RESUMEN

Enterocytozoon bieneusi and Encephalitozoon spp. are microsporidian pathogens with zoonotic potential that pose significant public health concerns. To ascertain the occurrence and genotypes of E. bieneusi and Encephalitozoon spp., we used nested PCR to amplify the internal transcribed spacer (ITS) gene and DNA sequencing to analyze 198 fecal samples from red pandas from 6 zoos in China. The total rate of microsporidial infection was 15.7% (31/198), with 12.1% (24/198), 1.0% (2/198), 2.0% (4/198) and 1.0% (2/198) for infection rate of E. bieneusi, Encephalitozoon cuniculi, Encephalitozoon intestinalis and Encephalitozoon hellem, respectively. One red panda was detected positive for a mixed infection (E. bieneusi and E. intestinalis). Red pandas living in semi-free conditions are more likely to be infected with microsporidia (χ2 = 6.212, df = 1, p < 0.05). Three known (SC02, D, and PL2) and one novel (SCR1) genotypes of E. bieneusi were found. Three genotypes of E. bieneusi (SC02, D, SCR1) were grouped into group 1 with public health importance, while genotype PL2 formed a separate clade associated with group 2. These findings suggest that red pandas may serve as a host reservoir for zoonotic microsporidia, potentially allowing transmission from red pandas to humans and other animals.

RESUMEN

Molecular interactions in energetic materials form the key not only to the "structure stability, energy storage, ignition, and detonation" dynamics but also to the sensitivity to the loading of perturbation and the power intensity of radiation for the energetic substance, with the nature of the interactions remaining elusive. With the aid of perturbative Raman spectroscopy and the pressure-resolved density functional theory, we uncovered that the H-N bond of the intermolecular O:H-N bonds for LLM-105 shares the same negative compressibility and thermal expansivity of the H-O bond for the coupling O:H-O bond of water [Phys. Rep. 2023, 998, 1-68]. In contrast, the dangling H-N bond vibrating at a 3440 cm-1 high frequency does otherwise due to the absence of coupling interaction and the undercoordination-driven bond contraction. These findings should deepen our insight into interactions involving electron lone pairs and offer an efficient means for discriminating the performance of individual bonds.

RESUMEN

GV-971 (sodium oligomannate) is a China Food and Drug Administration (CFDA)-approved drug for treating Alzheimer's disease, and it could inhibit Aß fibril formation in vitro and in mouse studies. To elucidate the mechanisms for understanding how GV-971 modulates Aß's aggregation, we conducted a systematic biochemical and biophysical study of Aß40/Aß42:GV-971 systems. The integrating analysis of previously published data and our results suggests that the multisite electrostatic interactions between GV-971's carboxylic groups and Aß40/Aß42's three histidine residues might play a dominant role in driving the binding of GV-971 to Aß. The fuzzy-type electrostatic interactions between GV-971 and Aß are expected to protect Aß from aggregation potentially through breaking the histidine-mediated inter-Aß electrostatic interactions. Meanwhile, since GV-971's binding exhibited a slight downregulation effect on the flexibility of Aß's histidine-colonized fragment, which potentially favors Aß aggregation, we conclude that the dynamics alteration plays a minor role in GV-971's modulation on Aß aggregation.

Asunto(s)

Enfermedad de Alzheimer , Péptidos beta-Amiloides , Ratones , Animales , Péptidos beta-Amiloides/química , Histidina , Enfermedad de Alzheimer/metabolismo , Fragmentos de Péptidos/química

RESUMEN

Femtosecond time-resolved coherent anti-Stokes Raman spectroscopy (CARS) was used to study the dynamics of the vibrational modes of liquid chloroform. The vibrational modes were selectively excited and their coherent vibrational dynamics were obtained. Some subtle features that are difficult to distinguish in the ordinary spontaneous Raman spectrum, such as overtones and combinations of some fundamental vibrational modes, were recognized from the CARS transients. Combined with theoretical calculations, the contributions of chlorine isotopes were also confirmed from the CARS transients of the vibrational modes involving the motion of chlorine atoms.

RESUMEN

Purpose: Mitochondrial dysfunction refers to cancer immune evasion. A novel 7-gene prognostic signature related to the mitochondrial DNA copy number was utilized to evaluate the immunocyte infiltration in colon cancer according to the risk scores and to predict the survival for colon cancer. Experimental design: We performed an integrated bioinformatic analysis to analyze transcriptome profiling of the EB-treated mitochondrial DNA-defected NCM460 cell line with differentially expressed genes between tumor and normal tissues of COAD in TCGA. The LASSO analysis was utilized to establish a prognostic signature. ESTIMATE and CIBERSORT validated the differences of immunocyte infiltration between colon cancer patients with high- and low-risk scores. Results: Our study identified a 7-gene prognostic signature (LRRN2, ANKLE1, GPRASP1, PRAME, TCF7L1, RAB6B, and CALB2). Patients with colon cancer were split into the high- and low-risk group by the risk scores in TCGA (training cohort: HR = 2.50 p < 0.0001) and GSE39582 (validation cohort: HR = 1.43 p < 0.05). ESTIMATE and CIBERSORT revealed diverseness of immune infiltration in the two groups, especially downregulated T-cell infiltration in the patients with high-risk scores. Finally, we validated the colon patients with a low expression of the mitochondrial number biomarker TFAM had less CD3+ and CD8+ T-cell infiltration in clinical specimens. Conclusion: An mtDNA copy number-related 7-gene prognostic signature was investigated and evaluated, which may help to predict the prognosis of colon cancer patients and to guide clinical immunotherapy via immunocyte infiltration evaluation.

RESUMEN

Introduction: Aberrations in cell cycle control is defined as one of the hallmarks of cancer, while cyclin D1 is an essential protein to cell cycle which promote G1 phase into S phase, and frequently overexpressed in many human cancers. However, new functions have been identified in transgenic mice models, including the transcription of genome, the development of chromosome instability and DNA repair. In this research, our aim is to find the function of cyclin D1 in transcription in human cancers. Methods: The correlation of the cyclin D1 expression levels and prognosis of cervical cancer patients were analyzed in tissue microarray (TMA) cohort. We chose C33A as our main research object. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq), to find out the genes differentially expressed in C33A, cyclin D1 knock-in C33A and cyclin D1 knock-down C33A. Results: We found that upregulation of cyclin D1 was associated with shorter overall survival (OS) and disease-free survival (DFS). Functionally, we identified 422 genes differentially expressed through analysis of the results of ChIP-seq and RNA-seq. These genes are highly enriched in Gene Ontology categories and involve in diverse cellular functions via KEGG classification, including replication and repair, signal transduction, cell growth and death. Conclusion: These findings suggested that the expression of cyclin D1 was associated with the prognosis of patients with cervical cancer. Cyclin D1 can serve both to activate and downregulate gene expression as a transcriptional role directly binding with genome DNA, which means that cyclin D1 may be a key protein during oncogenesis and tumor development.

RESUMEN

BACKGROUND: Mitochondrial ribosomal protein L15 (MRPL15), a member of mitochondrial ribosomal proteins whose abnormal expression is related to tumorigenesis. However, the prognostic value and regulatory mechanisms of MRPL15 in non-small-cell lung cancer (NSCLC) remain unclear. METHODS: GEPIA, ONCOMINE, Gene Expression Omnibus (GEO), UALCAN, Kaplan-Meier plotter, PrognoScan, LinkedOmics and GeneMANIA database were utilized to explore the expression and prognostic value of MRPL15 in NSCLC. Additionally, immune infiltration patterns were evaluated via ESTIMATE algorithm and TISIDB database. Furthermore, the expression and prognostic value of MRPL15 in lung cancer were validated via immunohistochemistry (IHC) assays. RESULTS: In NSCLC, multiple cohorts including GEPIA, ONCOMINE and 8 GEO series (GSE8569, GSE101929, GSE33532, GSE27262, GSE21933, GSE19804, GSE19188, GSE18842) described that MRPL15 was up-regulated. Moreover, MRPL15 was notably linked to gender, clinical stage, lymph node status and the TP53 mutation status. And patients with high MRPL15 expression showed poor overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and relapse-free survival (RFS) in NSCLC. Then, functional network analysis suggested that MRPL15 participated in metabolism-related pathways, DNA replication and cell cycle signaling via pathways involving several kinases, miRNAs and transcription factors. Additionally, it was found that MRPL15 expression was negatively related to immune infiltration, including immune scores, stromal scores and several tumor-infiltrating lymphocytes (TILs). Furthermore, IHC results further confirmed the high MRPL15 expression and its prognostic potential in lung cancer. CONCLUSIONS: These findings demonstrate that high MRPL15 expression indicates poor prognosis in NSCLC and reveal potential regulatory networks as well as the negative relationship with immune infiltration. Thus, MRPL15 may be an attractive predictor and therapeutic strategy for NSCLC.

RESUMEN

Triple-negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis and the highest metastatic and recurrence potential, which represents 15-20% of all breast cancers in Chinese females, and the 5-year overall survival rate is about 80% in Chinese women. Recently, emerging evidence suggested that aberrant alternative splicing (AS) plays a crucial role in tumorigenesis and progression. AS is generally controlled by AS-associated RNA binding proteins (RBPs). Monocyte chemotactic protein induced protein 1 (MCPIP1), a zinc finger RBP, functions as a tumor suppressor in many cancers. Here, we showed that MCPIP1 was downregulated in 80 TNBC tissues and five TNBC cell lines compared to adjacent paracancerous tissues and one human immortalized breast epithelial cell line, while its high expression levels were associated with increased overall survival in TNBC patients. We demonstrated that MCPIP1 overexpression dramatically suppressed cell cycle progression and proliferation of TNBC cells in vitro and repressed tumor growth in vivo. Mechanistically, MCPIP1 was first demonstrated to act as a splicing factor to regulate AS in TNBC cells. Furthermore, we demonstrated that MCPIP1 modulated NFIC AS to promote CTF5 synthesis, which acted as a negative regulator in TNBC cells. Subsequently, we showed that CTF5 participated in MCPIP1-mediated antiproliferative effect by transcriptionally repressing cyclin D1 expression, as well as downregulating its downstream signaling targets p-Rb and E2F1. Conclusively, our findings provided novel insights into the anti-oncogenic mechanism of MCPIP1, suggesting that MCPIP1 could serve as an alternative treatment target in TNBC.

Asunto(s)

Empalme Alternativo/genética , Proliferación Celular/fisiología , Ciclina D1/metabolismo , Factores de Transcripción NFI/metabolismo , Ribonucleasas/metabolismo , Factores de Transcripción/metabolismo , Mama/metabolismo , Carcinogénesis/genética , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica/genética , Genes Supresores de Tumor/fisiología , Humanos , Recurrencia Local de Neoplasia/genética , Neoplasias de la Mama Triple Negativas/patología

RESUMEN

Melanoma is a life-threatening form of skin cancer with an elevated risk of metastasis and high mortality rates. The prognosis and clinical outcomes of cancer immunotherapy in melanoma patients are influenced by immune cell infiltration in the tumor microenvironment (TME) and the expression of genetic factors. Despite reports suggesting that immune-classification may have a better prediction of prognosis compared to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM-classification, the definition of Immunoscore in melanoma is becoming a difficult challenge. In this study, we established and verified a 7-gene prognostic signature. Melanoma patients from the Cancer Genome Atlas (TCGA) were separated into a low-risk group and a high-risk group using the median risk score. Receiver operating characteristic (ROC) analysis for overall survival (OS) showed that the area under the curve (AUC) was 0.701 for 1 year, 0.726 for 3 years, and 0.745 for 5 years, respectively. Moreover, a nomogram was constructed as a practical prognostic tool, and the AUC was 0.829 for 3 years, and 0.803 for 5 years, respectively. Furthermore, we validated the above results in two datasets from the Gene Expression Omnibus (GEO) database and the relationship between 7-gene prognostic signature and immune infiltration estimated.

Asunto(s)

Linfocitos Infiltrantes de Tumor/metabolismo , Melanoma/genética , Neoplasias Cutáneas/genética , Bases de Datos Genéticas , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Humanos , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/inmunología , Melanoma/mortalidad , Pronóstico , Supervivencia sin Progresión , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo

RESUMEN

Radiation resistance affects survival in non-small-cell lung cancer (NSCLC) patients. Further exploration of mechanisms and targets is urgently needed. Using bioinformatic analyses, we found that UBE2T is associated with survival, tumor size, lymph node metastasis and distant metastasis. Then, real-time PCR and immunohistochemistry were performed to explore the differentially expressed genes between normal and NSCLC tissues. Furthermore, we used colony formation, EdU incorporation, scratch, transwell assays, flow cytometry, immunofluorescence and western blot to assess the role of UBE2T in vitro and in vivo. RNA-Seq and coimmunoprecipitation were used to explore the mechanism. The results showed that UBE2T promotes proliferation, migration, invasion, and radiation resistance in vitro and in vivo by accelerating the G2/M transition and inhibiting apoptosis. Mechanistically, UBE2T promotes epithelial-mesenchymal transition (EMT) via ubiquitination-mediated FOXO1 degradation and Wnt/ß-catenin signaling pathway activation. Moreover, FOXO1 reversed radiation resistance and EMT. Therefore, UBE2T may be a potential target for enhancing radiotherapy sensitivity and serve as a biomarker to predict prognosis.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas/patología , Proteína Forkhead Box O1/metabolismo , Neoplasias Pulmonares/patología , Tolerancia a Radiación , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Ratones , Metástasis de la Neoplasia , Trasplante de Neoplasias , Pronóstico , Proteolisis , Carga Tumoral , Ubiquitinación , Vía de Señalización Wnt

RESUMEN

Triple-negative breast cancer (TNBC) stands for a refractory subtype, which predicts poor prognosis and has no effective therapies yet for improving it. Given the restrictions of traditional treatments, novel therapeutic strategies need excavating to alleviate the intrinsic or acquired resistance. Ribociclib, a selective CDK4/6 inhibitor, has successfully prevented cancers from deteriorating by intervening the CDK4/6-cyclin D-Rb-E2F pathway, especially for estrogen receptor-positive (ER +) breast cancer. However, there still remains limited accessibility referring to TNBC. Performing experiments on MDA-MB-231 cells, we found that LEE011 could suppress cell proliferation, and this suppression tended to be dose-dependently. Western blotting analysis presented significant decrease with the expression of CDK4/6 after LEE011 treated, and other proteins associated with this axis such as cyclin D1, p-Rb, Rb, E2F1 showed aberrant changes. Moreover, LEE011 induced G0-G1 phase cell cycle arrest, promoted cell apoptosis, and reduced cell migration in vitro. In addition, tumor growth was remarkably impeded without obvious side-effects in MDA-MB-231 xenograft models. Our research has identified that LEE011 was not completely invalid for MDA-MB-231. Considering its pivotal status in TNBC, the CDK4/6-cyclin D-Rb-E2F pathway informed us the possibility and practicality of Ribociclib (LEE011) as pharmacological intervention, but challenges warrant further validation in prospective studies.

Asunto(s)

Aminopiridinas/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/farmacología , Purinas/farmacología , Aminopiridinas/uso terapéutico , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Ciclina D1/metabolismo , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/uso terapéutico , Factor de Transcripción E2F1/metabolismo , Femenino , Humanos , Masculino , Neoplasias Mamarias Experimentales , Ratones , Ratones Desnudos , Fosforilación/efectos de los fármacos , Purinas/uso terapéutico , Proteína de Retinoblastoma/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Carga Tumoral/efectos de los fármacos

RESUMEN

Cervical cancer remains one of the main factors leading to tumor-related death worldwide. Many strategies of cancer treatment such as chemotherapy are developed and used nowadays. However, for the cancer chemotherapy resistance, reduction of the limitation of cancer chemotherapy efficacy is one of the aims of several oncology teams. Moreover, the cyclin-dependent kinase 4/6-cyclin D-retinoblastoma protein-E2F pathway is an important mechanism for cell cycle control and its dysregulation is one of the key factors for cancers development including cervical cancer. Ribociclib is one of the selective CDK4/6 inhibitors and is a new therapeutic approach showing promise as a good strategy of therapy in many human cancers. However, there are not the studies regarding the investigation of effects of Ribociclib in cervical cancer yet. In the present study, by western blotting and immunofluorescence assay, we found respectively that CDK4, CDK6 and cyclin D1 are highly expressed and are mostly localized in the nucleus with some localized in the cytoplasm of cervical cancer cell lines. Moreover, Ribociclib induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited C33A cell proliferation in dose - dependent manner following by decreased expression of certain related genes such as CDK4, CDK6, E2F1, P-Rb, and increased Bax expression. In C33A xenografts, Ribociclib inhibited tumor growth associated with decreased expressions of CDK4, CDK6, cyclin D1, Rb and Ki-67, and also significantly increased tumor cell apoptosis. However, we didn't find side effect of Ribociclib concerning heart, liver and kidney perturbation and any Ribociclib anti-tumor effects on HeLa in vitro and in vivo which may be due to Hela cell infection by HPV. Based on our findings, the Rb-E2F pathway can be considered as an important factor in human cervical cancer pathogenesis and as a mechanism of Ribociclib, a potential strategy of treatment for the improvement of new therapeutic measures for the treatment of HPV-negative cervical cancer which application for HPV-positive cervical cancer is desired in further study.

Asunto(s)

Aminopiridinas/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Purinas/farmacología , Neoplasias del Cuello Uterino/enzimología , Aminopiridinas/uso terapéutico , Animales , Apoptosis/fisiología , Proliferación Celular/fisiología , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Células HeLa , Humanos , Masculino , Ratones , Ratones Desnudos , Purinas/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos

RESUMEN

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant carcinomas and its molecular mechanisms remain unclear. Long noncoding RNA (lncRNA) could bind sites of miRNA which affect the expression of mRNA according to the competing endogenous (ceRNA) theory. The aim of the present study was to construct a ceRNA network and to identify key lncRNA to predict survival prognosis. We identified differentially expressed mRNA, lncRNA and miRNA between tumor tissues and normal tissues from The Cancer Genome Atlas database. Then, using bioinformatics tools, we explored the connection of 89 lncRNA, 10 miRNA and 22 mRNA, and we constructed the ceRNA network. Furthermore, we analyzed the functions and pathways of 22 differentially expressed mRNA. Then, univariate and multivariate Cox regression analyses of these 89 lncRNA and overall survival were explored. Nine lncRNA were finally screened out in the training group. The patients were divided into high-risk and low-risk groups according to the 9 lncRNA and low-risk scores having better clinical overall survival (P < .01). Furthermore, the receiver operating characteristic curve demonstrates the predicted role of the 9 lncRNA. The 9-lncRNA signature was successfully proved in the testing group and the entire group. Finally, multivariate Cox regression analysis and stratification analysis further proved that the 9-lncRNA signature was an independent factor to predict survival. In summary, the present study provides a deeper understanding of the lncRNA-related ceRNA network in ccRCC and suggests that the 9-lncRNA signature could serve as an independent biomarker to predict survival in ccRCC patients.

Asunto(s)

Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , ARN Largo no Codificante/genética , Anciano , Carcinoma de Células Renales/mortalidad , Femenino , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , ARN Mensajero/genética , Curva ROC

RESUMEN

In this study, the TEMPO-mediated (TEMPO/NaBr/NaClO) oxidation pattern of curdlan was investigated through comprehensively structural analysis of the corresponding oxidized products. During the structural analysis, infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography tandem multiple angle laser scattering (GPC-MALS) and ultra-high performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) were applied. As a result, the homogenous ß1-3 polyglucuronic acids (MW, 49.8, 29.8 and 7.0 kDa) were obtained with proper amount of oxidant (5.36 mmol NaClO) at various temperatures (4, 25, 50 °C), respectively. Compared to the oxidation of 1-4 linked glucan (starch and cellulose) with TEMPO-mediated system at same reaction conditions, higher degree of specific oxidation and less degradation were observed in that of 1-3 linked curdlan. The glycosylation at position 3 could stabilize the sugar ring, which inactivates the non-specific oxidation related hydroxyl groups on the sugar ring. Thus, the TEMPO-mediated system has higher selectivity to oxidize the primary hydroxyl groups of 1-3 linked curdlan and form polyglucuronic acid than those observed in the oxidation of starch and cellulose. In addition, same as those observed in previous work about starch, higher the temperature was used in the oxidation with TEMPO system, higher the activity of oxidant (NaClO solution) was, more non-specific oxidation occurred, and more the degradation were observed.

RESUMEN

Heparin, a highly sulfated glycosaminoglycan, has been used as a clinical anticoagulant over 80 years. Low molecular weight heparins (LMWHs), heparins partially depolymerized using different processes, are widely used as clinical anticoagulants. Qualitative molecular weight (MW) and quantitative mass content analysis are two important factors that contribute to LMWH quality control. Size exclusion chromatography (SEC), relying on multiple angle laser scattering (MALS)/refractive index (RI) detectors, has been developed for accurate analysis of heparin MW in the absence of standards. However, the cations, which ion-pair with the anionic polysaccharide chains of heparin and LMWHs, had not been considered in previous reports. In this study, SEC with MALS/RI and inductively coupled plasma/mass spectrometry detectors were used in a comprehensive analytical approach taking both anionic polysaccharide and ion-paired cations heparin products. This approach was also applied to quantitative analysis of heparin and LMWHs. Full profiles of MWs and mass recoveries for three commercial heparin/LMWH products, heparin sodium, enoxaparin sodium and nadroparin calcium, were obtained and all showed higher MWs than previously reported. This important improvement more precisely characterized the MW properties of heparin/LMWHs and potentially many other anionic polysaccharides.

Asunto(s)

Química Farmacéutica/métodos , Cromatografía en Gel , Heparina de Bajo-Peso-Molecular/análisis , Heparina/análisis , Espectrometría de Masas , Refractometría , Anticoagulantes/química , Anticoagulantes/normas , Química Farmacéutica/normas , Enoxaparina/química , Heparina/química , Heparina de Bajo-Peso-Molecular/química , Peso Molecular , Análisis Espectral

RESUMEN

Selective excitation of C-H stretching vibrational modes, detection of intramolecular vibrational energy redistribution (IVR), and vibrational modes coupling in the electronic ground state of benzene are performed by using femtosecond time- and frequency-resolved coherent anti-Stokes Raman scattering (CARS) spectroscopy. Both of the parent modes in the Raman-active bands are coherently excited by an ultrafast stimulated Raman pump, giving initial excitations of 3056 cm-1 (A1g) and 3074 cm-1 (E2g) and subsequent IVR from the parent modes to daughter modes of 1181 and 992 cm-1, and the coherent vibrational coupling of the relevant modes is tracked. The directionality and selectivity of IVR and coherent coupling among all of the relevant vibrational modes are discussed in the view of molecular symmetry.

RESUMEN

The femtosecond time-resolved multiplex coherent anti-Stokes Raman scattering (CARS) technique has been performed to investigate intramolecular vibrational redistribution (IVR) through vibrational couplings in 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) molecules. In the multiplex CARS experiment, the supercontinuum (SC) was used as broad-band Stokes light to coherently and collectively excite multiple vibrational modes, and quantum beats arising from vibrational couplings among these modes were observed. The IVR of RDX is visualized by a topological graph of these vibrational couplings, and with analysis of the topological graph, two vibrational modes, both of which are assigned to ring bending, are confirmed to have coupling interactions with most of the other vibrational modes and are considered to have a tendency of energy transfer with these vibrational modes. We suggest that the mode at 466 cm-1 is a portal of energy transfer from outside to inside of the RDX molecule and the mode at 672 cm-1 is an important transit point of energy transfer in the IVR.

RESUMEN

A series of low-molecular-weight polymannuronate (LPM) and polyguluronate (LPG) polyanionic derivatives, including LPM/LPG phosphate (LPMP/LPGP), LPM/LPG H-phosphonate (LPMHP/LPGHP) and LPM/LPG sulfate (LPMS/LPGS), were prepared as heparinoids by chemical modification of LPM and LPG. The structures and characteristics of LPM, LPG and their derivatives were elucidated based on high performance gel permeation chromatography (HPGPC), fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and polyacrylamide gel electrophoresis (PAGE). In order to test the heparin-like activities of these derivatives and to reveal the activities affected by substituent groups and PM/PG polysaccharide backbones, the anticoagulant activities and FGF/FGFR1c signaling activation abilities were evaluated in vitro. The results showed that sulfate group was the best substituent group to improve the heparin-like activities of LPM/LPG compared with the other two anionic groups. The results also showed that sulfated derivative based on PG structure had better activities than that based on PM structure.