal with this problem, one way to recover the label distribution from the corrupted labels is to be guided by a small batch of trusted data. In this article, a novel LE method named TALEN is proposed via recovering and progressively refining label distribution guided by trusted data. Specifically, an LE process is applied to the untrusted data to select samples with a clean label. In addition, a combined loss function is designed to train the predictive model for classification. Experiments on datasets with synthetic label noise validate the feasibility of identifying clean labels via the recovered label distribution. Furthermore, experimental results on both synthetic label noise and real-world label noise on image datasets and additional experiments on text datasets show a clear advantage of TALEN over several existing noise-robust learning methods.

Family socioeconomic status and mental health in Chinese adolescents: the multiple mediating role of social relationships.

BACKGROUND: The purpose of this study is to explore whether social relationships of family and school contexts mediate the influence of socioeconomic status (SES) on Chinese adolescents' mental health. METHODS: A school-based study was conducted among a sample aged 13-18 in East China (n = 6902). We used scales for measuring social relationships and self-rated mental health. Family SES was computed from subjective socioeconomic status, education and occupation of parents.The mediation model was tested by using Path Analysis in IBM SPSS-Amos. RESULTS: The results showed that SES can significantly influence adolescent mental health through parent-child relationship, student-teacher relationship and student-student relationship. The total effect, direct effect and total indirect effect were -0.209 (95% CI = -0.299, -0.136), -0.090 (95% CI = -0.174, -0.007), -0.119 (95% CI = -0.187, -0.078) for boys, and -0.337 (95% CI = -0.478, -0.230), -0.132 (95% CI = -0.283, 0.010), -0.205 (95% CI = -0.351, -0.085) for girls. CONCLUSION: The link between SES and adolescent mental health can be explained by social relationships. Focusing on the parent-child, student-student and student-teacher relationship interventions may contribute to improving the mental health of Chinese adolescents, especially in low socioeconomic groups, as well as female students.

Lean body mass predicts postoperative liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. OBJECTIVE: We aimed to assess the association between LBM and PHLF in HCC patients. METHODS: PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. RESULTS: The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p< 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172-0.957, p= 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (ptrend< 0.001). CONCLUSIONS: LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed.

GBP2 as a potential prognostic predictor with immune-related characteristics in glioma.

Guanylate binding protein 2 (GBP2) is a member of the guanine binding protein family, and its relationship with prognostic outcomes and tumor immune microenvironments in glioma remains elusive. We found GBP2 were increased in glioma tissues at both mRNA and protein levels. Kaplan-Meier curves revealed that high GBP2 expression was linked with worse survival of glioma patients, and multivariate Cox regression analysis indicated that high GBP2 expression was an independent prognostic factor for glioma. Combined analysis in immune database revealed that the expression of GBP2 was significantly related to the level of immune infiltration and immunomodulators. Single-cell analysis illustrated the high expression of GBP2 in malignant glioma cells showed the high antigen presentation capability, which were confirmed by real-time polymerase chain reaction (qRT-PCR) data. Additionally, the hsa-mir-26b-5p and hsa-mir-335-5p were predicted as GBP2 regulators and were validated in U87 and U251 cells. Our results first decipher immune-related characteristics and noncoding regulators of GBP2 in glioma, which may provide insights into associated immunotherapies and prognostic predictor.

LC-MS Metabolite Profiling and the Hypoglycemic Activity of Morus alba L. Extracts.

Morus alba L. is used in traditional Chinese medicine for its anti-diabetic activity; however, the part of the hypoglycemic activity and related active metabolites are still not fully clarified. In this study, the metabolites in the M. alba roots, leaves, twigs, and fruits extracts (70% ethanol extracts) were systematically identified, and their hypoglycemic activity was evaluated by the high-fat diet/streptozotocin-induced 2 diabetes mellitus (T2D) mouse model. A total of 60 high-level compounds, including 16 polyphenols, 43 flavonoids, and one quinic acid, were identified by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with the fragmentation pathways of standards and the self-established database. Among them, 23 metabolites were reported for the first time from this plant. In contrast to the extracts of M. alba leaves and fruits, the extracts of roots and twigs displayed significant hypoglycemic activity The glycemia was significantly reduced from 32.08 ± 1.27 to 20.88 ± 1.82 mmol/L and from 33.32 ± 1.98 to 24.74 ± 1.02 mmol/L, respectively, after 4 weeks of treatment with roots and twigs extracts. Compound 46 (morusin), which is a high-level component identified from the extracts of M. alba roots, also displayed significant activity in decreasing the blood glucose level of T2D mice reduced from 31.45 ± 1.23 to 23.45 ± 2.13 mmol/L. In addition, the extracts of roots and twigs displayed significant activity in reducing postprandial glycemia. This work marks the first comparison of the metabolites and hypoglycemic activity of M. alba roots, leaves, twigs, and fruits extracts, and provides a foundation for further development of M. alba extracts as anti-diabetic drugs.

Natural borneol enhances the anti-cerebral ischaemia efficacy of formononetin in MCAO/R rats by promoting its delivery in the brain.

Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery. Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol's promoting formononetin delivery in the brain. Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol. Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs.

Aestuariicella albida sp. nov., isolated from surface water of the Yellow Sea, and proposal of the genus Aestuariicella as a member of the family Cellvibrionaceae.

A Gram-stain-negative, non-motile and aerobic bacterium, designated HHU G3-2T, was isolated from surface water of the Yellow Sea, PR China. Strain HHU G3-2T was positive for oxidase activity and negative for catalase. Optimal growth occurred at 28 °C (range, 20-37 °C), pH 7.0 (range, pH 6.0-9.0) and in the presence of 2-5 % (w/v) NaCl (range, 1-7%). Phylogenetic analysis based on 16S rRNA gene sequences and 120 ubiquitous single-copy protein-coding genes indicated that strain HHU G3-2T formed a distinct phylogenetic lineage with Aestuariicella hydrocarbonica JCM 30134T, sharing a 16S rRNA gene sequence similarity of 98.05%. Average nucleotide identity and digital DNA-DNA hybridization values between strain HHU G3-2T and A. hydrocarbonica JCM 30134T were 75.74 and 17.80%, respectively, which were below the threshold values of 95-96 and 70 %, respectively. The DNA G+C content of the genomic DNA was 51.17 mol%. The major fatty acids (>10 %) were C17 : 1 ω8c (19.8 %), summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c; 15.9 %), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c; 13.8 %) and C17 : 0 (10.3 %). The predominant isoprenoid quinone was ubiquinone-8. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on the polyphasic taxonomic data, strain HHU G3-2T represents a novel species of the genus Aestuariicella, for which the name Aestuariicella albida sp. nov. is proposed. The type strain is HHU G3-2T (=MCCC 1K04224T=JCM 34652T=GDMCC 1.2418T=CGMCC 1.17397T). In addition, we proposed the genus Aestuariicella as a member of the family Cellvibrionaceae.

Danggui Niantong granules ameliorate rheumatoid arthritis by regulating intestinal flora and promoting mitochondrial apoptosis.

CONTEXT: Danggui Niantong Granules (DGNTG) are a valid and reliable traditional herbal formula, commonly used in clinical practice to treat rheumatoid arthritis (RA). However, the mechanism of its effect on RA remains unclear. OBJECTIVE: An investigation of the therapeutic effects of DGNTG on RA. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into four groups: control, model, DGNTG (2.16 g/kg, gavage), methotrexate (MTX) (1.35 mg/kg, gavage) for 28 days. The morphology of synovial and ankle tissues was observed by haematoxylin-eosin staining. The responses of mitochondrial apoptosis were assessed by qPCR, Western blotting and immunohistochemical staining. Rat faeces were analysed by 16S rRNA sequencing. RESULTS: Our results showed that DGNTG treatment reduced AI scores (7.83 ± 0.37 vs. 4.67 ± 0.47, p < 0.01) and paw volumes (7.63 ± 0.17 vs. 6.13 ± 0.11, p < 0.01) compared with the model group. DGNTG also increased the expression of Bax (0.34 ± 0.03 vs. 0.73 ± 0.03, p < 0.01), cytochrome c (CYTC) (0.24 ± 0.02 vs. 0.64 ± 0.01, p < 0.01) and cleaved caspase-9 (0.24 ± 0.04 vs. 0.83 ± 0.08, p < 0.01), and decreased bcl-2 (1.70 ± 0.11 vs. 0.60 ± 0.09, p < 0.01) expression. DGNTG treatment regulated the structure of gut microbiota. DISCUSSION AND CONCLUSIONS: DGNTG ameliorated RA by promoting mitochondrial apoptosis, which may be associated with regulating gut microbiota structure. DGNTG can be used as a supplement and alternative drug for the treatment of RA; its ability to prevent RA deserves further study.

Gerberdriasins A-F, six undescribed coumarin derivatives from Gerbera anandria (Linn) Sch-Bip and their protective effects on scopolamine-induced injury in PC12 cells.

A chemical investigation on the herb Gerbera anandria (Linn) Sch-Bip led to the isolation and identification of six previously undescribed coumarin derivatives, named Gerberdriasins A-F (1-6). Structurally, their chemical structures and absolute configurations were determined by nuclear magnetic resonance (1D and 2D NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), experimental and quantum mechanical nuclear magnetic resonance (QM-NMR) methods, Mosher's method and calculated electronic circular dichroism (ECD) experiments. The biological activity of the obtained compounds showed that they displayed significant neuroprotective effects against scopolamine-induced injury in PC12 cells at the concentrations 12.5, 25.0 and 50.0 nM. Further study demonstrated that 1 could inhibit cell apoptosis, decrease malondialdehyde (MDA) levels and increase superoxide dismutase (SOD) activity in scopolamine-treated PC12 cells.

Adsorption of thiotepa anticancer drugs on the C3N nanotube as promising nanocarriers for drug delivery.

This paper focused on the efficiency of carbon nitride nanotubes functionalized with alanine amino acid (f-C3NNTs) in thiotepa (TPA) anti-cancerous drug delivery via density functional theory (DFT). Pristine C3NNTs were incorporated for comparison. TPA was found to spontaneously undergo exothermic adsorption onto the nanostructures. The f-C3NNT/TPA complexes showed the highest interaction strength. The adsorption distance of TPA was found to be smaller, with a greater adsorption capacity and solubility on the f-C3NNT surface than on the pristine C3NNT surface. As they were polar, all the complexes were concluded to be insoluble within an aqueous phase. The quantum molecular descriptors revealed the f-C3NNT nanocarriers to be more reactive than the C3NNT carrier. The drug was found to spontaneously and exothermically interact with f-C3NNT. As a result, f-C3NNT would be promising for TPA adsorption in drug delivery applications.

Vlasouliodes A-D, four new C30 dimeric sesquiterpenes exhibiting potential inhibition of MCF-7 cells from Vladimiria souliei.

As our ongoing interest to search bioactive dimeric sesquiterpenes from the genus Vladimiria (Asteraceae), the plant of Vladimiria souliei was studied. Based on the repetitive chromatographic fractionation, a chemical investigation on the roots of Vladimiria souliei led to the isolation and the identification of four previously undescribed sesquiterpene dimers, vlasouliodes A-D (1-4). Their chemical structures were elucidated by comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR spectroscopic data. The absolute configurations of them were unambiguously established by the experimental and calculated ECD data. In the in vitro biological activity evaluation, 1 and 3 displayed pronounced inhibitory activity against human breast adenocarcinoma cell lines (MCF-7) with IC50 values of 17.12 ± 0.42 µM and 13.12 ± 0.10 µM, respectively. Additionally, treatment with 1 and 3 induced cell apoptosis in MCF-7 cells, down-regulated the expression of Caspase-3 and up-regulated the expression of Cleaved-caspase-3.