Cementum protein 1 gene-modified adipose-derived mesenchymal stem cell sheets enhance periodontal regeneration in osteoporosis rat.

BACKGROUND AND OBJECTIVES: Osteoporosis (OP) and periodontitis are both diseases with excessive bone resorption, and the number of patients who suffer from these diseases is expected to increase. OP has been identified as a risk factor that accelerates the pathological process of periodontitis. Achieving effective and safe periodontal regeneration in OP patients is a meaningful challenge. This study aimed to assess the efficacy and biosecurity of human cementum protein 1 (hCEMP1) gene-modified cell sheets for periodontal fenestration defect regeneration in an OP rat model. MATERIALS AND METHODS: Rat adipose-derived mesenchymal stem cells (rADSCs) were isolated from Sprague-Dawley rats. After primary culture, rADSCs were subjected to cell surface analysis and multi-differentiation assay. And rADSCs were transduced with hCEMP1 by lentiviral vector, and hCEMP1 gene-modified cell sheets were generated. The expression of hCEMP1 was evaluated by reverse transcription polymerase chain reaction and immunocytochemistry staining, and transduced cell proliferation was evaluated by Cell Counting Kit-8. The hCEMP1 gene-modified cell sheet structure was detected by histological analysis and scanning electron microscopy. Osteogenic and cementogenic-associated gene expression was evaluated by real-time quantitative polymerase chain reaction. In addition, an OP rat periodontal fenestration defect model was used to evaluate the regeneration effect of hCEMP1 gene-modified rADSC sheets. The efficacy was assessed with microcomputed tomography and histology, and the biosecurity of gene-modified cell sheets was evaluated by histological analysis of the spleen, liver, kidney and lung. RESULTS: The rADSCs showed a phenotype of mesenchymal stem cells and possessed multi-differentiation capacity. The gene and protein expression of hCEMP1 through lentiviral transduction was confirmed, and there was no significant effect on rADSC proliferation. Overexpression of hCEMP1 upregulated osteogenic and cementogenic-related genes such as runt-related transcription factor 2, bone morphogenetic protein 2, secreted phosphoprotein 1 and cementum attachment protein in the gene-modified cell sheets. The fenestration lesions in OP rats treated with hCEMP1 gene-modified cell sheets exhibited complete bone bridging, cementum and periodontal ligament formation. Furthermore, histological sections of the spleen, liver, kidney and lung showed no evident pathological damage. CONCLUSION: This pilot study demonstrates that hCEMP1 gene-modified rADSC sheets have a marked ability to enhance periodontal regeneration in OP rats. Thus, this approach may represent an effective and safe strategy for periodontal disease patients with OP.

Dynamics of TRF1 organizing a single human telomere.

Chromosome stability is primarily determined by telomere length. TRF1 is the core subunit of shelterin that plays a critical role in telomere organization and replication. However, the dynamics of TRF1 in scenarios of telomere-processing activities remain elusive. Using single-molecule magnetic tweezers, we here investigated the dynamics of TRF1 upon organizing a human telomere and the protein-DNA interactions at a moving telomeric fork. We first developed a method to obtain telomeres from human cells for directly measuring the telomere length by single-molecule force spectroscopy. Next, we examined the compaction and decompaction of a telomere by TRF1 dimers. TRF1 dissociates from a compacted telomere with heterogenous loops in ∼20 s. We also found a negative correlation between the number of telomeric loops and loop sizes. We further characterized the dynamics of TRF1 at a telomeric DNA fork. With binding energies of 11 kBT, TRF1 can modulate the forward and backward steps of DNA fork movements by 2-9 s at a critical force of F1/2, temporarily maintaining the telomeric fork open. Our results shed light on the mechanisms of how TRF1 organizes human telomeres and facilitates the efficient replication of telomeric DNA. Our work will help future research on the chemical biology of telomeres and shelterin-targeted drug discovery.

Repeatability of i.Profiler for measuring wavefront aberrations in healthy eyes.

PURPOSE: To evaluate the repeatability of wavefront aberration measurements and the correlation between corneal aberration and pupil size in normal eyes using a wavefront-based autorefractor (i.ProfilerPlus; Carl Zeiss Vision, Germany). METHODS: A prospective cross-sectional study. Wavefront aberrations, including spherical aberration (SA) (Z40), coma (Z3-1, Z31), trefoil (Z3-3, Z33) and total higher-order aberrations (tHOA), were measured at different pupil diameters. The repeatability was evaluated using one-way ANOVA method, and statistical indicators including within-subject standard deviation (Sw), test-retest repeatability (TRT), and intra-class correlation coefficient (ICC). The correlations between corneal aberrations and pupil sizes were evaluated by Pearson correlation analysis. RESULTS: A total of 96 healthy young volunteers were enrolled. Corneal and ocular higher-order aberrations (HOA) measured by i.Profiler showed Sw < 0.01 µm, TRT < 0.10 µm, ICC > 0.90. There was a linear positive correlation between the corneal HOA and pupil size. The correlation coefficient between SA and tHOA was the largest (r = 0.996, P < 0.001). CONCLUSIONS: The measurements of wavefront aberrations by i.Profiler are highly repeatable. Corneal HOA was significantly dependent on pupil size. SA was the most influential aberration for visual quality in this study.

Nurses' voice behaviour: The influence of humble leadership, affective commitment and job embeddedness in China.

AIM: To test the influence of humble leadership, job embeddedness and affective commitment on the voice behaviour of nurses. BACKGROUND: A nurse's voice behaviour is regarded as an important measure to identify and solve problems in medical institutions, and improve patients' satisfaction. It is urgent to pay sufficient attention to nurses' advice to determine which factors can stimulate enthusiasm in this area. METHODS: This study is a cross-sectional study involving 598 nurses. RESULTS: The results showed that humble leadership, job embeddedness, affective commitment and voice behaviour were significantly positively correlated. Job embeddedness played a partial mediating role in humble leadership and affective commitment; meanwhile, affective commitment also partially mediated the influence of job embeddedness on voice behaviour. CONCLUSIONS: Humble leadership was the key to improve the voice behaviour of nurses; as a mediating mechanism, job embeddedness and affective commitment further explained how humble leadership promoted the voice behaviour of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: The effects of humble leadership, job embeddedness and affective commitment to voice behaviour could be used to guide the management of clinical nurses. In particular, the humble leadership style perceived by nurses and the enhanced emotional connection with the organisation would contribute to the generation of voice behaviour.

The risk of moderate-to-severe post-operative pain following the placement of dental implants.

In recent years, the implant-supported dentures have risen rapidly, and thus, more attention was paid to post-operative pain, following dental implantation. To explore risk factors and establish as well as validate a risk prediction model for moderate-to-severe post-operative pain following dental implantation. A observational study of 352 patients with 563 implants was carried out. The following candidate predictors were collected: age, gender, pain sensitivity, anxiety, pain expectation, operator experience, position, length and number of placed implants, duration of surgery and surgery procedures. The outcome was the presence of moderate-to-severe post-operative pain within the 24 hours post-surgery. Multivariate logistic regression in combination with bootstrapping techniques was used to explore independent risk factors and establish a prediction model. The mean pain intensity score was 4.21 within 24 hours post-operatively, while the incidence of moderate-to-severe pain was 61.9%. Independent risk factors of moderate-to-severe post-operative pain were flap surgery, surgical template, the interaction between anxiety state and pain sensitivity, the interaction between pain sensitivity and pain expectation and the interaction between implant length and immediate implant. The area under the receiver operator characteristic curve was 0.72. The model's sensitivity was 75.7%, and the specificity was 64.2%. The model reliability was good (Nagelkerke's R2 0.226). The risk factors and the prediction model (needs further improvement) can help dentists to identify patients at increased risk of moderate-to-severe post-operative pain following dental implantation.

Dynamic changes of peri-implant soft tissue after interim restoration removal during a digital intraoral scan.

STATEMENT OF PROBLEM: During a digital intraoral scan for an esthetic implant restoration, the peri-implant soft tissue will collapse rapidly after the interim restoration (IR) is removed, making it difficult to replicate the established emergence profile. The rate of this collapse is unclear. PURPOSE: The purpose of this clinical study was to determine whether significant dimension differences could be found between peri-implant soft tissue supported by an IR and that immediately after removal of the restoration and to assess the changes over time. MATERIAL AND METHODS: Optical scans were made of 12 single implant sites in the esthetic zone of 10 participants. The scans in the first group replicated the peri-implant soft tissue contour with the support of the IR; in the second group, scans were made at different times from 0 seconds to 20 minutes after removal of the restoration. The changes in the soft tissue contour, including the height of the mesial papilla, distal papilla, and gingival margin, the facial and palatal soft tissue thickness, and emergence profile discrepancies (EPDs), were assessed. A linear mixed model was built to estimate the EPD. RESULTS: After the removal of IR, the palatal soft tissue thickness increased over time, and only minimal changes were found in the height of the mesial papilla, distal papilla, and gingival margin (up to -0.27 mm at 20 minutes). A significant EPD was immediately present at all the measurement sites after the removal of the IR. The linear mixed model showed a significant positive correlation between the natural logarithm of time and EPD. Significant positive correlations between gingiva thickness/implant depth and EPD were only seen at some of the sites. CONCLUSIONS: A small reduction in the papilla level occurred, but no clinical influence on the proximal contact design of the restoration was detected. For the emergence profile, a significant but small discrepancy occurred immediately and continued to increase over time.

miR-320a regulates high mobility group box 1 expression and inhibits invasion and metastasis in hepatocellular carcinoma.

BACKGROUND & AIMS: Several studies have shown that miR-320a induces apoptosis, inhibits cell proliferation, and affects cell cycle progression as a tumour suppressor in many cancers. However, the involvement of miR-320a in the invasion and metastasis of hepatocellular carcinoma (HCC) is still unknown. METHODS: Endogenous miR-320a and high mobility group box 1 (HMGB1) expressions were assayed by real-time PCR. Luciferase activities were measured using a dual-luciferase reporter assay system. Western blots were used to determine the protein expressions of HMGB1, MMP2, and MMP9. Invasion and metastasis of tumour cells were, respectively, evaluated by the transwell invasion assay and the wound healing assay. RESULTS: The expression of miR-320a was significantly decreased in 24 of 32 (75%) HCC tissues and associated with the invasion and metastasis of HCC. Furthermore, we demonstrated that HMGB1 was a direct target of miR-320a and there was a significant negative correlation between miR-320a and HMGB1 expression in HCC. Ectopic expression or inhibition of miR-320a potently regulated the invasion and metastasis of HCC cells in HMGB1-dependent manner. CONCLUSIONS: Our results showed that miR-320a was involved in the invasion and metastasis by targeting HMGB1 and had an anti-metastasis effect in HCC.

2D-Mn2C12: An Optimal Electrocatalyst with Nonbonding Multiple Single Centers for CO2-to-CH4 Conversion.

The CO2 reduction reaction (CO2RR) is a promising method that can both mitigate the greenhouse effect and generate valuable chemicals. The 2D-M2C12 with high-density transition metal single atoms is a potential catalyst for various catalytic reactions. Using an effective strategy, we screened 1s-Mn2C12 as the most promising electrocatalyst for the CO2RR in the newly reported 2D-M2C12 family. A low applied potential of -0.17 V was reported for the CO2-to-CH4 conversion. The relative weak adsorption of H atom and H2O in the potential range of -0.2 to -0.8 V, ensures the preferential adsorption of CO2 and the following production of CH4. The different loading amounts of Mn atoms on γ-graphyne (GY) were also investigated. The Mn atoms prefer doping in the nonadjacent triangular pores instead of the adjacent ones due to the repulsive forces between d-orbitals when the Mn loading is less than 32.3 wt % (5Mn). As the Mn concentration further increases, adjacent Mn atoms begin to appear, and the Mn@GY becomes metallic or half-metallic. The presence of four adjacent Mn atoms increases the d-band center of Mn@GY, particularly the dz2 center involved in CO2 adsorption, thereby enhancing the adsorption capacity for CO2. These findings indicate that 1s-Mn2C12 with high Mn atomic loadings is an excellent CO2RR electrocatalyst, and it provides new insights for designing efficient CO2RR electrocatalyst.

CCR2+ monocytes replenish border-associated macrophages in the diseased mouse brain.

Border-associated macrophages (BAMs) are tissue-resident macrophages that reside at the border of the central nervous system (CNS). Since BAMs originate from yolk sac progenitors that do not persist after birth, the means by which this population of cells is maintained is not well understood. Using two-photon microscopy and multiple lineage-tracing strategies, we determine that CCR2+ monocytes are significant contributors to BAM populations following disruptions of CNS homeostasis in adult mice. After BAM depletion, while the residual BAMs possess partial self-repopulation capability, the CCR2+ monocytes are a critical source of the repopulated BAMs. In addition, we demonstrate the existence of CCR2+ monocyte-derived long-lived BAMs in a brain compression model and in a sepsis model after the initial disruption of homeostasis. Our study reveals that the short-lived CCR2+ monocytes transform into long-lived BAM-like cells at the CNS border and subsequently contribute to BAM populations.

Novel role for Ddx39 in differentiation and telomere length regulation of embryonic stem cells.

Erk signaling is indispensable for the self-renewal and differentiation of mouse embryonic stem cells (ESCs), as well as telomere homeostasis. But how Erk regulates these biological processes remains unclear. We identified 132 Erk2 interacting proteins by co-immunoprecipitation and mass spectrometric analysis, and focused on Ddx39 as a potential Erk2 substrate. We demonstrated that Erk2 phosphorylates Ddx39 on Y132 and Y138. Ddx39 knockout (KO) ESCs are defective in differentiation, due to reduced H3K27ac level upon differentiation. Phosphorylation of Ddx39 promotes the recruitment of Hat1 to acetylate H3K27 and activate differentiation genes. In addition, Ddx39 KO leads to telomere elongation in ESCs. Ddx39 is recruited to telomeres by the telomere-binding protein Trf1, consequently disrupting the DNA loop formed by Trf1 and suppressing the alternative lengthening of telomeres (ALT). Phosphorylation of Ddx39 weakens its interaction with Trf1, releasing it from telomeres. Thus, ALT activity is enhanced, and telomeres are elongated. Altogether, our studies reveal an essential role of Ddx39 in the differentiation and telomere homeostasis of ESCs.

A Novel Peptide COX52-69 Inhibits High Glucose-induced Insulin Secretion by Modulating BK Channel Activity.

BACKGROUND: Excessive insulin is the leading cause of metabolic syndromes besides hyperinsulinemia. Insulin-lowering therapeutic peptides have been poorly studied and warrant urgent attention. OBJECTIVE: The main purpose of this study, was to introduce a novel peptide COX52-69 that was initially isolated from the porcine small intestine and possessed the ability to inhibit insulin secretion under high-glucose conditions by modulating large conductance Ca2+-activated K+ channels (BK channels) activity. METHODS AND RESULTS: Enzyme-linked immunosorbent assay results indicate that COX52-69 supressed insulin release induced by high glucose levels in pancreatic islets and animal models. Furthermore, electrophysiological data demonstrated that COX52-69 can increase BK channel currents and hyperpolarize cell membranes. Thus, cell excitability decreased, corresponding to a reduction in insulin secretion. CONCLUSION: Our study provides a novel approach to modulate high glucose-stimulated insulin secretion in patients with hyperinsulinemia.

Bioactive diterpenoids and sesquiterpenoids with different skeletons from Salvia digitaloides Diels.

Salvia has been regarded as a beneficial healing herb in ancient Egypt, Rome and Greece, and is listed as an official medicine in the pharmacopoeias of many countries worldwide. Currently, Salvia is widely used to flavor and preserve food. Here, two undescribed norabietane-type diterpenoids, sadigitaloides A and B, two undescribed germacrane-type sesquiterpenoids, sadigitaloides C and D, five undescribed guaiane-type sesquiterpenoid lactones, sadigitaloides E-I, two undescribed noreudesmane-type sesquiterpenoids, sadigitaloides J and K, one known diterpenoid, three known sesquiterpenoids, and three other types of known compounds were isolated from the 95% ethanol extract of the whole plants of Salvia digitaloides. Their structures and absolute configurations were characterized using 1D and 2D NMR spectroscopic techniques, electronic circular dichroism (ECD) calculations, HRESIMS experiments, and single-crystal X-ray diffraction analysis. Some compounds were evaluated for their anti-inflammatory activities against lipopolysaccharide (LPS)-induced TNF-α production in rat macrophage NR8383 cells. Sadigitaloide A showed noticeable anti-inflammatory activity at a concentration of 100.0 µM. At a concentration of 60 µM, sadigitaloide B exhibited better protection of dopaminergic neurons than the positive control n-butylidenephthalide in the Caenorhabditis elegans model injured by 6-OHDA. The phytotoxic activities of some compounds were attributed to considerable inhibitory effects on the growth of the roots and hypocotyls of Raphanus sativus L seedlings, especially cis, trans-abscisic acid, whose inhibition rates were much higher than those of glyphosate at concentrations ranging from 50 to 400 ppm. These results indicated that abietane-type diterpenoids possessed excellent anti-inflammatory and neuroprotective activities and further suggested that the low-molecular-weight compounds exhibited outstanding phytotoxic activities.

Antimicrobial diterpenoids from the leaves and twigs of Croton kongensis Gagnepain.

Croton kongensis Gagnepain. belongs to the genus Croton, the Euphorbiaceae family, mainly distributed in Hainan and southern Yunnan, China. The aim of present study was to acquire secondary metabolites of the ethanol extract obtained from the leaves and twigs of C. kongensis. Three new abietane-type diterpenoids, crokongenolides A-C (1-3), together with seven known diterpenoids (4-10), were isolated from the leaves and twigs of C. kongensis. The structures of the new compounds were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS), and their absolute configurations were confirmed by single-crystal X-ray diffraction analysis or electronic circular dichroism (ECD) calculations. The absolute configuration of 4 was determined for the first time by single-crystal X-ray diffraction analysis with Cu-Kα irradiation. Some compounds were evaluated for their antimicrobial properties by assessing their inhibitory effects on Staphylococcus aureus, Candida albicans, and Escherichia coli. Compound 10 showed significant antimicrobial activity against S. aureus with MIC value of 1.56 µg/ml.

SPP1 promotes radiation resistance through JAK2/STAT3 pathway in esophageal carcinoma.

BACKGROUND: Therapeutic resistance to radiotherapy is one of the major obstacles in clinical practice that significantly affect the therapeutic efficiency and prognosis of human esophageal carcinoma (ESCA). Thus, it is critical to understand the molecular mechanisms of radiation resistance in ESCA. Secreted phosphoprotein 1 (SPP1) plays an essential role in various human cancers, but its role in radiation resistance remains unclear. METHOD: Cell culture and transfection; Cell Counting Kit-8 (CCK-8) assays; EdU incorporation assays; Patient sample collection and medical records review; Transwell assays; Colony formation assays; Wound healing assays; Western blot; Immunofluorescence; Immunohistochemistry; Irradiation; Flow cytometry; Animal studies; Human Apoptosis Array Kit; Bioinformatics. RESULT: In the current study, we reported the novel phenomenon that radiation-treated human ESCA cells upregulated SPP1 expression, which in turn contributed to the ESCA resistance to radiotherapy. We also reported the tumor-promoting effect of SPP1 in ESCA systematically and comprehensively. Furthermore, subsequent studies by knocking down or overexpressing SPP1 in human ESCA cells showed that SPP1 could facilitate the repair of DNA damage and the survival of tumor cells post-radiation in ESCA, which might contribute to the development of radiation resistance during the radiotherapy process. More detailed investigations on the downstream molecular pathway suggested that radiation could increase the phosphorylation level of JAK2 and STAT3 by increasing SPP1 expression. Further in vivo validation using a mouse ESCA xenograft model showed that SPP1 overexpression significantly increased tumor volume while either SPP1 knockdown or pharmacological inhibition of the JAK2-STAT3 pathway reduced tumor volume in a synergistic manner with radiotherapy. CONCLUSION: Collectively, these findings suggested that the SPP1/JAK2/STAT3 axis is a critical player in ESCA progression and radiation resistance, which is a potential therapeutic target for combined therapy with the standard radiotherapy regimen to improve curative effect and increase patients' survival with ESCA.

CD155 promotes radioresistance and malignancy of esophageal cancer by regulating Hippo-YAP pathway.

The expression of CD155 has been observed to increase in various human cancers, but its role in the development of esophageal cancer (EC) is unclear. Radiotherapy is one of the primary therapeutic options for EC. However, radioresistance is still a severe issue in EC treatment. In this study, Oncomine database mining, immunohistochemistry, and survival analysis showed that higher expression of CD155 in patients with EC than in healthy controls. In vitro and in vivo, we found for the first time that irradiation increased the expression of CD155 in EC cells. CD155 knockdown inhibited cell proliferation and migration and tumor formation, and significantly increased radiosensitivity in EC. The in vivo model with high CD155 expression significantly promoted the proliferation and migration of EC cells. Furthermore, increased CD155 expression was associated with poor prognosis in patients with EC. CD155 regulated the Hippo-Yap pathway, influencing cell proliferation and migration. Therefore, CD155 is essential for the proliferation, migration, and radioresistance of EC. CD155 inhibition may be a viable strategy for improving radiation treatment efficacy in individuals with EC.

Diterpenoids with α-glucosidase inhibitory activities from the fruits of Vitex trifolia Linn.

Viticis Fructus, known as "Man-jing-zi", are the fruits of the traditional Chinese medicine Vitex trifolia Linn. and its variant Vitex trifolia Linn. var. simplicifolia. These fruits are used as folk medicines to treat various diseases. Although V. trifolia is useful for treating diabetes, the antidiabetic effect of its purified constituents is still under investigation. The phytochemical investigation on the ethanol extract of the fruits of V. trifolia yielded four new labdane diterpenoids vitetrolins A-D (1-4), together with seven (5-11) known analogs. The structures of these compounds were elucidated by spectroscopy techniques and the absolute configuration of 4 was determined by electronic circular dichroism (ECD) calculations. The isolated diterpenoids were evaluated for their α-glucosidase inhibitory activities. Compounds 5, 6, 8, and 9 exhibited moderate inhibitory activities against α-glucosidase with IC50 values ranging from 44.9 ± 6.1 to 70.5 ± 5.5 µM.

A new diterpenoid from the leaves and twigs of Croton lachnocarpus Benth.

A new clerodane diterpenoid, crotolanin A (1), along with three known clerodane diterpenoids, crotoeurin B (2), teucvidin (3) and teucvin (4), was isolated from the ethanol extract of the leaves and twigs of Croton lachnocarpus Benth. Their structures were identified by extensive NMR spectroscopic and HRESIMS analyses. The dopaminergic neuroprotective activity of compounds 1-4 was tested by using transgenic Caenorhabditis elegans pathological model. Compound 2 alleviated dopaminergic neuron degeneration of worms induced by 6-hydroxydopamine (6-OHDA) that represented a potential therapy for Parkinson's disease (PD).

Diterpenoids and C13 Nor-Isoprenoid Identified From the Leaves and Twigs of Croton yanhuii Activating Apoptosis and Pyroptosis.

Croton yanhuii (Family Euphorbiaceae) is an annual aromatic plant endemic to Yunnan Province, China, which yields an aromatic, spicy oil used as a flavoring and fragrance. The aim of the present study was to acquire secondary metabolites from the leaves and twigs of C. yanhuii and to evaluate their cytotoxic activity. Five new diterpenoids, croyanhuins A-E (1-5), and one new C13 nor-isoprenoid, croyanhuin F (6), were isolated from the leaves and twigs of C. yanhuii. Their structures and absolute configurations were determined by extensive spectroscopic methods (1D and 2D NMR, IR, and HRESIMS) and confirmed by electronic circular dichroism (ECD) spectra or single-crystal X-ray diffraction analysis. Among the new terpenoids, compounds 1 and 3 inhibited cell proliferation and viability in a dose- and time-dependent manner, whereas both induced cleavage of either caspase-3 or PARP-1 in the SW480 cell line. Additionally, we observed that Z-YVAD-FMK and Z-VAD-FMK, two caspase inhibitors, inhibited the compound-dependent cell viability loss, suggesting that either of them can induce pyroptosis and caspase-dependent apoptosis. These biological assay results revealed that compounds 1 and 3 induce different kinds of programmed cell death in SW480 cells.

Caesalpinbondin A, a Novel Diterpenoid Lactone With an Unprecedented Carbon Skeleton from the Seeds of Caesalpinia bonduc.

One novel diterpenoid lactone named caesalpinbondin A (1) that possesses an unprecedented tetracyclic ring system in which a 6/6/5-fused tricyclic ring and a 4,5-dimethyldihydrofuran-2(3H)-one were connected by a C-C single bond comprising a 5-(naphtho [2,3-b]furan-7-yl)dihydrofuran-2(3H)-one moiety was isolated from the seeds of Caesalpinia bonduc. Its chemical structure was established by extensive spectroscopic methods, and its absolute configuration was further determined by single-crystal X-ray diffraction analysis and electronic circular dichroism calculation. The biological evaluation suggested that compound 1 demonstrated potent anti-Alzheimer's disease (AD) bioactivity, which could delay paralysis of transgenic AD Caenorhabditis elegans. A possible biogenetic pathway of 1 was also proposed.

The oxidative products of methionine as site and content biomarkers for peptide oxidation.

Biomarkers for peptide/protein oxidation under oxidative stress (OS) hold both incredible application potential as well as significant challenges. In this article, liquid chromatography and mass spectrometry were applied to establish a new method for evaluating the oxidation site and degree of peptide oxidized, with its oxidative product serving as biomarker. In the three model peptides, peptide FMRF (containing a methionine) was prone to undergo oxygen addition under UV/H(2)O(2) oxidization, forming a sulfoxide (FM(O)RF) with a stable chromatographic peak separate from the model peptides. The oxidation content of FMRF, expressed as S(FM(O)RF)/(S(FM(O)RF) + S(FMRF)), is positively correlated with oxidation time. Based on sequence analysis of FM(O)RF, the oxidation mechanism (site and extent) of FMRF under UV/H(2)O(2) oxidization was explicitly clarified. By comparing the specific injury to each model peptide, we found that the oxidative products of Met-containing peptides are good biomarkers for OS. This research not only expands the range of biomarkers for OS, but also provides an efficient and accurate method for evaluating oxidation damage to peptides and even proteins.