RESUMEN
Type 2 diabetic osteoporosis (T2DOP) has received increasing attention from researchers. In this study, a total of 453 publications related to T2DOP from 2013 to 2022 were analyzed using bibliometric and visual analysis to identify the research trends and research hotspots in the field of T2DOP. PURPOSE: The objective of this study was to conduct a comprehensive bibliometric analysis of T2DOP-related publications from 2013 to 2022 to determine global research trends in T2DOP in terms of number of publications, countries/regions, institutions, authors, journals, funding agencies, and keywords. METHODS: All data were collected from the Web of Science Core Collection (WoSCC). All original research publications regarding T2DOP from 2013 to 2022 were retrieved. VOSviewer and Microsoft Office Excel were used to conduct the bibliometric and visual analysis. RESULTS: From 2013 to 2022, 515 relevant publications were published, with a peak in 2022 in the annual number of publications. The countries leading the research were USA and China. Sugimoto was the most influential authors. Capital Medical University and Nanjing Medical University were the most prolific institutions. Osteoporosis International was the most productive journal concerning T2DOP research. National Natural Science Foundation of China was the primary funding source for this research area. "Bone-mineral density", "fracture risk", and "postmenopausal women" were the most high-frequency keywords over the past 10 years. CONCLUSION: This was the first bibliometric study of diabetes mellitus and osteoporosis to exclusively examine type 2 diabetes mellitus. Our findings would provide guidance to understand the research frontiers and hot directions in the near future.
Asunto(s)
Bibliometría , Diabetes Mellitus Tipo 2 , Osteoporosis , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Osteoporosis/epidemiología , Investigación Biomédica/estadística & datos numéricosRESUMEN
As the demand for sustainable energy has increased, photoautotrophic cyanobacteria have become a popular platform for developing tools in synthetic biology. Although genetic tools are generally available for several model cyanobacteria, such tools have not yet been developed for many other strains potentially suitable for industrial applications. Additionally, most inducible promoters in cyanobacteria are controlled by chemical compounds, but adding chemicals into growth media on an industrial scale is neither cost-effective nor environmentally friendly. Although using light-controlled promoters is an alternative approach, only a cyanobacterial expression system inducible by green light has so far been described and employed for such applications. In this study, we have established a conjugation-based technique to express a reporter gene (eyfp) in the nonmodel cyanobacterium, Chlorogloeopsis fritschii PCC 9212. We also identified a promoter specifically activated by far-red light from the Far-Red Light Photoacclimation gene cluster of Leptolyngbya sp. JSC-1. This promoter, PchlFJSC1, was successfully used to drive eyfp expression. PchlFJSC1 is tightly regulated by light quality (i.e., wavelength) and leads to an approximately 30-fold increase in EYFP production when cells were exposed to far-red light. The induction level was controlled by the far-red light intensity, and induction stopped when cells were returned to visible light. This system has the potential for further applications in cyanobacteria by providing an additional choice of light wavelength to control gene expression. Collectively, this study developed a functional gene-expression system for C. fritschii PCC 9212 that can be regulated by exposing cells to far-red light.
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Cianobacterias , Cianobacterias/genética , Cianobacterias/metabolismo , Luz , Regiones Promotoras Genéticas/genéticaRESUMEN
Ultraviolet radiation (UVB) can result in photodamage to the skin and can seriously threaten health, particularly in the elderly. Oxidative stress and the inflammatory response have been shown to play a significant role in the process. In a previous study, we isolated, purified and identified a polysaccharide from the extract of Dendrobium huoshanense (DHPW1). In this study we evaluated the effect of DHPW1 on ameliorating the UVB photodamage of human immortalized keratinocytes (HaCaT). Cell proliferation and cell scratch assays were used to evaluate the viability of the HaCaT treated with DHPW1, and a fluorescent probe and Western blot analysis were used to examine the production of reactive oxygen species (ROS) and the expression of proinflammatory factors IL-1ß, IL-6, and NF-κB(p65). The results show that, compared with the control group (UVB irradiation only), DHPW1 significantly improved the viability of UVB-irradiated HaCaT and enhanced the migration rate of the cell scratch after 24 h. The scratch-healing rate reached 90 % after 36 h. DHPW1 also significantly inhibited UVB-induced oxidative stress and expression of proinflammatory factors . Compared with the control group, the production of ROS decreased by 49.11 %, and the relative protein expression of IL-6 and NF-κB(p65) decreased by up to 13.30 % and 31.02 %, respectively. It is concluded that DHPW1 can significantly improve viability and wound closure rate of UVB-irradiated HaCaT. In addition, it can reduce the expression of IL-1 and IL-6 by inhibiting the transcription of NF-κB(p65), thereby reducing inflammation and oxidative stress in UVB-irradiated HaCaT.
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FN-kappa B , Rayos Ultravioleta , Anciano , Línea Celular , Humanos , Interleucina-6/metabolismo , Queratinocitos , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Rayos Ultravioleta/efectos adversosRESUMEN
An Escherichia coli ATP-dependent two-component protease, ClpYQ(HslUV), targets the SulA molecule, an SOS induced protein. ClpY recognizes, unfolds and translocates the substrates into the proteolytic site of ClpQ for degradation. ClpY is divided into three domains N, I and C. The N domain is an ATPase; the C domain allows for oligomerization, while the I domain coordinates substrate binding. In the ClpYQ complex, two layer pore sites, pore I and II, are in the center of its hexameric rings. However, the actual roles of two outer-loop (130~159 aa, L1 and 175~209 aa, L2) of the ClpY-I domain for the degradation of SulA are unclear. In this study, with ATP, the MBP-SulA molecule was bound to ClpY oligomer(s). ClpYΔL1 (ClpY deleted of loop 1) oligomers revealed an excessive SulA-binding activity. With ClpQ, it showed increased proteolytic activity for SulA degradation. Yet, ClpYΔL2 formed fewer oligomers that retained less proteolytic activity, but still had increased SulA-binding activity. In contrast, ClpYΔpore I had a lower SulA-binding activity. ClpYΔ pore I ΔL2 showed the lowest SulA-binding activity. In addition, ClpY (Q198L, Q200L), with a double point mutation in loop 2, formed stable oligomers. It also had a subtle increase in SulA-binding activity, but displayed less proteolytic activity. As a result, loop 2 has an effect on ClpY oligomerization, substrate binding and delivery. Loop 1 has a role as a gate, to prevent excessive substrate binding. Thus, accordingly, ClpY permits the formation of SulA-ClpY(6x), with ATP(s), and this complex then docks through ClpQ(6x) for ultimate proteolytic degradation.
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Endopeptidasa Clp/genética , Endopeptidasa Clp/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteolisis , Secuencia de Aminoácidos/genética , Sitios de Unión , Escherichia coli/enzimología , Escherichia coli/genética , Mutagénesis Sitio-Dirigida , Unión Proteica , Dominios Proteicos/genética , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
Methionine is critical for variety of metabolic processes in biological organisms, acting as a precursor or intermediate for many final products. The last step for the synthesis of methionine is the methylation of homocysteine, which is catalyzed by MetE. Here, we use Salmonella enterica serovar Typhimurium LT2 to study the regulation of the metE+ gene by an anaerobically induced small non-coding RNA-FnrS, the expression of which is strictly dependent on the anaerobic regulator-FNR. The MetE-HA protein was expressed at an increased level in the fnrS- and hfq- deficient strains under anaerobic conditions. The Hfq protein is predicted to stabilize the binding between small RNA(s) and their target mRNA(s). A transcriptional (op) and translational (pr) metE::lacZ fusion gene were separately constructed, with the metE+-promoter fused to a lacZ reporter gene. In an anaerobic environment, the metE::lacZ (pr) fusion gene and reverse transcription-PCR identified that FnrS and/or FNR negatively regulate metE+ mRNA levels in the rich media. Analysis of FnrS revealed a sequence complementary to the 5' mRNA translational initiation region (TIR) of the metE+ gene. Mutation(s) predicted to disrupt base pairing between FnrS and metE+ TIR were constructed in fnrS, and most of those resulted in the loss of repressive activity. When compensatory mutation(s) were made in metE+ 5' TIR to restore base pairing with FnrS, the repressive regulation was completely restored. Therefore, in this study, we identified that in anaerobic phase, there is a repression of metE+ gene expression by FnrS and that base-paring, between both expressive transcripts, plays an important role for this negative regulation.
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Proteínas Bacterianas/genética , Regulación Bacteriana de la Expresión Génica , Metiltransferasas/genética , ARN Bacteriano/genética , ARN Mensajero/genética , ARN Pequeño no Traducido/genética , Salmonella typhimurium/enzimología , Proteínas Bacterianas/metabolismo , Emparejamiento Base , Secuencia de Bases , Regulación Enzimológica de la Expresión Génica , Metiltransferasas/química , Metiltransferasas/metabolismo , Conformación de Ácido Nucleico , ARN Bacteriano/química , ARN Bacteriano/metabolismo , ARN Mensajero/química , ARN Mensajero/metabolismo , ARN Pequeño no Traducido/química , ARN Pequeño no Traducido/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismoRESUMEN
In Escherichia coli, ClpYQ (HslUV) is a two-component ATP-dependent protease, in which ClpQ is the peptidase subunit and ClpY is the ATPase and unfoldase. ClpY functions to recognize protein substrates, and denature and translocate the unfolded polypeptides into the proteolytic site of ClpQ for degradation. However, it is not clear how the natural substrates are recognized by the ClpYQ protease and the mechanism by which the substrates are selected, unfolded and translocated by ClpY into the interior site of ClpQ hexamers. Both Lon and ClpYQ proteases can degrade SulA, a cell division inhibitor, in bacterial cells. In this study, using yeast two-hybrid and in vivo degradation analyses, we first demonstrated that the C-terminal internal hydrophobic region (139thâ¼149th aa) of SulA is necessary for binding and degradation by ClpYQ. A conserved region, GFIMRP, between 142th and 147th residues of SulA, were identified among various Gram-negative bacteria. By using MBP-SulA(F143Y) (phenylalanine substituted with tyrosine) as a substrate, our results showed that this conserved residue of SulA is necessary for recognition and degradation by ClpYQ. Supporting these data, MBP-SulA(F143Y), MBP-SulA(F143N) (phenylalanine substituted with asparagine) led to a longer half-life with ClpYQ protease in vivo. In contrast, MBP-SulA(F143D) and MBP-SulA(F143S) both have shorter half-lives. Therefore, in the E. coli ClpYQ protease complex, ClpY recognizes the C-terminal region of SulA, and F143 of SulA plays an important role for the recognition and degradation by ClpYQ protease.
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Proteasas ATP-Dependientes/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Adenosina Trifosfatasas/metabolismo , Proteínas Bacterianas/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Modelos Moleculares , Mutación Puntual , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Análisis de Secuencia de Proteína , Eliminación de Secuencia , Técnicas del Sistema de Dos HíbridosRESUMEN
Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years. More and more emerging evidences have demonstrated that they play important regulatory roles in various biological activities and disease progression including drug resistance. In the present study, a MTX-resistant colorectal cell line HT-29 (HT-29-R) was developed, which displayed the active proliferation and shortened cell cycle. LncRNA H19 was found to be significantly upregulated in this resistant cell line. Further investigation showed that H19 knockdown sensitized the MTX resistance in HT-29-R cells while its overexpression improved the MTX resistance in the parental cells, suggesting that H19 mediate MTX resistance. The Wnt/ß-catenin signaling was activated in HT-29-R cells, and H19 knockdown suppressed this signaling in the parental cells. In conclusion, H19 mediated MTX resistance via activating Wnt/ß-catenin signaling, which help to develop H19 as a promising therapeutic target for MTX resistant CRC.
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Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/genética , ARN Largo no Codificante/genética , Vía de Señalización Wnt , Neoplasias Colorrectales/genética , Células HT29 , Humanos , Metotrexato/farmacologíaRESUMEN
Four new rotenoid glycosides, namely amorphaside A-D (1-4), along with four known ones (5-8) were isolated from the seeds of Amorpha fruticosa. Their chemical structures and absolute configurations were elucidated by HRESIMS, NMR and CD spectra, as well as deduction from biosynthesis route. The sugar units were determined by acid hydrolysis, appropriate derivatization and HPLC analysis. The in vitro anti-proliferative activities of all compounds were evaluated against MCF-7 and HCT-116 cell lines. The results showed that compounds 1-3 had no effect on cell proliferation in the two cell lines even with the concentration of 50 µM, and compounds 4, 7 and 8 had selective cytotoxicity against MCF-7 with IC50 values of 3.90, 0.95 and 34.08 µM, respectively, while compounds 5 and 6 both showed significant cytotoxicity to the two cell lines with IC50 values less than 2.00 µM, even better than the positive control cisplatin. These preliminary results indicated that compounds 5 and 6 might be valuable to anticancer drug candidates.
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Antineoplásicos Fitogénicos/farmacología , Fabaceae/química , Flavonoides/farmacología , Glicósidos/farmacología , Semillas/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/química , Flavonoides/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Células HCT116 , Humanos , Células MCF-7 , Estructura MolecularRESUMEN
OBJECTIVE: To examine the apoptotic effect of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from Pteris semipinnata L (PsL), in human lung cancer A549 cells. METHODS: A549 cells were treated with 5F (0-80 µg/ml) for different time periods. Cytotoxicity was examined using a MTT method. Cell cycle was examined using propidium iodide staining. Apoptosis was examined using Hoechst 33258 staining, enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis. Expression of representative apoptosis-related proteins was evaluated by Western blot analysis. Reactive oxygen species (ROS) level was measured using standard protocols. Potential interaction of 5F with cisplatin was also examined. RESULTS: 5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. 5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase. Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis. The expression of p21 was increased. 5F exposure also increased Bax expression, release of cytochrome c and apoptosis inducing factor (AIF), and activation of caspase-3. 5F significantly sensitized the cells to cisplatin toxicity. Interestingly, treatment with 5F did not increase ROS, but reduced ROS production induced by cisplatin. CONCLUSION: 5F could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis.
RESUMEN
OBJECTIVE: To investigate the effect of Pteris semipinnata L. (PsL) extract Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F)-on HepG2 cells and explore its potential mechanism. METHODS: Cytotoxicity of 5F was studied in HepG2 cells treated with different doses of 5F (0 - 80 mg/L) for 24 h and cell viability was determined by MTT assay. To analyze apoptosis qualitatively, the Hoechst/PI assay was used. The level of Bax in mitochondria fraction of 5F-treated HepG2 cells was determined by western blotting. The levels of cyto-c and AIF in the cytosol were analyzed by western blotting. RESULTS: The cytotoxicity of 5F on HepG2 cells was elevated with the increasing of 5F concentrations, as evidenced by the cell viability assay. The apoptotic cells characterized by condensed neclei were observed after the exposure of HepG2 cells to 5F. The level of Bax in mitochondria fraction of 5F-treated HepG2 cells increased. The levels of cyto-c and AIF in the cytosol of 5F-treated HepG2 cells increased. CONCLUSION: 5F mediated apoptosis involves mitochondria-dependent pathway and 5F might have a therapeutic value against human cancer cell lines and especially on hepatocellular carcinoma (HCC) cells.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Diterpenos/farmacología , Neoplasias Hepáticas/patología , Mitocondrias/metabolismo , Pteris/química , Antineoplásicos Fitogénicos/química , Factor Inductor de la Apoptosis/metabolismo , Western Blotting , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Células Hep G2 , Humanos , Estructura Molecular , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To establish the quality standard of PsL injections containing mainly 5F (ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid). METHOD: The identification of PsL was performed by thin-layer chromatography, and the content was determined by HPLC. The column was Hypersil C18 (4.6 mm x 250 mm, 5 microm), the mobile phase was the mixture of methane-water-acitic acid (55:45: 0.045) with a flow rate of 1.0 mL x min(-1), the detective wavelength was 254 nm, and the column temperature was maintained at 35 degrees C. The pH value and K+ content of the three batchs injection were determined with pH meter and flame photometric meter, and the contents of tannin, protein, oxalic acid salt and heavy metals were detected by deferent methods. RESULT: The TLC method was suitable for the identification of PsL5F. The linearity for 5F was obtained over the range of 30-240 microg x mL(-1) (r = 0.999 8), the average recovery of 5F was 99.8%. The injections were of pH value range from 7.80 to 8.20, K+ contents less than 10 mmol x L(-1), and the contents of tannin, protein, oxalic acid salt and heavy metals were qualified with the Chinese pharmacopoeia, respectively. CONCLUSION: It's sensitive and reliable that can be used as quality control methods of PsL5F injections.
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Diterpenos/química , Medicamentos Herbarios Chinos/química , Inyecciones , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To investigate the possible mechanisms of nobiletin for anticancer by studying the inhibition effects of nobiletin on tubulin polymerization. METHOD: In vitro nobiletin was added into the tubulin polymerization-depolymerization system and the absorption values were recorded at 350 nm under 37 degrees C. RESULT: As compared with controls, the absorption values in reaction system decreased significantly in nobiletin treatment groups. When nobiletin final concentrations in reaction system were 5.0, 7.5, 10.0 and 12.5 micromol x L(-1), the maximum absorption values were 0 130, 0.109, 0.086 and 0.071 with 16.7%, 30.1%, 44.9% and 54.5% of inhibition rate, respectively. The results suggested that nobiletin could inhibit tubulin polymerization. CONCLUSION: The inhibition effect of nobiletin on tubulin polymerization is the possible mechanism for anticancer.
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Flavonas/farmacología , Moduladores de Tubulina/farmacología , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Animales , Unión Proteica/efectos de los fármacos , PorcinosRESUMEN
OBJECTIVE: To observe the effect of Armillaria mellea polysaccharide on mice bone marrow cells damage caused by Cyclophosphamide. METHOD: Kunming purebred mice were used and stochastic divided into 5 groups: normal control group, positive control group (rhG-CSF 20 microg x kg(-1) x d(-1)), damage group of Cyclophosphamide (150 mg x kg(-1) x d(-1)), the protective group with A. mellea polysaccharide, low dose (25.0 mg x kg(-1) x d(-1)) and high dose (50.0 mg x kg(-1) x d(-1)). Positive control was s.c. rhGCSF 6 d and i.p. Cyclophosphamide 3 d. A. mellea polysaccharide was i.p. 8 d. and Cyclophosphamide i.p. 3 d. WBC, RBC, PLT, BMNC were counted in peripheral blood and bone marrow cells. The myelogram were analyzed in bone marrow. RESULT: The WBC, RBC, PLT, BMNC of protective group and positive control group were higher than damage group (P < 0.01) significantly high dose group increaser than low dose group in protective group the numbed of Promyelocytic and lobulation nuclear of marrow. CONCLUSION: A. mellea polysaccharide has preferably protective effect on damaging mice bone marrow cell caused by Cyclophosphamide.