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Ribosomal proteins (RPs) play an important role in the overall stability, function, and integrity of ribosomes. Ribosomal protein L4 (RPL4), which is encoded by RPL4, is assumed to play different roles in different cancers due to the strong correlation between them. However, research based on the underlying mechanisms of this correlations is limited. Therefore, this study investigated the biological role of RPL4 in various cancers. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to compare the differential expression of RPL4 in tumor and normal tissues. The Sangerbox database and Kaplan-Meier method were employed to assess RPL4's impact on the prognosis of pan-cancer. Analyses using the cBioPortal tool, Shiny Methylation Analysis Resource Tool (SMART), and MethSurv provided insights into the methylation and epigenetic alterations of RPL4. Gene enrichment analysis revealed that RPL4 is involved in ribosome biogenesis through multiple pathways, and its enrichment in signaling pathways directly or indirectly influence tumor development. Tumor Immune Single-cell Hub (TISCH) was used to analyze RPL4 expression levels and cellular functions in the tumor microenvironment. Tumor Immune Estimation Resource Database 2.0 (TIMER2.0) and Tumor-Immune System Interactions Database (TISIDB) tools revealed that RPL4 affected the immune infiltration potential of tumors. Furthermore, the application of the ROC mapper and CellMiner databases indicated an association between RPL4 and sensitivity to multiple antitumor drugs. Additionally, RPL4 was found to remodel the tumor immune microenvironment, leading to the development of chemoresistance. In conclusion, the findings suggest that RPL4 can be used as a potential tumor biomarker and may serve as a target for immunotherapy in various cancers. Genetic testing of RPL4 provides a foundation for the diagnosis, prognosis, and treatment of clinical tumors.
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Antibiotic pollution in the environment has a negative impact on ecosystem security. Taking the Oujiang River Basin as an example,high-performance liquid chromatography mass spectrometry(LC-MS)was used to detect the concentration of six classes of 35 antibiotics in the surface water of the southern Zhejiang River Basin. The concentration level and spatial distribution of antibiotics were analyzed,the risk of antibiotics to ecology and human health were assessed using relevant models,and the sources of antibiotics were discussed. The results showed that in 20 sampling sites,a total of four classes of 12 antibiotics were detected,including sulfonamides,quinolones,tetracyclines,and lincosamides. The total concentration was ND-1 018 ng·L-1. The highest detection rate was that of Lincomycin(90.48%),followed by that of sulfapyridine(38.10%). The three antibiotics with the highest average concentrations were ofloxacin(12.49 ng·L-1),Lincomycin(11.08 ng·L-1),and difloxacin(7.38 ng·L-1). Antibiotics in the basin showed mainly spotty pollution,which had large spatial differentiation. The average concentration of antibiotics in the upstream(54.39 ng·L-1)was higher than that mid-downstream(46.64 ng·L-1). The degree of antibiotic pollution from upstream to downstream showed a characteristic of being "sparse in the upstream and dense in the downstream. " This indicated that the concentration of antibiotics in the upstream was significantly different,whereas the pollution degree of antibiotics in the downstream was uniform. The upstream was mainly polluted by health,livestock,and poultry breeding wastewater emissions,and downstream pollution was mainly caused by densely populated activities and the rapid development of economy,trade,and industry. The ecological risk assessment results showed that the upstream site H6 had the highest risk quotient,ofloxacin and enrofloxacin had high risk levels, and lincomycin had a moderate risk level. Health risk assessment results showed that the Oujiang River surface water antibiotics posed no risk to human health.
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Antibacterianos , Contaminantes Químicos del Agua , Humanos , Antibacterianos/análisis , Ecosistema , Monitoreo del Ambiente/métodos , Ofloxacino/análisis , Lincomicina , Medición de Riesgo , Agua/análisis , China , Contaminantes Químicos del Agua/análisisRESUMEN
A series of 1-(2-oxocyclohexyl)butane-1, 3-dione derivatives were designed and synthesized as TLR4 inhibitors by modifying the core structure of the lead compound ((6, 8-dioxo-1, 2, 3, 4, 6, 7, 8, 8a-octahydronaphthalen-2-yl) carbamate)). In vitro, compound 3p significantly inhibited the proliferation of rat synovial cells, inhibited the proliferation of LPS-induced RAW264.7 cells, and inhibited TLR4 activity, with IC50 values of 1.21 ± 0.09 µM, 0.73 ± 0.05 µM and 0.43 ± 0.03 µM, respectively, which was superior to the positive control methotrexate. In vivo anti-rheumatoid arthritis evaluation, compound 3p can significantly inhibit the inflammatory factors TNF-α, IL-1ß and IL-6, so as to achieve the therapeutic purpose. In the preliminary mechanism study, compound 3p has obvious regulatory effects on the abnormal increase of TLR4, JAK2 and STAT3 protein and gene expression related to inflammatory signaling pathway in RAW264.7 cells. In summary, this study aims to develop more effective candidates for rheumatoid arthritis.
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Artritis Reumatoide , Sinoviocitos , Ratas , Animales , Receptor Toll-Like 4/genética , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Sinoviocitos/metabolismo , Lipopolisacáridos/farmacología , FN-kappa B/metabolismoRESUMEN
The natural products have a new chemical structure and biological active diversity, so they are favored by scientific researchers. Gout is a high incidence and high-risk disease, and the current treatments are not satisfactory. Xanthine oxidase (XO) is a key enzyme responsible for the development and progression of various metabolic and oxidative stress-related diseases. Excessive activity of XO leads to elevated serum urate levels, which in turn leads to the development of hyperuricemia. This review mainly introduces the recent progress of the new research on the anti-gout activity of natural products that could provide new treatment methods for gout and information for the discovery and development of new anti-gout drugs.
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Productos Biológicos , Gota , Hiperuricemia , Humanos , Xantina Oxidasa , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Gota/tratamiento farmacológico , Hiperuricemia/tratamiento farmacológico , Inhibidores Enzimáticos/químicaRESUMEN
Rheumatoid arthritis (RA) is a chronic and systemic disease of inflammatory synovitis with unknown etiology. In previous studies, we found that the double-ring conjugated enone structure has anti-rheumatoid arthritis activity and could effectively inhibit the proliferation of rat synovial cells in vitro and has good anti-inflammatory activity in vivo. Herein, we further modified the structure, which was a novel double-ring conjugated enone, to study its anti-rheumatoid arthritis activity. Results showed that the most potent compound 32 could effectively inhibit the proliferation of rat synovial cells in vitro and has better anti-inflammatory activity compared with that of the positive control methotrexate, as shown by in vivo activity evaluation. More interestingly, compound 32 could effectively inhibit the increase of TNF-α, IL-1ß, and IL-6 induced by LPS and regulate the expression of TLR4, MyD88, NF-κB, and IκB in the signaling pathway of TLR4/NF-κB. Our results provided a promising starting point for the development of highly effective small molecules for the treatment of RA.
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In order to explore the potential anti-tumor activity functional molecules, a series of Fissitungfine B derivatives were designed and synthesized. Their anti-tumor activity effects on Hela, MCF-7 and A-549 cell lines were evaluated in vitro. The results showed that some of these Fissitungfine B derivatives exhibited moderate to good anti-tumor activities. Especially, compound 4 g with the highest inhibitory activities against all tested cell lines with the Hela was IC50 = 3.82 ± 0.56 µM, MCF-7 was IC50 = 5.53 ± 0.68 µM, and A-549 was IC50 = 4.55 ± 0.53 µM. Furthermore, the compounds 4 g have higher inhibitory effects on TDP2 in vitro. In vivo, the biological activities assay results showed that the target compound 4 g had a good inhibitory effect on tumor growth. The target compound 4 g could inhibit tumor growth well, which might be use as a candidate drug or lead compound for further research and development anti-tumor agents.
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Antineoplásicos , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Proteínas de Unión al ADN/farmacología , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Estructura Molecular , Hidrolasas Diéster Fosfóricas , Relación Estructura-ActividadRESUMEN
Background: Acute sleep loss increases the brain's reactivity toward positive and negative affective stimuli. Thus, despite well-known reduced attention due to acute sleep loss, we hypothesized that humans would gaze longer on happy, angry, and fearful faces than neutral faces when sleep-deprived. We also examined if facial expressions are differently perceived after acute sleep loss. Methods: In the present, within-subjects study, 45 young adults participated in one night of total sleep deprivation and one night with an 8-hour sleep opportunity. On the morning after each night, an eye tracker was used to measure participants' time spent fixating images of happy, angry, fearful, and neutral faces. Participants also evaluated faces' attractiveness, trustworthiness, and healthiness on a 100-mm visual analog scale. Results: Following sleep loss, participants struggled more fixating the faces than after sleep. The decrease in total fixation duration ranged from 6.3% to 10.6% after sleep loss (P<0.001). Contrary to our hypothesis, the reduction in total fixation duration occurred irrespective of the displayed emotion (P=0.235 for sleep*emotion interaction) and was also present for the upper (P<0.001) but not the lower part of the faces (except for the lower part of angry faces). Overall, faces were evaluated as less trustworthy (-2.6 mm) and attractive (-3.6 mm) after sleep loss (p<0.05). Discussion: Facial expressions are crucial for social interactions. Thus, spending less time fixating on faces after acute sleep loss may come along with several problems for social interactions, eg, inaccurate and delayed judgment of the emotional state of others. In addition, more negative social impressions of others may lead to social withdrawal in sleep-deprived humans.
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The preparation of purified polysaccharides was described from fresh onions by hot water extraction, protein removal and dialysis treatment. The structure of onion polysaccharide was confirmed by 13C NMR, DEPT, COSY, HSQC and HMBC. In order to study the structure-activity relationship of onion polysaccharide, the derivatives of onion polysaccharide including acetylated onion polysaccharide and phosphoric onion polysaccharide were prepared. On this basis, the antioxidant activities of onion polysaccharide and its derivatives were tested in vitro. The results showed that onion polysaccharides and its derivatives had a good antioxidant activity, and the activity of phosphorylated polysaccharide was similar to that of Vc positive control.
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Antioxidantes , Cebollas , Antioxidantes/química , Carbohidratos de la Dieta , Depuradores de Radicales Libres/química , Polisacáridos/química , Diálisis RenalRESUMEN
The polysaccharide from Morinda citrifolia fermentation liquor was extracted by the hot water method. The acetylated polysaccharide, phosphorylated polysaccharide, carboxymethylated polysaccharide, and sulfated polysaccharide were identified by IR and NMR spectra. The results showed that Morinda citrifolia polysaccharide and its derivatives showed the good antioxidant activity, and them up to Vc level. These results provide a good basis for studying the antioxidant activity and structural-activity relationship of Morinda citrifolia polysaccharide and its derivatives.
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Morinda , Antioxidantes/química , Antioxidantes/farmacología , Morinda/química , Extractos Vegetales/química , Polisacáridos/química , Polisacáridos/farmacología , Sulfatos/químicaRESUMEN
Rheumatoid arthritis (RA) is a chronic disease that seriously affects human health and quality of life, and it is one of the main causes of labor loss and disability. Many countries have listed rheumatoid arthritis as one of the national a key diseases to tackle. The pathogenesis of RA in humans is still unknown, and medical researchers believe that the pathogenesis of RA may be the result of a combination of genetic and environmental factors. RA is an incurable condition that can only be controlled and treated with conventional drugs. In this paper, the pathologic features and pathogenesis of RA were introduced, and the research progress of new anti-rheumatoid arthritis chemical drugs in recent years was reviewed.
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Artritis Reumatoide , Calidad de Vida , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/etiología , HumanosRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disease with unknown etiology and pathogenesis, in which butyrylcholinesterase (BuChE) plays an important role in the pathogenesis and progression. Inhibition of BuChE is a potential strategy for the treatment of advanced AD. Herein, the advantages and disadvantages of various synthesis methods on BuChE inhibitors and their inhibitory activities were summarized.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Acetilcolinesterasa , Enfermedad de Alzheimer/tratamiento farmacológico , Butirilcolinesterasa , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , HumanosRESUMEN
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
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Butirilcolinesterasa/farmacología , Inhibidores de la Colinesterasa/farmacología , Acridinas/química , Acridinas/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Butirilcolinesterasa/efectos adversos , Butirilcolinesterasa/química , Inhibidores de la Colinesterasa/efectos adversos , Inhibidores de la Colinesterasa/química , Humanos , Metoxaleno/análogos & derivados , Metoxaleno/química , Metoxaleno/farmacología , Relación Estructura-ActividadRESUMEN
Polysaccharides have anti-virus, anti-cancer, anti-oxidation, immune regulation, hypoglycemia and other biological activities. Because of their safety, fewer side effects and other advantages, polysaccharides are considered as ideal raw materials in food and drugs. The biological activity of polysaccharides can be improved by structural modification (such as sulfation, carboxymethylation, phosphorylation, etc.), and even new biological activity can be generated. In this review, the recent advances in the phosphorylation of polysaccharides were reviewed from the perspectives of modification methods, structures, biological activities and structure-activity relationships.
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Ésteres/síntesis química , Ésteres/farmacología , Polisacáridos/síntesis química , Polisacáridos/farmacología , Animales , Ésteres/toxicidad , Humanos , Estructura Molecular , Fosforilación , Polisacáridos/toxicidad , Relación Estructura-ActividadRESUMEN
Cholinesterase (ChE) inhibitors can be divided into two categories: acetylcholinesterase (AChE) inhibitors and butylcholinesterase (BuChE) inhibitors. Therefore, the development of selective inhibition of AChE and BuChE activities is the central content of ChE pharmacochemistry research. In order to clarify the progress of AChE inhibitor-based design, synthesis, and activity studies, we reviewed the pharmacochemical and pharmacological properties of selective AChE inhibitors over the past decade. We hope that this review will make it easier for readers to understand the development of new drug chemistry methods for AChE inhibitors in order to develop more effective and selective AChE inhibitors.
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Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/farmacología , Aminoquinolinas/química , Animales , Antraquinonas/química , Humanos , Salicilamidas/química , Estilbenos/químicaRESUMEN
The relationship between TLR4 and inflammation-related diseases has been paid more and more attention. The studies have shown that TLR4/NF-κB signaling pathway plays an important role in the transmission of inflammatory signals. A large number of pro-inflammatory factors, chemokines, adhesion factors, TLR4 and its ligands interact with each other, and jointly promote the development of diseases. In this work, 8 target compounds were synthesized to screen the inhibitory activity of TLR4 in vitro. The results of TLR4 inhibition test in vitro showed that the double-ring conjugated enones had a good inhibitory activity, and the IC50 value of compound 4f was 0.56 ± 0.10 µM, and it was superior to the positive control methotrexate. To further study the anti-inflammatory effect and mechanism of double-ring conjugated enones by using LPS induced rat synovial cell inflammation model. The results of the mechanism test showed that compound 4f could effectively promote the apoptosis of rat synovial cells, and the mechanism might be related to the up-regulation of the expression of apoptosis-related protein Caspase-3. In addition, compound 4f could significantly inhibit the increase of inflammatory factors TNF-α, IL-1ß and IL-6 in rat synovial cells induced by LPS, showing a good anti-inflammatory activity. In the TLR4/NF-κB signaling pathway test of rat synovial cells, compound 4f can effectively regulate the expression levels of TLR4, MyD88, NF-κB and IκB related proteins in TLR4/NF-κB signaling pathway, which may be due to its inhibition of LPS-induced inflammation in rat synovial cells. At the same time, it inhibits the abnormal proliferation of cells and its important mechanism promoted of apoptosis.
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Antiinflamatorios/farmacología , Antirreumáticos/farmacología , Ciclohexanonas/farmacología , Receptor Toll-Like 4/antagonistas & inhibidores , Animales , Antiinflamatorios/síntesis química , Antirreumáticos/síntesis química , Apoptosis/efectos de los fármacos , Artritis Reumatoide/tratamiento farmacológico , Cicloheptanos/síntesis química , Cicloheptanos/farmacología , Ciclohexanonas/síntesis química , Ratas , Transducción de Señal/efectos de los fármacos , Líquido Sinovial/citologíaRESUMEN
The activities of marine alkaloids are manifested in antifungus and antimalaria. The optimization process, chemical synthesis, antimalarial activity, and antibacterial activity of various compounds were discussed.
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Alcaloides/química , Antibacterianos/síntesis química , Antimaláricos/síntesis química , Alcaloides/síntesis química , Alcaloides/farmacología , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antimaláricos/química , Antimaláricos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Poríferos/química , Poríferos/metabolismo , Relación Estructura-ActividadRESUMEN
The polysaccharide of yam was extracted by hot water method and purified by column chromatography. The physicochemical properties of Chinese yam polysaccharide were analyzed by UV, IR, GPC, 1D-NMR and 2D-NMR spectra. The results showed that Chinese yam polysaccharide had α-d-Gluc-(1 â 4) glycoside bond, and the C2 hydroxyl group was replaced by ethoxyl group. The average molecular weight was determined to be 7.28 × 104. It showed that The scavenging effect of yam polysaccharide on hydroxyl radicals was similar to VC. The sulfated polysaccharide (SP), phosphorylated polysaccharide (PP), carboxymethylated polysaccharide (CP) and acetylated polysaccharide (A-P) were identified by IR and NMR. The results showed that P and its derivatives showed good antioxidant activity. Especially, their scavenging ability to hydroxyl radicals reached the level of VC. This laid a theoretical foundation for the development of yam polysaccharide-related foods.
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Antioxidantes/química , Dioscorea/química , Polisacáridos/química , Depuradores de Radicales Libres/química , Radical Hidroxilo/química , Metilación , Peso Molecular , Sulfatos/químicaRESUMEN
Marine alkaloids were divided into five categories from the perspective of anti-tumor activity. The optimization process, chemical synthesis, anti-tumor activity evaluation and structure-activity relationship of various compounds were discussed.
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Alcaloides/farmacología , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Alcaloides/química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Neoplasias/patologíaRESUMEN
Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 µM respectively. At the same time, the LDH release and LD50 test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.
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Annonaceae/química , Antirreumáticos/síntesis química , Antirreumáticos/farmacología , Diseño de Fármacos , Animales , Antirreumáticos/efectos adversos , Antirreumáticos/química , L-Lactato Deshidrogenasa/metabolismo , Modelos Moleculares , Estructura Molecular , Ratas , Relación Estructura-Actividad , Membrana Sinovial/citologíaRESUMEN
[This retracts the article DOI: 10.1039/D0RA05856D.].