Association Between Serum Neurofilament Light Chain and Neurochemistry Deficits in Patients with Spinocerebellar Ataxia Type 3.

Extensive evidence supports the claim that the serum neurofilament light chain (sNfL) can be used as a biomarker to monitor disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. In this study, we performed a cross-sectional study to analyze the association between sNfL and brain metabolic changes in SCA3 patients. The severity of ataxia was assessed by using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The sNfL levels and brain metabolic changes, represented by N-acetyl aspartate (NAA)/creatine (Cr) and choline complex (Cho)/Cr ratios, were measured by a single-molecule array and proton magnetic resonance spectroscopy, respectively. In this cohort, we observed consistently elevated sNfL levels and reduced brain metabolites in the cerebellar hemispheres, dentate nucleus, and cerebellar vermis. However, this correlation was further validated in the cerebellar cortex after analysis using pairwise comparisons and a Bonferroni correction. Taken together, our results further confirmed that sNfL levels were increased in SCA3 patients and were negatively correlated with metabolic changes in the cerebellar cortex. Our data also support the idea that sNfL levels are a promising potential complementary biomarker for patients with SCA3.

The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs.

Adult stem cells must limit their rate of protein synthesis, but the underlying mechanisms remain largely unexplored. Differences in protein synthesis among hematopoietic stem cells (HSCs) and progenitor cells did not correlate with differences in proteasome activity, total RNA content, mRNA content, or cell division rate. However, adult HSCs had more hypophosphorylated eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP2 as compared with most other hematopoietic progenitors. Deficiency for 4E-BP1 and 4E-BP2 significantly increased global protein synthesis in HSCs, but not in other hematopoietic progenitors, and impaired their reconstituting activity, identifying a mechanism that promotes HSC maintenance by attenuating protein synthesis.

A win-win platform: Stabilized black phosphorous nanosheets loading gallium ions for enhancing the healing of bacterial-infected wounds through synergistic antibacterial approaches.

Bacterial infection is the most common complication in wound healing, highlighting an urgent need for the development of innovative antibacterial technologies and treatments to address the growing threats posed by bacterial infections. Black phosphorus nanosheets (BPNSs), as a promising two-dimensional nanomaterial, have been utilized in treating infected wounds. However, BP's limited stability restricts its application. In this study, we enhance BP's stability and its antibacterial properties by anchoring gallium ions (Ga3+) onto BP's surface, creating a novel antibacterial platform. This modification reduces BP's electron density and enhances its antibacterial capabilities through a synergistic effect. Under near-infrared (NIR) irradiation, the BP/Ga3+ combination exerts antibacterial effects via photothermal therapy (PTT) and photodynamic therapy (PDT), while also releasing Ga3+. The Ga3+ employ a 'Trojan horse strategy' to disrupt iron metabolism, significantly boosting the antibacterial efficacy of the complex. This innovative material offers a viable alternative to antibiotics and holds significant promise for treating infected wounds and aiding skin reconstruction.

Plasma metabolome identifies potential biomarkers of gastric precancerous lesions and gastric cancer risk.

OBJECTIVES: Currently, metabolic biomarkers with great practicability of gastric cancer (GC) and gastric precancerous lesions (GPL) are scarce. Thus, we are devoted to determining the plasma metabolic profiles of patients with GPL or GC and validate candidate biomarkers for disease diagnosis. METHODS: In this hospital-based case-control study, 68 plasma samples from 27 non-atrophic gastritis (NAG, control), 31 GPL, and 10 GC patients were collected for targeted metabolomics analysis. Univariate and multivariate analyses were used for selecting the differential metabolites. A receiver operating characteristic curve combined with binary logistic regression analysis was performed to test the diagnostic performance of the differential metabolites. Dietary data were obtained using a semiquantitative food frequency questionnaire. RESULTS: Distinct metabolomic profiles were noted for NAG, GPL, and GC. Compared to the NAG patients, the levels of 5 metabolites in the GPL group and 4 metabolites in the GC group were found to significantly elevate. Compared with the model involving 9 traditional risk factors (AUC: 0.89, 95%CI: 0.78-1.00), Trimethylamine N-oxide, the most significant metabolite (P = 2.00 × 10-5, FDR = 0.003, FC > 2, VIP > 2), showed a good diagnostic performance for the patients with GC (AUC: 0.90, 95%CI: 0.78-1.00), and its diagnostic performance has been further improved with the integration of Rhamnose (AUC: 0.96, 95%CI: 0.89-1.00). CONCLUSION: In our study, 9 defined metabolites might serve as meaningful biomarkers for identifying the high-risk population of GPL and GC, possibly enhancing the prevention and control of GPL and GC.

Stereoconvergent Synthesis of Monofluoroalkenes via Photoinduced Dual Decarboxylative Cross-Coupling of α-Fluoroacrylic Acids with Redox-Active Esters.

Herein, a new strategy for the synthesis of monofluoroalkenes via employing α-fluoroacrylic acids and N-hydroxyphthalimide (NHPI) redox-active esters as coupling partners has been developed. This decarboxylative reaction enabled the formation of C(sp2)-C(sp3) bonds to provide a practical and efficient approach for the construction of a variety of monofluoroalkenes, which are key structural motifs in organic chemistry, under mild reaction conditions. The protocol exhibited excellent functional group compatibility and delivered monofluoroalkene products with excellent Z-stereoselectivity. This work also provides a platform for the modification of complex biologically active molecules containing carboxylic acids.

Circulating cell-free circRNA panel predicted tumorigenesis and development of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is reported with high morbidity and mortality. Currently, the sensitivity of diagnostic markers for colorectal cancer is low. Therefore, further exploration of new plasma diagnostic markers for early detection of colorectal cancer is of great value. We aimed to explore potential circRNAs in plasma as biomarkers for early diagnosis of CRC. METHODS: We employed the circRNA microarray to investigate dysregulated circRNAs in plasma samples of CRC patients, colorectal adenoma patients (CRA), and healthy controls. Through in-depth analysis, significantly differentially expressed circRNAs were screened as candidate targets. RESULTS: Eight circRNAs (hsa_circ_104885, hsa_circ_100185, hsa_circ_103171, hsa_circ_001978, hsa_circ_105039, hsa_circ_103627, hsa_circ_101717, and hsa_circ_104192) were obtained as candidate circRNAs with upregulation in CRC comparing with both CRA and healthy control. Through detecting the plasma expression levels of eight candidate targets, we identified three circRNA (hsa_circ_001978, hsa_circ_105039, and hsa_circ_103627) with increased level which were consistent with the microarray results in training set. Further validation found the circRNA panel was consistent with training set. The ROC curve also revealed a high diagnostic ability of hsa_circ_001978, hsa_circ_105039, and hsa_circ_103627 in predicted the CRC from CRA patients (AUC = 0.966) as well as healthy controls (AUC = 0.969). CONCLUSION: Our data suggest that hsa_circ_001978, hsa_circ_105039, and hsa_circ_103627 might be a CRC-specific biomarker for early diagnosis.

Retrospective analysis of deformed complex vertebral osteotomy in children with severe thoracic post-tubercular angular kyphosis.

BACKGROUND: Many surgical options have been described to manage post-tubercular kyphosis, but the standard approach for treating severe post-tubercular angular kyphosis in children has not been established yet. The present study was performed to evaluate the safety and efficacy of deformed complex vertebral osteotomy (DCVO) for the treatment of severe thoracic post-tubercular angular kyphosis (> 70°) in children. METHODS: Deformed complex vertebrae indicated that multiple deformed and fused vertebrae were usually involved with two or more vertebral bodies and the partial or total fusion of many segments' facet joints and intervertebral discs. Thus, DCVO indicated that a wider posterior wedge-shaped and three-column osteotomy was performed within deformed complex vertebrae to correct a more extensive range of angles. From 2010 to 2017, 15 children who suffered from severe thoracic post-tubercular angular kyphosis underwent DCVO. Deformed complex vertebrae involved two vertebral bodies in 9 patients and three vertebral bodies in 6 patients. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were assessed preoperatively and at the final follow up. This was a retrospective study analysing the outcome after grade 4/5 spinal osteotomies in deformed complex vertebrae. RESULTS: The mean duration of surgery was 239 ± 37.81 min. The average period of follow-up was 31.6 ± 6.98 months. The preoperative mean kyphosis of deformed complex vertebrae was 83.39° ± 9.04°; the mean thoracic kyphosis (TK) and lumbar lordosis (LL) were 81.09° ± 8.51° and 80.51° ± 7.64°, respectively; the mean sagittal vertical axis (SVA) was 3.83 cm ± 1.43 cm. The postoperative mean kyphosis of deformed complex vertebrae was reduced to 19.98° ± 2.47° (P < 0.001) with a mean kyphosis correction of 63.41°; at the final follow up, it was 18.4° ± 2.29° (P < 0.001) without obvious loss of correction. The postoperative mean TK, LL, and SVA were reduced to 24.05° ± 3.84°, 46.9° ± 3.53°, and 0.6 cm ± 0.34 cm, respectively (P < 0.001 for all); and there was no obvious loss of sagittal alignment and balance at the final follow up (p = 0.982, p = 0.604, p = 0.754). Complicated with neural dysfunction preoperatively, 5 Frankel's grade D cases showed complete neurological recovery at final follow up. VAS score reduced from 3.6 ± 1.18 to 0.87 ± 0.64 (P < 0.001); and ODI score reduced from 22.21 ± 6.93 to 5.02 ± 2.6 (P < 0.001) at the final follow up. CONCLUSIONS: DCVO was an individualized osteotomy for treating severe thoracic post-tubercular angular kyphosis in children and could be safe and effective in reducing the incidence of complications and significantly improving kyphosis correction.

Leonurine exerts a protective effect in dextran sodium sulfate-induced experimental inflammatory bowel disease mice model.

Inflammatory bowel disease (IBD) is a common chronic inflammatory gastrointestinal disease. The therapeutic strategies of IBD are limited. IBD mouse models were established by administering 4% dextran sodium sulfate (DSS), which were further treated with Leonurine (7.5, 15, 30 mg/kg). The disease phenotypes, cell apoptosis, inflammation factors and oxidative stress related chemicals were evaluated. In addition, the potential related mechanism was also explored. Consequently, Leonurine ameliorated IBD-associated disease phenotypes and increase colon lengths and inhibited intestinal cell apoptosis in DSS-induced IBD mice. In addition, Leonurine reduced the expression of inflammation factors and oxidative stress level in DSS-induced IBD mice. Finally, Leonurine inhibited TLR4/NF-κB signaling pathway and activated of Nrf2/HO-1 signaling pathway. Leonurine can ameliorate IBD-induced apoptosis, inflammation response and oxidative stress via the activation of Nrf2/HO-1 signaling pathway and suppression of TLR4/ NF-κB pathway.

One-pot green preparation of deep-ultraviolet and dual-emission carbon nanodots for dual-channel ratiometric determination of polyphenol in tea sample.

A novel deep-ultraviolet and dual-emission carbon nanodots (DUCDs)-based dual-channel ratiometric probe was prepared by a one-pot environmental-friendly hydrothermal process using guanidine as the only starting material for sensing polyphenol in tea sample (TPPs). Under the exposure to TPPs, the DUCDs not only provided a characteristic colorimetric response to TPPs, but also displayed TPPs-sensitive ratiometric fluorescence quenching. The detection mechanism was proved to be that enrichment-specific hydroxyl sites (e.g., -NH2 and -COOH) of DUCDs can specifically react with phenolic hydroxyl groups of TPPs to generate dynamic amide and carboxylate bonds by dehydration and/or condensation reaction. As a result, a new carbon nanomaterial with decrement of surface passivation groups, inherent light-absorbing, and invalid fluorescence emission was generated. The ratio (FL297nm/FL395nm) of fluorescence intensity at 297 nm and 395 nm of DUCDs excited at 275 nm decreased with increasing TPPs concentration. The linearity range was 5.0 ng/mL to 100 µg/mL with a detection limit (DL) of 3.5 ± 0.04 ng/mL for TPPs (n = 3, 3σ/k). Colorimetry of DUCDs, best measured as absorbance at 320 nm, was increased linearly in the TPP concentration range 200 ng/mL-200 µg/mL with a DL of 94.7 ± 0.04 ng/mL (n = 3, 3σ/k). The probe was successfully applied to the determination of TPPs in real tea samples, showing potential application prospects in food analysis.

Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study.

BACKGROUND: Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population. METHODS: A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers. RESULTS: After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36-1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50-1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76-1.17). A nonlinear dose-response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (all Pinteraction < 0.05). CONCLUSIONS: High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.

Dual Nickel/Ruthenium Strategy for Photoinduced Decarboxylative Cross-Coupling of α,ß-Unsaturated Carboxylic Acids with Cycloketone Oxime Esters.

Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,ß-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,ß-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.

Ratiometric detection of p-nitrophenol and its derivatives using a dual-emissive neuron cell-like carbonized probe based on a ππ stacking quenching mechanism.

p-Nitrophenol and its derivatives can cause serious harm to the health of mankind and the earth's ecosystem. Therefore, it is necessary to develop a novel and rapid detection technology for p-nitrophenol and its derivative. Herein, excellent water-soluble, large-size and dual-emissive neuron cell-analogous carbon-based probes (NCNPs) have been prepared via a solvothermal approach, using o-phenylenediamine as the only precursor, which exhibit two distinctive fluorescence (FL) peaks at 420 and 555 nm under 345 nm excitation. The NCNPs show a neuron cell-like branched structure, are cross-connected, and are in the range of 10-20 nm in skeleton diameter. Interestingly, their blue-green dual-colour fluorescence is quenched by p-nitrophenol or its derivative due to the specific mechanism of the ππ stacking interactions or internal filtration effect. Accordingly, a simple, rapid, direct and free-label ratiometric FL detection of p-nitrophenol is proposed. An excellent linear relationship shows linear regions over the range of 0.1-50 µM between the ratio of the FL intensity (FL555 nm/FL420 nm) and the concentrations of p-nitrophenol. The detection limit is as low as 43 nM (3σ). Importantly, the NCNP-based probe also shows acceptable repeatability and reproducibility for the detection of p-nitrophenol and its derivatives, and the recovery results for p-nitrophenol in real wastewater samples are favourable.

In vitro antifungal activities, molecular docking, and DFT studies of 4-amine-3-hydrazino-5-mercapto-1,2,4-triazole derivatives.

Six disubstituted Schiff base compounds were synthesized (A1-A6) and characterized using infrared spectroscopy (IR), elemental analyses (EA), 1H NMR, 13C NMR and HRMS spectroscopic techniques. Crystal structure of A1 has been determined by single crystal X-ray diffraction. The antifungal activities against three fungi were assessed, and the results showed that compounds of A1 and A2 have good activity for Wheat gibberellic with EC50 value of 15.89 and 16.99 mg/L, respectively. Compounds of A3, A4 and A6 have good bioactivity against Maize rough bacteria (the value of EC50 is 8.23, 7.56 and 7.92 mg/L, respectively). According to the result of molecular docking, compounds of A1 and A2 have the smallest docking energy (-8.33, -9.00 kcal/mol). Besides, for A1 and A2, the analysis of highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) analysis and molecular electrostatic potential map were to further elaborate the reason for the good activity with density functional theory (DFT)-B3LYP/6-31G.

Dietary inflammatory index and incidence of and death from primary liver cancer: A prospective study of 103,902 American adults.

Chronic inflammation plays an important role in primary liver cancer (PLC) etiology and can be influenced by dietary habits. No prospective study has investigated the association of dietary inflammatory index (DII) with PLC incidence and mortality. Therefore, we used prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to fill this gap. The DII was calculated from a validated 137-item food frequency questionnaire in a cohort of 103,902 individuals. Cox regression was used to estimate hazard ratios (HRs) for PLC incidence, and competing risk regression was used to estimate subdistribution HRs (SHRs) for PLC mortality. Restricted cubic spline regression was employed to identify the potential dose-response pattern. A total of 120 PLC cases and 102 PLC deaths were observed during follow-up. Higher DII scores from food and supplement were found to be associated with higher risks of developing PLC (HRTertile 3 vs. 1 2.05; 95% confidence interval [CI] 1.23-3.41) and death from this disease (SHRTertile 3 vs. 1 1.97; 95% CI 1.13-3.41). Similar results were obtained for DII score from food only. A nonlinear dose-response pattern was identified for the aforementioned associations (all pnonlinearity < 0.05). Overall, a more pro-inflammatory diet, as suggested by higher DII scores, is associated with higher risks of PLC incidence and mortality. These findings indicate that encouraging intake of more anti-inflammatory dietary components and reducing intake of pro-inflammatory components represent an attractive strategy to reduce PLC incidence and mortality.

Magnesium intake and primary liver cancer incidence and mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs. 1 : 0.44; 95% confidence interval: 0.24, 0.80; ptrend = 0.0065) and mortality (subdistribution hazard ratiotertile 3 vs. 1 : 0.37; 95% confidence interval: 0.19, 0.71; ptrend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose-response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all pnonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose-response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.

Posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis associated with split cord malformation.

BACKGROUND: Whether or not, prophylactic neurosurgical interventions of split cord malformation (SCM) before undertaking corrective surgery was the focus of debate. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis (RCS) associated with SCM. METHODS: From 2011 to 2017, 24 patients suffered from RCS associated with SCM underwent posterior-only surgical correction with heavy halo-femoral traction. The apex of the deformity was lumbar (n = 9), thoracic (n = 11), and thoracolumbar (n = 4). There were 13 cases of failure of segmentation; 4 cases of failure of formation and 7 cases of mixed defects. Based on SCM classification, there were 14 patients with SCM type 1 and 10 patients with SCM type 2. The Scoliosis Research Society (SRS)-22 and modified Japanese Orthopaedic Association (mJOA) scores were assessed preoperatively and at the final follow up. RESULTS: The mean duration of surgery was 327.08 ± 43.99 min and the mean blood loss was 1303.33 ± 526.86 ml. The mean follow-up period was 20.75 ± 8.29 months. The preoperative mean coronal Cobb angle was 80.38° ± 13.55°; on the bending radiograph of the convex side, the mean Cobb angle was 68.91° ± 15.48°; the mean flexibility was 15.04% ± 7.11%. After heavy halo-femoral traction, the mean coronal Cobb angle was reduced to 56.89° ± 13.39°. After posterior-only surgical correction, postoperative mean coronal Cobb angle was further reduced to 32.54° ±11.33°. The postoperative mean correction rate was 60.51% ± 7.79%. At the final follow up, the corrective loss rate of Cobb angle was only 3.17%. The SRS-22 total score improved at the final follow-up evaluation compared with the preoperative SRS-22 total score. The spinal cord function was stable and there were no new neurological symptoms after correction. There were no significant differences between final follow-up and preoperative mJOA total scores. CONCLUSIONS: Without prophylactic neurosurgical intervention and spine-shortening osteotomy, posterior-only surgical correction with heavy halo-femoral traction could be safe and effective for the treatment of RCS associated with SCM.

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo.

It has been reported that taxifolin inhibit osteoclastogenesis in RAW264.7 cells. In our research, the inhibition effects of taxifolin on the osteoclastogenesis of human bone marrow-derived macrophages (BMMs) induced by receptor activator of NF-κB ligand (RANKL) as well as the protection effects in lipopolysaccharide-induced bone lysis mouse model have been demonstrated. In vitro, taxifolin inhibited RANKL-induced osteoclast differentiation of human BMMs without cytotoxicity. Moreover, taxifolin significantly suppressed RANKL-induced gene expression, including tartrate-resistant acid phosphatase, matrix metalloproteinase-9 nuclear factor of activated T cells 1 and cathepsin K, and F-actin ring formation. Further studies showed that taxifolin inhibit osteoclastogenesis via the suppression of the NF-κB signaling pathway. In vivo, taxifolin prevented bone loss in mouse calvarial osteolysis model. In conclusion, the results suggested that taxifolin has a therapeutic potential for osteoclastogenesis-related diseases such as osteoporosis, osteolysis, and rheumatoid arthritis.

SIRT1 activator isolated from artificial gastric juice incubate of total saponins in stems and leaves of Panax ginseng.

Panax ginseng as a traditional Chinese medicine has been extensively used for the treatment of many diseases, especially in prolonging life and anti-tumor. Dammarane-type triterpenoids from P. ginseng have diverse beneficial effects and their chemical structures can be modified in the gastrointestinal tract after oral administration. In this paper, the dammarane-type triterpenoids were isolated from artificial gastric juice incubate of total saponins in the stems and leaves of P. ginseng through column chromatographic methods and their chemical structures were determined based on spectral data. Two new dammarane-type triterpenoids named ginsenotransmetins B (1) and C (2), along with twenty-nine known compounds (3-31), were obtained. All 31 compounds isolated were investigated for their activities of SIRT1 using SIRT1 fluorometric drug discovery assay kit. Among them, compounds 11, 17, 18, 20, 23, 24, 28, and 29, which were found to be potential as SIRT1 activators, exhibited significant stimulation of SIRT1 activity. The results showed that these compounds may be considered to be a useful medicinal resource for prolonging life and anti-tumor. In addition, the results were helpful to explain the longevity effect of ginseng from the new field of view.

Determination of the transformation of ginsenosides in Ginseng Radix et Rhizoma during decoction with water using ultra-fast liquid chromatography coupled with tandem mass spectrometry.

This study was conducted to determine the variations of ginsenosides in Ginseng Radix et Rhizoma when using different preparation solvents and explore the major factors for changes. With an established ultra-fast liquid chromatography coupled with tandem mass spectrometry method which could quantify 52 ginsenosides, the extraction differences were characterized and compared using different solvents (water, 70% aqueous ethanol, and ethanol). Subsequently, a series of aqueous solutions with different pH were prepared to test the influence of pH to the changes of ginsenosides. Meanwhile, acetic acid and aspartic acid were used to verify whether the reaction had a relationship with the kind of acids. After refluxing with water, not only highly polar ginsenosides were extracted, some less polar ginsenosides such as ginsenoside Rg3 , Rg5 , Rk1 , and Rh2 occurred or increased rapidly. Further experiments indicated that less polar ginsenosides were easier to generate at low pH values, and the reaction was only related to pH other than what kind of acids were used. It is the first time to elaborate the contents variation of 52 ginsenosides when using different extraction methods. The results indicated that decoction with water could enhance the transformation of highly polar ginsenosides to less polar ginsenosides and the process was pH dependent.

Taxifolin enhances osteogenic differentiation of human bone marrow mesenchymal stem cells partially via NF-κB pathway.

Taxifolin, a flavonoid compound, has been reported to stimulate osteogenic differentiation in osteoblasts. The present study investigated whether taxifolin affects the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and the molecular mechanisms involved. The proliferation and osteogenic differentiation of hBMSCs in the presence of taxifolin were examined by CCK-8 assay, alkaline phosphatase (ALP) activity, ALP staining and Alizarin red staining. The expression of osteogenic differentiation markers were detected by real-time quantitative PCR (RT-PCR) analysis and western blot assay. The activation of potential related pathways was examined by luciferase reporter assay, immunofluorescence and western blot analysis. Taxifolin treatment increased osteogenic differentiation of hBMSCs without cytotoxicity. Luciferase reporter assay showed that taxifolin could not activate estrogen receptor pathway, but inhibit TNF-α-induced NF-κB signaling pathway activation in osteogenic induction condition. Moreover, the nucleus translocation of NF-κB under TNF-α treatment was inhibited by taxifolin treatment. The taxifolin-induced osteogenic differentiation effects of hBMSCs were abolished by TNF-α treatment. In conclusion, our results suggested that taxifolin could promote osteogenesis of hBMSCs, partially through antagonism of NF-κB signaling pathway.