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Despite extensive studies on the thermodynamic mechanism governing molecular adsorption at the solid-water interface, a comprehensive understanding of the crucial role of interface properties in mediating the entropy-enthalpy compensation during adsorption is lacking, particularly at a quantitative level. Herein, we employed two types of surface models (hydroxyapatite and graphene) along with a series of amino acids to successfully elucidate how distinct interfacial features dictate the delicate balance between entropy and enthalpy variations. The adsorption of all amino acids on the hydroxyapatite surface is an enthalpy-dominated process, where the water-induced enthalpic component of the free energy and the surface-adsorbate electrostatic interaction term alternatively act as the driving force for adsorption in different regions of the surface. Although favorable interactions are observed between amino acids and the graphene surface, the entropy-enthalpy compensation exhibits dependence on the molecular size of the adsorbates. For small amino acids, favorable enthalpy changes predominantly determine their adsorption behavior; however, larger amino acids tend to bind more tightly with the graphene surface, which is thermodynamically dominated by the entropy variations despite the structural characteristics of amino acids. This study reveals specific entropy-enthalpy mechanisms underlying amino acid adsorption at the solid-liquid interface, providing guidance for surface design and synthesis of new biomolecules.
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OBJECTIVE: Imnovid® is an immunomodulatory drug with antineoplastic activity. The aim of this study was to evaluate the bioequivalence and safety of the generic drug pomalidomide (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and its originator product Imnovid® (Celgene Europe Ltd) in the fasting and fed states, respectively. METHODS: The research consisted of two parts: one with a dose of 1 mg and the other with a dose of 4 mg. 48 healthy subjects were included in each study and were divided into two groups (fasting group and fed group) at a 1:1 ratio to administrate study drugs orally. The plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The 90% CI of GMR for main pharmacokinetic (PK) parameters (Cmax, AUC0 - t and AUC0-∞) met the requirements of bioequivalence standards. The incidence and severity of AEs associated with pomalidomide and Imnovid® were similar. CONCLUSION: The results proved the PK parameters of pomalidomide and Imnovid® were similar and bioequivalent. Both drugs showed safety profile well.
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Talidomida , Equivalencia Terapéutica , Humanos , Área Bajo la Curva , Cápsulas , Cromatografía Liquida , Estudios Cruzados , Pueblos del Este de Asia , Ayuno , Voluntarios Sanos , Comprimidos , Espectrometría de Masas en Tándem , Talidomida/análogos & derivados , Talidomida/farmacocinéticaRESUMEN
The use of reclaimed water for nonpotable uses requires consideration of potential adverse health effects. Considering that inhalation can be a significant route of transmission of microorganisms and inflammatory agents, this study used a mouse model to test the possible adverse effects of reclaimed water use during car washing where aerosols are generated. Intensive innate immune responses were found in the lungs after acute exposure, and the lavage polymorphonuclear cell proportion was the most sensitive end point. Four types of evidence are presented to demonstrate that the main risk factor that initiates innate inflammation is the free endotoxin. (1) Small molecules (<10 kDa) cannot induce inflammation. (2) The endotoxin levels of 11 water samples from five different plants showed positive correlations with inflammatory responses. (3) Actual water samples showed similar activities with free endotoxins other than bacterially bound endotoxins. (4) Specific removal of endotoxins with polymyxin B affinity chromatography further confirmed the role of free endotoxins. It is noteworthy that 62.9% of the investigated tertiary-treated water had endotoxin levels higher than the allowable acute threshold (120 endotoxin units/mL) under the hypothesized car wash condition, which strongly suggests the need to carefully consider the water treatment steps required to produce safe water for various reclaimed water end uses.
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Endotoxinas , Exposición por Inhalación , Agua , Aerosoles , Animales , Masculino , Ratones , Factores de RiesgoRESUMEN
BACKGROUND: Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose-response relationship in the application of hydrogen is puzzling. We attempted to identify the dose-response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. METHODS: In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. RESULTS: Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. CONCLUSIONS: Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose-response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress.
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Agua Potable/administración & dosificación , Hidrógeno/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Gastropatías/tratamiento farmacológico , Estómago/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangre , Relación Dosis-Respuesta a Droga , Concentración de Iones de Hidrógeno , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Estómago/patología , Gastropatías/inducido químicamente , Gastropatías/metabolismo , Gastropatías/patologíaRESUMEN
Latuda® is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda®. After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda®. The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda® were as follows: the Cmax was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, Cmax, was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC0-t, AUC0-∞) were evaluated using average bioequivalence (ABE). The results indicate that both Cmax and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda® were as follows: the Cmax was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29).
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The microbiome is a predictor of clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Microbiota-derived metabolites can modulate these outcomes. How bacteria, fungi and viruses contribute to the production of intestinal metabolites is still unclear. We combined amplicon sequencing, viral metagenomics and targeted metabolomics from stool samples of patients receiving allo-SCT (n = 78) and uncovered a microbiome signature of Lachnospiraceae and Oscillospiraceae and their associated bacteriophages, correlating with the production of immunomodulatory metabolites (IMMs). Moreover, we established the IMM risk index (IMM-RI), which was associated with improved survival and reduced relapse. A high abundance of short-chain fatty acid-biosynthesis pathways, specifically butyric acid via butyryl-coenzyme A (CoA):acetate CoA-transferase (BCoAT, which catalyzes EC 2.8.3.8) was detected in IMM-RI low-risk patients, and virome genome assembly identified two bacteriophages encoding BCoAT as an auxiliary metabolic gene. In conclusion, our study identifies a microbiome signature associated with protective IMMs and provides a rationale for considering metabolite-producing consortia and metabolite formulations as microbiome-based therapies.
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Bacteriófagos , Trasplante de Células Madre Hematopoyéticas , Humanos , Bacteriófagos/genética , Heces/microbiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Bacterias/genética , Bacterias/metabolismo , Ácido Butírico/metabolismoRESUMEN
The development of robust nonplatinum electrocatalysts to enhance the performance of formate oxidation reaction (FOR) and oxygen reduction reaction (ORR) is one of the key issues for the commercialization of direct formate fuel cells (DFFCs), but still challenging. Herein, a structurally controlled 3D flower-like PdCu nanosheet (NS) catalyst is synthesized by a method of oil bath reduction under mild conditions as a bifunctional electrocatalyst for DFFCs. Under the dual tuning on the composition and intermetallic phase, the PdCu nanosheet catalyst exhibits 8.67 times higher mass activity for anodic formate oxidation reaction than the commercial Pd/C. For the cathodic ORR, a positive shift half-wave potential is obtained for PdCu nanosheets exceeding Pt/C. Moreover, after a long-term stability test, the current density of the PdCu nanosheet catalyst for FOR and ORR can be well maintained with the least activity decay. When the PdCu NSs are used as optimized anode and cathode electrodes for DFFCs enable a peak power density as high as 53 mW cm-2 at room temperature, which is about 1.3 times higher than that of the commercial Pd/C and Pt/C as anode and cathode electrodes. This work provides a potential strategy to improve the catalytic performance of non-Pt-based nanocatalysts.
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Bacteriophages play central roles in the maintenance and function of most ecosystems by regulating bacterial communities. Yet, our understanding of their diversity remains limited due to the lack of robust bioinformatics standards. Here we present ViroProfiler, an in-silico workflow for analyzing shotgun viral metagenomic data. ViroProfiler can be executed on a local Linux computer or cloud computing environments. It uses the containerization technique to ensure computational reproducibility and facilitate collaborative research. ViroProfiler is freely available at https://github.com/deng-lab/viroprofiler.
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Microbioma Gastrointestinal , Microbiota , Programas Informáticos , Reproducibilidad de los Resultados , Metagenoma , Metagenómica/métodos , Biología Computacional/métodos , Análisis de DatosRESUMEN
Hydrocarbon pollution poses substantial environmental risks to water and soil. Bioremediation, which utilizes microorganisms to manage pollutants, offers a cost-effective solution. However, the role of viruses, particularly bacteriophages (phages), in bioremediation remains unexplored. This study examines the diversity and activity of hydrocarbon-degradation genes encoded by environmental viruses, focusing on phages, within public databases. We identified 57 high-quality phage-encoded auxiliary metabolic genes (AMGs) related to hydrocarbon degradation, which we refer to as virus-encoded hydrocarbon degradation genes (vHYDEGs). These genes are encoded by taxonomically diverse aquatic phages and highlight the under-characterized global virosphere. Six protein families involved in the initial alkane hydroxylation steps were identified. Phylogenetic analyses revealed the diverse evolutionary trajectories of vHYDEGs across habitats, revealing previously unknown biodegraders linked evolutionarily with vHYDEGs. Our findings suggest phage AMGs may contribute to alkane and aromatic hydrocarbon degradation, participating in the initial, rate-limiting hydroxylation steps, thereby aiding hydrocarbon pollution bioremediation and promoting their propagation. To support future research, we developed vHyDeg, a database containing identified vHYDEGs with comprehensive annotations, facilitating the screening of hydrocarbon degradation AMGs and encouraging their bioremediation applications.
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Bacteriófagos , Hidrocarburos , Biodegradación Ambiental , Filogenia , Bacteriófagos/genética , AlcanosRESUMEN
BACKGROUND: Trastuzumab is a humanized anti-HER2 monoclonal antibody used in the treatment of breast cancer. This study compared the pharmacokinetics (PK), immunogenicity and safety of trastuzumab (Roche Pharma AG) and its biosimilar (Chia Tai Tianqing Pharmaceutical Group Co. Ltd) in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: A randomized, parallel, double-blind, single-dose study was conducted. Healthy male subjects were randomized to receive trastuzumab (n = 43) or its biosimilar (n = 43) intravenously at a dose of 4 mg. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and PK parameters were statistically analyzed. Safety and immunogenicity were also evaluated. RESULTS: The geometric mean ratios (GMRs) of AUC0-t, Cmax and AUC0-∞ for trastuzumab and its biosimilar were 92.3%, 100.77% and 92.2%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. No serious adverse events or immunogenicity were reported, and all the adverse events reported were mild and similar between the two treatment groups. CONCLUSIONS: Trastuzumab was well tolerated, showed a similar safety profile to its biosimilar, and demonstrated PK equivalence. CLINICAL TRIAL REGISTRATION: This trial was registered at the [anonymized].
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Biosimilares Farmacéuticos , Humanos , Masculino , Trastuzumab , Voluntarios Sanos , Método Simple Ciego , Área Bajo la Curva , Equivalencia Terapéutica , Método Doble CiegoRESUMEN
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. While a close correlation between chronic Helicobacter pylori infection and CRC has been reported, the role of the virome has been overlooked. Here, we infected Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive metagenomics analysis of H. pylori-induced changes in lower gastrointestinal tract bacterial and viral communities. We observed an expansion of temperate phages in H. pylori infected Apc+/1638N mice at the early stage of carcinogenesis. Some of the temperate phages were predicted to infect bacteria associated with CRC, including Enterococcus faecalis. We also observed a high prevalence of virulent genes, such as flgJ, cwlJ, and sleB, encoded by temperate phages. In addition, we identified phages associated with pre-onset and onset of H. pylori-promoted carcinogenesis. Through co-occurrence network analysis, we found strong associations between the viral and bacterial communities in infected mice before the onset of carcinogenesis. These findings suggest that the expansion of temperate phages, possibly caused by prophage induction triggered by H. pylori infection, may have contributed to the development of CRC in mice by interacting with the bacterial community.
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Bacteriófagos , Neoplasias Colorrectales , Microbioma Gastrointestinal , Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Bacteriófagos/genética , Viroma , Infecciones por Helicobacter/microbiología , Ratones Endogámicos C57BL , Neoplasias Colorrectales/microbiología , CarcinogénesisRESUMEN
Background: Ovarian cancer (OV) has been puzzling clinicians because of its poor prognosis. More and more evidence show that the G protein coupled receptor P2RY14 plays a key role in the initiation and progression of various types of human cancer. The purpose of our study is to explore the correlation between P2RY14 and the prognosis of ovarian cancer patients and the relevant mechanism. Methods: First, the differentially expressed gene P2RY14 was screened from The Cancer Genome Atlas (TCGA) database. Explored possible P2RY14 related miRNAs and lncRNAs through multiple public databases, predicted and analyzed the expression level of candidate miRNAs and candidate lncRNAs that can bind to candidate miRNAs in OV through StarBase database. The TIMER database was used to comprehensively analyze the expression of tumor infiltrating immune cells, and to analyze the correlation between the expression level of P2RY14 and the level of immune cell infiltration in OV or the expression level of immune checkpoints. Results: Patients with P2RY14 overexpression had better overall survival (OS) and progression-free interval (PFI). In the Targetscan database, 22 upstream miRNAs that may bind to P2RY14 were predicted. According to the regulatory network constructed by the Cytoscape software, correlation analysis and the role of miRNAs in the prognosis of OV, we first determined that the candidate miRNAs were miR-34c-5p. Then, we predicted the upstream lncRNAs of miR-34c-5p in the StarBase database, the expression level of these lncRNAs in OV in the Gene Expression Profiling Interactive Analysis (GEPIA) database, and the role in prognosis. We determined that LINC00665 is the most potential lncRNA upstream of ovarian cancer miRNA (hsa-miR-34c-5p)-P2RY14. Then, we analyzed the results in the Timer database, suggesting that P2RY14 expression was positively correlated with CD8+T Cell, CD4+T Cell, Macrophage, Neutral and Dendritic cells, and negatively correlated with B cells. Meanwhile, P2RY14 was positively correlated with CD274 and PDCD1. Conclusions: P2RY14 can be used as a new predictive biomarker of ovarian cancer. Intervention of P2RY14 can affect the prognosis of ovarian cancer by affecting LINC00665-miR-34c-5p-P2RY14 axis. These findings provide a potential target for the development of anti-cancer strategies for ovarian cancer.
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BACKGROUND: Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. RESEARCH DESIGN & METHODS: We designed a clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial. Each period, subjects were given 50 mg dasatinib or its generic. The RSABE (reference scale average bioequivalence) and ABE (average bioequivalence) methods were employed to assess bioequivalence by pharmacokinetics (PK) parameters for a highly variable drug. RESULTS: 32 and 24 eligible volunteers were enrolled in the fasting and postprandial trials, respectively. In the fasting trial, the RSABE method was performed, and point estimates of Cmax, AUC0-t, and AUC0-∞ met the bioequivalence criteria. In the postprandial trial, the ABE method was performed, and the 90% CI of the geometric mean ratio (GMR) for PK parameters met the requirements of bioequivalence standards. CONCLUSION: The results proved that the PK parameters of the two drugs were similar and bioequivalent, indicating that both drugs had a good safety profile. CLINICAL TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (Number: NCT05640804) and Drug Clinical Trial Registration and Information Disclosure Platform (Number: CTR20181708).
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Dasatinib , Medicamentos Genéricos , Pueblos del Este de Asia , Humanos , Área Bajo la Curva , Disponibilidad Biológica , Dasatinib/farmacocinética , Medicamentos Genéricos/farmacocinética , Ayuno , Equivalencia TerapéuticaRESUMEN
OBJECTIVE: Afatinib is an oral, irreversible ErbB family blocker. It binds covalently to the kinase domains of epidermal growth factor (EGFR), HER2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation. Our trial compared the bioequivalence and safety between afatinib produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Giotrif® produced by Boehringer Ingelheim. METHODS: Healthy Chinese subjects (N = 36) were randomly divided into two groups at a ratio of 1:1. There was a single dose per period of afatinib and Giotrif®. The washout was set as 14 days. Plasma drug concentrations of afatinib and Giotrif® were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. RESULTS: The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for afatinib and Giotrif® were 102.80%, 101.83%, and 101.58%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both drugs showed a good safety profile during the trial. CONCLUSION: This study showed that afatinib was bioequivalent to Giotrif® in healthy Chinese subjects with well safety. CHINESE CLINICAL TRIAL REGISTRY: This trial is registered at the Chinese Clinical Trial website ( http://www.chinadrugtrials.org.cn/index.html # CTR20171160).
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Afatinib , Pueblos del Este de Asia , Equivalencia Terapéutica , Humanos , Afatinib/efectos adversos , Afatinib/farmacología , Área Bajo la Curva , China , Cromatografía Liquida , Comprimidos , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. RESULTS: The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study. CONCLUSION: The study shows that the two drugs had similar bioequivalence and safety. CLINICAL TRIAL REGISTRATION: DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076.
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Pueblos del Este de Asia , Liraglutida , Humanos , Área Bajo la Curva , China , Cromatografía Liquida , Estudios Cruzados , Liraglutida/administración & dosificación , Liraglutida/efectos adversos , Liraglutida/sangre , Liraglutida/farmacocinética , Espectrometría de Masas en Tándem , Equivalencia Terapéutica , Inyecciones Subcutáneas , Monitoreo de DrogasRESUMEN
The human gut virome is comprised of diverse commensal and pathogenic viruses. The colonization by these viruses begins right after birth through vaginal delivery, then continues through breastfeeding, and broader environmental exposure. Their constant interaction with their bacterial hosts in the body shapes not only our microbiomes but us. In addition, these viruses interact with the immune cells, trigger a broad range of immune responses, and influence different metabolic pathways. Besides its key role in regulating the human gut homeostasis, the intestinal virome contributes to disease development in distant organs, both directly and indirectly. In this review, we will describe the changes in the gut virome through life, health, and disease, followed by discussing the interactions between the virome, the microbiome, and the human host as well as providing an overview of their contribution to gut disease and disease of distant organs.
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Bacteriófagos , Microbioma Gastrointestinal , Microbiota , Virus , Femenino , Humanos , Viroma , Tracto Gastrointestinal/microbiologíaRESUMEN
Background: This study sought to analyze long non-coding ribonucleic acid (lncRNA) LINC00273 expression in ovarian cancer tissues, and to preliminarily explore its effect on the growth and invasion of ovarian cancer cells and its influencing mechanism. Methods: Quantitative real-time polymerase chain reaction was performed to detect the LINC00273 expression levels of cancerous ovarian tissues and their related cell lines. The ovarian cancer cells with the highest expression of LINC00273 were transfected with a knockdown lentiviral vector targeting the LINC00273 sequence and a negative control plasmid. The effects of the LINC00273 knockdown on the invasion and growth of these cancerous cells were evaluated by clonogenic assays, flow cytometry, EdU (5-Ethynyl-2'-deoxyuridine), Cell Counting Kit-8, and Transwell assays. Western Blot was used to measure the LINC00273 knockdown effects on invasion and migration-related gene expression, and the knockdown effects on the ovarian proliferation ability of the cancer cells in vivo were analyzed by in vivo nude mouse experiments. Results: LINC00273 expression was significantly more increased in the cancerous ovarian tissues than the adjacent tissues. The LINC00273 expression of the ovarian cancer cell lines was higher than that of the normal ovarian epithelial cells. LINC00273 knockdown greatly suppressed the proliferative and clonogenic function of these cancerous cells. The flow cytometry results revealed that LINC00273 knockdown notably induced G0/G1 phase arrest in the ovarian cancer cells. LINC00273 knockdown also promoted E-cadherin expression in the ovarian cancer cells, and inhibited vimentin, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and N-cadherin, expression to inhibit the invasion and migration ability of the ovarian cancer cells. The in vivo experiments indicated that LINC00273 knockdown suppressed in vivo cancer cell proliferation in the ovaries. Conclusions: LINC00273 is highly expressed in both ovarian cancerous tissues and ovarian cancerous cell lines. LINC00273 knockdown greatly suppressed the proliferative and invasive capabilities of the cancerous ovarian cells. In terms of the molecular process, it may be that the knockdown of LINC00273 promotes E-cadherin and inhibits vimentin, N-cadherin, MMP-2, and MMP-9 expression in cancerous ovarian cells.
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BACKGROUND: Perjeta® is a recombinant, humanized monoclonal antibody that has been marketed and approved for the targeted therapy of human epidermal growth factor receptor (HER2) positive breast cancer in the United States. This study compared the bioequivalence, immunogenicity, and safety of pertuzumab injection (a biosimilar of Perjeta® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Perjeta® (produced by Roche Pharma AG) in healthy Chinese males. RESEARCH DESIGN AND METHODS: Healthy Chinese male subjects (N = 87) were randomly given intravenous injection of 5 mg/kg pertuzumab or Perjeta® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay, and primary pharmacokinetic parameters were statistically analyzed. We detected the levels of anti-drug antibody (ADA) and neutralizing antibody (nAb) to evaluate drug immunogenicity and safety of the drugs throughout the study. RESULTS: The geometric mean ratios of AUC0-t, Cmax, and AUC0-∞ for pertuzumab and Perjeta® were 100.42%, 96.71%, and 101.47%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. The levels of ADA and nAb were similar. In addition, both had good safety in the study. CONCLUSION: The study shows that pertuzumab injection and Perjeta® had similar bioequivalence, immunogenicity, and safety.