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Transcription of eukaryotic protein-coding genes generates immature mRNAs that are subjected to a series of processing events, including capping, splicing, cleavage, and polyadenylation (CPA), and chemical modifications of bases. Alternative polyadenylation (APA) greatly contributes to mRNA diversity in the cell. By determining the length of the 3' untranslated region, APA generates transcripts with different regulatory elements, such as miRNA and RBP binding sites, which can influence mRNA stability, turnover, and translation. In the model plant Arabidopsis thaliana, APA is involved in the control of seed dormancy and flowering. In view of the physiological importance of APA in plants, we decided to investigate the effects of light/dark conditions and compare the underlying mechanisms to those elucidated for alternative splicing (AS). We found that light controls APA in approximately 30% of Arabidopsis genes. Similar to AS, the effect of light on APA requires functional chloroplasts, is not affected in mutants of the phytochrome and cryptochrome photoreceptor pathways, and is observed in roots only when the communication with the photosynthetic tissues is not interrupted. Furthermore, mitochondrial and TOR kinase activities are necessary for the effect of light. However, unlike AS, coupling with transcriptional elongation does not seem to be involved since light-dependent APA regulation is neither abolished in mutants of the TFIIS transcript elongation factor nor universally affected by chromatin relaxation caused by histone deacetylase inhibition. Instead, regulation seems to correlate with changes in the abundance of constitutive CPA factors, also mediated by the chloroplast.
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Arabidopsis , Cloroplastos , Regulación de la Expresión Génica de las Plantas , Luz , Poliadenilación , Arabidopsis/genética , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Cloroplastos/genética , Empalme Alternativo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
The following study involved the utilization of dispersion polymerization to synthesize micron/nano-sized polystyrene (PS) spheres, which were then deposited onto a silicon substrate using the floating assembly method to form a long-range monolayer. Subsequently, dry etching techniques were utilized to create subwavelength structures. The adjustment of the stabilizer polyvinylpyrrolidone (PVP), together with changes in the monomer concentration, yielded PS spheres ranging from 500 nm to 5.6 µm in diameter. These PS spheres were suspended in a mixture of alcohol and deionized water before being arranged using the floating assembly method. The resulting tightly packed particle arrangement is attributed to van der Waals forces, Coulomb electrostatic forces between the PS spheres, and surface tension effects. The interplay of these forces was analyzed to comprehend the resulting structure. Dry etching, utilizing the PS spheres as masks, enabled the exploration of the effects of etching parameters on the resultant structures. Unlike traditional dry etching methods controlling RF power and etching gases, in the present study, we focused on adjusting the oxygen flow rate to achieve cylindrical, conical, and parabolic etched structures.
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BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.
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Asma , Alcoholes Bencílicos , Clorobencenos , Combinación de Medicamentos , Humanos , Masculino , Femenino , Alcoholes Bencílicos/administración & dosificación , Alcoholes Bencílicos/uso terapéutico , Estudios Retrospectivos , Asma/tratamiento farmacológico , Persona de Mediana Edad , Clorobencenos/administración & dosificación , Clorobencenos/uso terapéutico , Adulto , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Administración por Inhalación , Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Antiasmáticos/uso terapéutico , Antiasmáticos/administración & dosificación , Anciano , Fumarato de Formoterol/administración & dosificación , Resultado del Tratamiento , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Combinación Budesonida y Fumarato de Formoterol/administración & dosificación , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Pruebas de Función Respiratoria , Eosinófilos/efectos de los fármacosRESUMEN
BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.
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Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.
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COVID-19 , Interferones , Embarazo , Humanos , Femenino , Vacunas contra la COVID-19 , Quimiocina CXCL10 , Ligando Inductor de Apoptosis Relacionado con TNF , Mujeres Embarazadas , ChAdOx1 nCoV-19 , COVID-19/prevención & control , Vacunación , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
BACKGROUND: Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies. METHODS: We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed. RESULTS: Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%). CONCLUSIONS: Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature.
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Bocio Nodular , Tiroidectomía , Humanos , Femenino , Tiroidectomía/métodos , Tiroidectomía/efectos adversos , Adulto , Bocio Nodular/cirugía , Bocio Nodular/patología , Cirugía Endoscópica por Orificios Naturales/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Endoscopía/métodosRESUMEN
BACKGROUND: This study aimed to examine the clinical characteristics of bone metastasis (BoM) in patients with non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) mutation and to identify the most effective treatment strategy using EGFR-tyrosine kinase inhibitors (TKIs). METHODS: The study included patients with stage IV EGFR-mutated NSCLC who were receiving first-line treatment with EGFR-TKIs between January 2014 and December 2020. These patients were divided into two groups based on the presence or absence of BoM at the time of initial diagnosis. The BoM group was further subdivided based on whether they received denosumab or not. RESULTS: The final analysis included 247 patients. Those with BoM at initial diagnosis had shorter progression-free survival (12.6 vs. 10.5 months, p = 0.002) and overall survival (OS) (49.7 vs. 30.9 months, p = 0.002) compared to those without BoM. There was a difference in the location of metastatic sites between the two groups, with a higher incidence of extrathoracic metastasis in the BoM group (p < 0.001). The incidence of T790M was higher in patients with BoM than in those without (47.4% vs. 33.9%, p = 0.042). Multivariate Cox regression analysis revealed that sequential osimertinib treatment and the addition of antiangiogenic therapy (AAT) and denosumab therapy improved OS in patients with BoM. CONCLUSIONS: The presence of BoM is a negative prognostic factor for NSCLC patients with an EGFR mutation, possibly due to the presence of extrathoracic metastases. However, adding AAT and denosumab, along with sequential osimertinib, to the treatment regimen for patients with BoM can improve survival outcomes.
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Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Denosumab/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Mutación , Estudios RetrospectivosRESUMEN
This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.
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BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification. METHODS: Two cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III-IVA or stage I-II with positive pelvic or para-aortic lymph node (PALN) on PET/CT from AGOG09-001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer-specific survival (CSS) using multivariate Cox regression. RESULTS: Analysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p < 0.001, p = 0.014, and p = 0.026, respectively) with a median follow-up duration of 51 months. Assigning a score of 1 to each adverse predictor, patients with cumulative risk scores of 0, 1, 2, and 3 were discovered to have a 5-year CSS of 86.9%, 71.0%, 32.2%, and 0%, respectively (p < 0.001). CONCLUSION: Age, primary tumor MTV, and positive PALN on PET/CT may serve as independent predictors of poor survival in patients with locally advanced cervical SCC. Our findings indicate that patients without any adverse factors can receive standard CCRT, whereas those with at least one adverse factor can consider novel combination therapies or clinical trials.
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Carcinoma de Células Escamosas , Quimioradioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/diagnóstico por imagen , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Medición de Riesgo , Estadificación de Neoplasias , Fluorodesoxiglucosa F18 , Medicina de Precisión/métodos , Adulto , Carga TumoralRESUMEN
This pilot study explores alterations in miRNA profiles among pregnant women and their neonates upon receiving different doses of COVID-19 vaccines. Blood samples, including maternal blood (MB) and neonatal cord blood (CB), collected from five pregnant women were scrutinized using the miRNA PanelChip Analysis System, identifying nine distinct miRNAs, including miR-451a and miR-1972, which exhibited significant downregulation with two vaccine doses in both MB and CB. When compared with women vaccinated with four doses, miR-486-5p, miR-451a, and miR-1972 in the two-dose group also showed notable downregulation. Evaluating recipients of three and four doses, miR-423-5p and miR-1972 expression were significantly reduced in both MB and CB. Further comparative analysis highlighted a decline in miR-223-3p expression with increasing vaccine doses, while miR15a-5p, miR-16-5p, and miR-423-5p showed an upward trend. Notably, miR-451a, miR-1972, and miR-423-5p levels varied across doses and were associated with pathways such as "PI3K-Akt", "neurotrophin signaling", and "cortisol synthesis", suggesting the profound influence of vaccination on diverse molecular mechanisms. Our research has uncovered that escalating vaccine dosages impact miRNA profiles, which may be associated with the immunological response mechanisms in both the mother and fetus, thus indicating a substantial impact of vaccination on various molecular processes.
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Our study was to investigate the effects of bivalent COVID-19 booster vaccination during pregnancy on neutralizing antibody (Nab) levels in maternal blood (MB), transplacental transmission in umbilical cord blood (CB), and efficacy against Omicron SARS-CoV-2 subvariants including BA.5, BF.7, BQ.1, and XBB.1.5. We collected MB and CB from 11 pregnant participants during baby delivery and detected Nab inhibition by enzyme-linked immunosorbent assays (ELISA). Nab inhibition was 89-94% in MB and 82-89% in CB for Omicron subvariants. Those receiving AZD1222 vaccines in previous monovalent vaccination demonstrated poorer maternal Nab inhibition of BA.5, BQ.1, and XBB.1.5 than others. Poorer maternal Nab inhibition of BA.5, BF.7, and BQ.1 was found in those receiving two-dose AZD1222 vaccinations than with either one or no AZD1222 vaccination. MB from those with infants weighing < 3100 g demonstrated better Nab inhibition of BF.7 than those > 3100 g (97.99 vs. 95.20%, p = 0.048), and there were also similar trends for Nab inhibition of BA.5 and BQ.1. No significant differences were seen in CB samples. Although diminished maternal Nab inhibition was seen in those with previous monovalent AZD1222 vaccination and heavier newborns, neonatal Nab inhibition was still strong after bivalent COVID-19 booster vaccination.
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BACKGROUND: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population. METHODS: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images. RESULTS: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease. CONCLUSION: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients.
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Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Trastornos Respiratorios , Humanos , Adulto , Oscilometría , Enfermedades Pulmonares Intersticiales/diagnóstico , Pruebas de Función Respiratoria , Artritis Reumatoide/complicacionesRESUMEN
This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future.
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Hipertermia Inducida , MicroARNs , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Quimioterapia Intraperitoneal Hipertérmica , Quimiocina CCL5 , Inhibidor Tisular de Metaloproteinasa-1 , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/genética , Líquido Ascítico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interleucina-6/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Citocinas/uso terapéutico , MicroARNs/genética , MicroARNs/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Terapia Combinada , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.
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Virus del Dengue , Dengue , Dengue Grave , Ratones , Animales , FN-kappa B/metabolismo , Ciclooxigenasa 2/genética , Virus del Dengue/fisiología , Dengue Grave/tratamiento farmacológico , Replicación ViralRESUMEN
BACKGROUND AND OBJECTIVE: Taohong Siwu Decoction (TSD) is a classic traditional Chinese medicine (TCM) compound with pharmacological effects such as vasodilation and hypolipidemia. Paeoniflorin (PF) is one of the active ingredients of TSD. The aim of this study was to evaluate the pharmacokinetics of PF in herbal extracts and their purified forms in rats. METHOD: A sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method for the determination of PF in rat plasma was developed. Rats were divided into three groups, and given PF solution, water extract of white peony root (WPR), or TSD by gavage. At different predetermined timepoints after gavage, blood was collected from the orbital vein. The pharmacokinetic parameters of PF in the plasma of rats in the three groups was determined. RESULTS: The pharmacokinetic studies showed that the time to reach maximum concentration (Tmax) of PF in the purified forms group was relatively high, while the half-lives (T½) of PF in the TSD and WPR groups were longer. Among the three groups, PF in the purified forms group had the maximum area under the concentration-time curve (AUC0-t = 732.997 µg/L·h) and the largest maximum concentration (Cmax = 313.460 µg/L), which showed a significant difference compared with the TSD group (P < 0.05). Compared with the purified group, the clearance (CLz/F = 86.004 L/h/kg) and the apparent volume of distribution (Vz/F = 254.787 L/kg) of PF in the TSD group increased significantly (P < 0.05). CONCLUSIONS: A highly specific, sensitive, and rapid HPLC-MS-MS method was developed and applied for the determination of PF in rat plasma. It was found that TSD and WPR can prolong the action time of paeoniflorin in the body.
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Medicamentos Herbarios Chinos , Ratas , Animales , Ratas Sprague-Dawley , Cromatografía Líquida de Alta Presión/métodos , Administración OralRESUMEN
Background: No reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication. Methods: We collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated. Results: A total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm3, p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time (p = 0.001), treatment duration (p = 0.002), and ablated energy (p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm3/min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency (p = 0.067), treatment speed (p = 0.007), treatment efficiency (p = 0.001), NPV per energy (p = 0.005), and NPV per sonication (p = 0.004) than other 2 groups. Conclusion: Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results.
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This real-world study evaluated the efficacy of once-daily long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) for improving lung function in patients with chronic obstructive pulmonary disease (COPD). Patients with COPD who were treated with once-daily LABA/LAMA FDCs for 12 months were included. We evaluated their lung function improvement after 12 months of treatment with different LABA/LAMA FDCs. A total of 198 patients with COPD who were treated with once-daily LABA/LAMA FDCs were analyzed. A total of 114 patients were treated with umeclidinium/vilanterol (UMEC/VIL); 34 patients were treated with indacaterol/glycopyrronium (IND/GLY); and 50 patients were treated with tiotropium/olodaterol (TIO/OLO). The forced expiratory volume in 1 s (FEV1) was significantly increased in the patients treated with all three once-daily FDCs (55.2% to 60.9%, p = 0.012 for UMEC/VIL, 58.2% to 63.6%, p = 0.023 for IND/GLY, and 54.1% to 57.7%, p = 0.009 for TIO/OLO). The treatment of COPD patients with TIO/OLO resulted in a significant improvement in both forced vital capacity (FVC%) (71.7% to 77.9%, p = 0.009) and residual volume (RV%) (180.1% to 152.5%, p < 0.01) compared with those treated with UMEC/VIL (FVC%: 75.1% to 81.5%, p < 0.001; RV%:173.8% to 165.2%, p = 0.231) or IND/GLY (FVC%: 73.9% to 79.3%, p = 0.08; RV%:176.8% to 168.3%, p = 0.589). Patients treated with UMEC/VIL or TIO/OLO showed significant improvement in FVC. In addition, those receiving TIO/OLO also showed significant improvement in RV reduction.
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Hepatitis C virus (HCV) NS3/4A protease is an attractive target for direct-acting antiviral agents. Real-time tracking of the NS3/4A protease distribution and activity is useful for clinical diagnosis and disease management. However, no approach has been developed that can systemically detect NS3/4A protease activity or distribution. We designed a protease-activatable retention probe for tracking HCV NS3/4A protease activity via positron emission topography (PET) imaging. A cell-penetrating probe was designed that consisted of a cell-penetrating Tat peptide, HCV NS3/4A protease substrate, and a hydrophilic domain. The probe was labeled by fluorescein isothiocyanate (FITC) and 124I in the hydrophilic domain to form a TAT-ΔNS3/4A-124I-FITC probe. Upon cleavage at NS3/4A substrate, the non-penetrating hydrophilic domain is released and accumulated in the cytoplasm allowing PET or optical imaging. The TAT-ΔNS3/4A-FITC probe selectively accumulated in NS3/4A-expressing HCC36 (NS3/4A-HCC36) cells/tumors and HCV-infected HCC36 cells. PET imaging showed that the TAT-ΔNS3/4A-124I-FITC probe selectively accumulated in the NS3/4A-HCC36 xenograft tumors and liver-implanted NS3/4A-HCC36 tumors, but not in the control HCC36 tumors. The TAT-ΔNS3/4A-124I-FITC probe can be used to represent NS3/4 protease activity and distribution via a clinical PET imaging system allowing. This strategy may be extended to detect any cellular protease activity for optimization the protease-based therapies.
RESUMEN
Various optical components employed in biomedical applications have been fabricated using spider silk because of its superior properties, such as elasticity, tensile strength, biodegradability, and biocompatibility. In this study, a highly sensitive fiber optic sugar sensor is fabricated using metal-nanolayer-coated spider silk. The spider silk, which is directly collected from Nephila pilipes, a giant wood spider, is naturally a protein-based biopolymer with great flexibility, low attenuation, and easy functionalization. The surface of the spider silk-based fiber is coated with a metal nano-layer by using the glancing angle deposition technique. This fiber optic sugar sensor is based on the principle of the change in the refractive indices of sugar solutions. The attained experimental results show that the proposed sugar sensor is highly sensitive in the detection of fructose, sucrose, and glucose concentrations. This work may provide a new way to realize precise and sensitive online sugar measurements for point-of-care diagnostics.
RESUMEN
The focus of this study was to investigate the detection of neutralizing antibodies (Nabs) in maternal serum and cord blood as the targeted samples by employing a lateral flow immunoassay combined with a spectrum reader (LFI-SR) and the correlation of Nab protection against different types of SARS-CoV-2. We enrolled 20 pregnant women who were vaccinated with the Moderna (mRNA-1273) vaccine during pregnancy and collected 40 samples during delivery. We used an LFI-SR for the level of spike protein receptor binding domain antibody (SRBD IgG) as Nabs and examined the correlation of the SRBD IgG concentration and Nab inhibition rates (NabIR) via enzyme-linked immunosorbent assays (ELISA). The LFI-SR had high confidence for the SRBD IgG level (p < 0.0001). Better NabIR were found in wild-type SARS-CoV-2 (WT) compared to Delta-type (DT) and Omicron-type (OT). Women with two-dose vaccinations demonstrated greater NabIR than those with a single dose. The cut-off value of the SRBD IgG level by the LFI-SR for NabIR to DT (≥30%; ≥70%) was 60.15 and 150.21 ng/mL for mothers (both p = 0.005), and 156.31 (p = 0.011) and 230.20 ng/mL (p = 0.006) for babies, respectively. An additional vaccine booster may be considered for those mothers with SRBD IgG levels < 60.15 ng/mL, and close protection should be given for those neonates with SRBD IgG levels < 150.21 ng/mL, since there is no available vaccine for them.