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1.
Pharm Biol ; 62(1): 472-479, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38769628

RESUMEN

CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.


Asunto(s)
Enfermedades de la Mama , Medicamentos Herbarios Chinos , Hiperplasia , Medicina Tradicional China , Humanos , Femenino , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Enfermedades de la Mama/tratamiento farmacológico , Medicina Tradicional China/métodos , China
2.
Heliyon ; 10(7): e29290, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38601636

RESUMEN

The incidence of lung cancer, especially lung adenocarcinoma (LUAD), has recently increased. Targeted therapy and immunotherapy combined with conventional treatment have shown surprising benefits in enhancing the LUAD patient's prognosis. For the purpose of guiding treatment planning and the prognosis of LUAD, more research is required. The particular aim of this work was to establish a purine metabolism scoring (PMS) model for the purpose of individually forecasting treatment outcomes and overall survival for patients who have LUAD. Clinical and whole genome data were obtained from the TCGA-LUAD cohort via "UCSC". The 25 driver purine metabolism-related prognostic genes were determined founded on univariate Cox regression. Then PMS was developed through stepwise LASSO Cox regression. Survival analysis indicated that patients who have PMS experienced worse outcomes. We validated the PGM2 effect on lung adenocarcinoma malignancy in in vitro experiments. Univariate as well as multivariate Cox regression suggested that PMS was an independent prognostic indicator for LUAD patients, which was confirmed in subgroup analysis. Functional assay demonstrated that immune response as well as cytotoxicity pathways have a connection with lower PMS, and patients who have low PMS possess an active immune microenvironment. Moreover, the LUAD patients who have low PMS showed greater sensitivity to immunotherapy, targeted therapy, as well as chemotherapy. Knockdown of PGM2 was discovered to decrease the proliferation, invasion, as well as migration of lung adenocarcinoma cells in an in vitro assay. Pertaining to this particular research, we created a PMS model and conducted a thorough analysis of purine metabolism in LUAD in order to determine prognosis and offer recommendations for treatment. This finding offered a fresh concept for the clinical management of LUAD and novel therapy protocols.

4.
Int J Hyperthermia ; 41(1): 2338542, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38684224

RESUMEN

OBJECTIVE: To investigate the changes in liver and kidney function, red blood cell (RBC) count and hemoglobin (HGB) levels in patients undergoing ultrasound-guided percutaneous microwave ablation (UPMWA) for uterine fibroids on postoperative day 1. METHODS: The changes in liver and kidney function, RBC count and HGB levels in 181 patients who underwent selective UPMWA in the Second Affiliated Hospital of Shantou University Medical College, China, between August 2017 and January 2023 were retrospectively analyzed. RESULTS: All patients underwent UPMWA for uterine fibroids; 179 patients had multiple uterine fibroids and 2 patients had single uterine fibroids. The maximum fibroid diameter ranged from 18 to 140 mm, with an average of 68.3 mm. Ultrasound imaging was used to confirm that the blood flow signal within the mass had disappeared in all patients, indicating that the ablation was effective. Within 24 h, compared with before UPMWA, levels of total bilirubin, direct bilirubin, indirect bilirubin and aspartate aminotransferase had significantly increased (p < 0.01), whereas levels of total protein, albumin, globulin, alanine aminotransferase, creatinine and urea had significantly decreased (p < 0.01). Acute kidney injury (AKI) occurred in 1 of the 181 patients. The RBC count and HGB levels decreased significantly after UPMWA (p < 0.01). CONCLUSION: Ultrasound-guided percutaneous microwave ablation for uterine fibroids can impose a higher detoxification load on the liver and cause thermal damage to and the destruction of RBCs within local circulation, potentially leading to AKI. Protein levels significantly decreased after UPMWA. Therefore, perioperative organ function protection measures and treatment should be actively integrated into clinical practice to improve prognosis and enhance recovery.


Asunto(s)
Hemoglobinas , Leiomioma , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/sangre , Leiomioma/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Recuento de Eritrocitos , Riñón/diagnóstico por imagen , Riñón/cirugía , Hígado/diagnóstico por imagen , Hígado/metabolismo , Hígado/cirugía , Estudios Retrospectivos , Microondas/uso terapéutico
5.
Biochem Biophys Res Commun ; 706: 149747, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38479243

RESUMEN

Nobiletin is a natural flavonoid found in citrus fruits with beneficial effects, including anti-inflammatory, anti-cancer and anti-oxidation effects. The aim of this study was to investigate whether nobiletin improves mitochondrial function in porcine oocytes and examine the underlying mechanism. Oocytes enclosed by cumulus cells were cultured in TCM-199 for 44 h with 0.1% dimethyl sulfoxide (control), or supplemented with 5, 10, 25, and 50 µM of nobiletin (Nob5, Nob10, Nob25, and Nob50, respectively). Oocyte maturation rate was significantly enhanced in Nob10 (70.26 ± 0.45%) compared to the other groups (control: 60.12 ± 0.47%; Nob5: 59.44 ± 1.63%; Nob25: 63.15 ± 1.38%; Nob50: 46.57 ± 1.19%). The addition of nobiletin reduced the levels of reactive oxygen species and increased glutathione levels. Moreover, Nob10 promoted mitochondrial biogenesis by upregulating the protein levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α). This resulted in an increase in the number of active mitochondria, mitochondrial DNA copy number, mitochondrial membrane potential, and ATP production, thereby enhancing mitochondrial function. The protein level of p53 decreased, followed by the phosphorylation of B-cell lymphoma 2, suggesting a reduction in mitochondria-mediated apoptosis in the Nob10 group. Additionally, the release of cytochrome c from the mitochondria was significantly diminished along with a decrease in the protein expression of caspase 3. Thus, nobiletin has a great potential to promote the in vitro maturation of porcine oocytes by suppressing oxidative stress and promoting mitochondrial function through the upregulation of the SIRT1/PGC-1α signaling pathway.


Asunto(s)
Flavonas , Mitocondrias , Sirtuina 1 , Animales , Porcinos , Sirtuina 1/metabolismo , Mitocondrias/metabolismo , Transducción de Señal , Oocitos/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo
6.
Br J Anaesth ; 132(5): 877-885, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38429209

RESUMEN

BACKGROUND: Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. METHODS: In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from -5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥-2), moderate (RASS =-3), and deep sedation (RASS ≤-4) was assessed by areas under receiver operating characteristic (ROC) curves. RESULTS: A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17-25%) to 36% (interquartile range 33-40%) (P<0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. CONCLUSIONS: Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients.


Asunto(s)
Enfermedad Crítica , Hipnóticos y Sedantes , Adulto , Humanos , Estudios Prospectivos , Sedación Consciente , Electroencefalografía
7.
Artículo en Inglés | MEDLINE | ID: mdl-38416803

RESUMEN

Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Humanos , Ratones , Animales , Anciano , Enfermedad de la Arteria Coronaria/genética , Células Endoteliales/metabolismo , Estudio de Asociación del Genoma Completo , Ratones Noqueados para ApoE , Aterosclerosis/genética , Proteínas , Senescencia Celular
8.
Bioorg Med Chem ; 100: 117630, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38330849

RESUMEN

Tirzepatide, the first approved dual GLP-1/GIP receptor agonist (RA), has achieved better clinical outcomes than other GLP-1RAs. However, it is an imbalanced dual GIP/GLP-1 RA, and it remains unclear whether the degree of imbalance is optimal. Here, we present a novel long-acting dual GLP-1/GIP RA that exhibits better activity than tirzepatide toward GLP-1R. A candidate conjugate, D314, identified via peptide design, synthesis, conjugation, and experimentation, was evaluated using chronic studies in db/db and diet induced obese (DIO) mice. D314 achieved favorable blood glucose and body weight-lowering effects, equal to those of tirzepatide. Its half-life in dogs (T1/2: 78.3 ± 14.01 h) reveals its suitability for once-weekly administration in humans. This preclinical study suggests the potential role of D314 as an effective agent for treating T2DM and obesity.


Asunto(s)
Diabetes Mellitus Tipo 2 , Péptido 1 Similar al Glucagón , Receptores de la Hormona Gastrointestinal , Animales , Perros , Humanos , Ratones , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/farmacología , Obesidad/tratamiento farmacológico , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de la Hormona Gastrointestinal/uso terapéutico
9.
Heliyon ; 10(3): e25733, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38352762

RESUMEN

Drug-resistant N. gonorrhoeae is an urgent threat to global public health, and vaccine development is the best long-term strategy for controlling gonorrhea. We have previously shown that adhesion and penetration protein (App) play a role in the adhesion, invasion, and reproductive tract colonization of N. gonorrhoeae. Here, we describe the immune response induced by intranasal immunization with passenger and translocator fragments of App. The recombinant App passenger and translocator fragments induced high titers of IgG and IgA antibodies in serum and vaginal washes. Antibodies produced by App passenger and the combination of passenger and translocator mediated the killing of N. gonorrhoeae via serum bactericidal activity and opsonophagocytic activity, whereas antisera from translocator-immunized groups had lower bactericidal activity and opsonophagocytic activity. The antisera of the App passenger and translocator, alone and in combination, inhibited the adhesion of N. gonorrhoeae to cervical epithelial cells in a concentration-dependent manner. Nasal immunization with App passenger and translocator fragments alone or in combination induced high levels of IgG1, IgG2a, and IgG2b antibodies and stimulated mouse splenocytes to secrete cytokines IFN-γ and IL-17A, suggesting that Th1 and Th17 cellular immune responses were activated. In vivo experiments have shown that immune App passenger and transporter fragments can accelerate the clearance of N. gonorrhoeae in the vagina of mice. These data suggest that the App protein is a promising N. gonorrhoeae vaccine antigen.

10.
J Med Virol ; 96(2): e29451, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38305046

RESUMEN

Persistent human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer, posing serious threats to the health of women. Although the cervicovaginal microbiota is strongly associated with CIN, the dynamics of the microbiota during CIN development are unknown. In this retrospective cohort study, we analyzed 3-year longitudinal data from 72 patients diagnosed with a persistent HPV infection almost all caused by high-risk HPV types. Patients were categorized into groups with HPV persistent infection (n = 37), progression to CIN (n = 16), and CIN regression (n = 19) based on infection outcome during the follow-up period. Furthermore, 16S rRNA gene sequencing was performed on consecutively collected cervical samples to explore the composition and dynamics of the cervicovaginal microbiota during the development and regression of CIN. Our results showed that the composition of the cervicovaginal microbiota varied among women with different HPV infection outcomes and remained relatively stable during the follow-up period. Notably, the serial follow-up data showed that these microbial alterations were present for at least 1-2 years and occurred before pathologic changes. In addition, microbial markers that were highly discriminatory for CIN progression or regression were identified. This study provides evidence for a temporal relationship between changes in the cervicovaginal microbiota and the development of CIN, and our findings provide support for future microbial intervention strategies for CIN.


Asunto(s)
Microbiota , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , ARN Ribosómico 16S/genética , Estudios Retrospectivos , Cuello del Útero , Microbiota/genética , Papillomaviridae/genética
11.
J Pain Res ; 17: 11-19, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38192365

RESUMEN

Purpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section. Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥4) and control group (<4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia. Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P<0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913-19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356-0.604), extraversion (OR=0.667, 95% CI=0.513-0.866), neuroticism (OR=1.427, 95% CI=1.104-1.844), and PCS (OR=7.718, 95% CI=0.657-0.783) were factors affecting postoperative analgesia. Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.

12.
J Hazard Mater ; 465: 133468, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38219584

RESUMEN

Microporous organic networks (MONs) are highly porous materials that are particularly useful in analytical chemistry. However, the use of these materials is often limited by the functional groups available on their surface. Here, we described the polymerization of a sea urchin-like structure material at ambient temperature, that was functionalized with hydroxyl, carboxyl, and triazine groups and denoted as OH-COOH-MON-TEPT. A substantial proportion of OH-COOH-MON-TEPT was intricately decorated EDA-Fe3O4, creating a well-designed configuration (EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC) for superior adsorption of the target analytes phenylurea herbicides (PUHs) via magnetic solid-phase extraction (MSPE). The proposed method showed remarkably low limits of detection ranging from 0.03 to 0.22 ng·L-1. Experimental investigations and theoretical analyses unveiled the adsorption mode between EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC and PUHs. These findings establish a robust foundation for potential applications of EDA-Fe3O4 @OH-COOH-MON-TEPT-EDC in the analysis of various polar contaminants.

13.
Plant Physiol Biochem ; 207: 108340, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199025

RESUMEN

NIN-like proteins (NLPs) are evolutionarily conserved transcription factors that are unique to plants and play a pivotal role in responses to nitrate uptake and assimilation. However, a comprehensive analysis of NLP members in tea plants is lacking. The present study performed a genome-wide analysis and identified 33 NLP gene family members of Camellia sinensis that were distributed unequally across 5 chromosomes. Subcellular localisation predictions revealed that all CsNLP proteins were localised in the nucleus. Conservative domain analysis revealed that all of these proteins contained conserved RWP-RK and PB1 domains. Phylogenetic analysis grouped the CsNLP gene family into four clusters. The promoter regions of CsNLPs harboured cis-acting elements associated with plant hormones and abiotic stress responses. Expression profile analysis demonstrated that CsNLP8 was significantly upregulated in roots under nitrate stress conditions. Subcellular localisation analysis found CsNLP8 localised to the nucleus. Dual-luciferase reporter assay demonstrated that CsNLP8 positively regulated the expression of a nitrate transporter gene (CsNRT2.2). These findings provide a comprehensive characterisation of NLP genes in Camellia sinensis and offer insights into the biological function of CsNLP8 in regulating the response to nitrate-induced stress.


Asunto(s)
Camellia sinensis , Nitratos , Nitratos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Camellia sinensis/genética , Camellia sinensis/metabolismo , Filogenia , , Regulación de la Expresión Génica de las Plantas
14.
Pest Manag Sci ; 80(3): 1400-1411, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37933450

RESUMEN

BACKGROUND: Diapause is an environmentally preprogrammed period of arrested development that is important to insect survival and population growth. Histone acetylation, an epigenetic modification, has several biological functions, but its role in agricultural pest diapause is unknown. In this study, we investigated the role of histone H3 acetylation in the diapause of Helicoverpa armigera. RESULTS: The histone H3 gene of H. armigera was cloned, and multiple sequence alignment of amino acids revealed that the potential lysine acetylation sites were highly conserved across species. Investigation of histone H3 acetylation levels in diapause- and nondiapause-type pupae showed that acetylation levels were down-regulated in diapause-type pupae and were lower in diapausing pupae compared to nondiapause pupae. By screening the genome, six histone acetyltransferase (HAT) and eight histone deacetylase (HDAC) genes responsible for antagonizing catalytic histone acetylation modifications were identified in H. armigera, and most of them exhibited different expression patterns between diapause- and nondiapause-type pupae. To elucidate the effect of histone H3 acetylation on diapause in H. armigera, the diapause pupae were injected with the histone acetylation activator trichostatin A (TSA). The results indicated that TSA injection increased the levels of histone H3 acetylation, causing the diapausing pupae to revert to development. Furthermore, transcriptome analysis revealed that 259 genes were affected by TSA injection, including genes associated with metabolism, resistance, and immunological responses. CONCLUSION: These results suggest that histone acetylation is inseparably related to the pupal diapause of H. armigera, which promises to be a potential target for pest control. © 2023 Society of Chemical Industry.


Asunto(s)
Diapausa , Mariposas Nocturnas , Animales , Histonas/metabolismo , Helicoverpa armigera , Pupa , Acetilación
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123784, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38128325

RESUMEN

Cr3+-free near-infrared (NIR) phosphors are currently gaining significant attention in various application fields. A novel Fe3+-activated LiAlO2 NIR phosphor was successfully synthesized by high-temperature solid-state method. Under excitation of 391 nm and 467 nm, the phosphor emits near-infrared light with wavelengths ranging from 600 to 850 nm. The emission bands with peaks at 725 nm correspond to the transition from 4T1(4G) to the ground state energy level 6A1(6S). The optical band gap of LiAlO2 was calculated using Density Function Theory (DFT) and diffuse reflectance spectrum, respectively. The thermal stability of the sample was measured under 391 nm and 467 nm excitation, showing that the emission intensity at 413 K is 55.3 % and 52.4 % of the emission intensity at room temperature.

16.
Bioconjug Chem ; 34(12): 2366-2374, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38037956

RESUMEN

Bulevirtide, an entry inhibitor for the hepatitis B virus (HBV) and hepatitis D virus (HDV), is currently available on the European market. However, its clinical application is constrained by its short half-life and poor water solubility, rendering it unsuitable for fatty acid modification, aimed at achieving long-term effects. To address this limitation, we integrated a polypeptide chain consisting of Pro, Ala, and Ser at the C-terminus, which increased its hydrophilicity. To obtain the fusion sequence of A1 and A2, encompassing amino acids 1-47 of Bulevirtide and PAS, we used Escherichia coli fermentation expression. Subsequently, the N-terminal myristoyl groups of A1 and A2 were modified to yield Myr-A1 and Myr-A2, respectively. Five fatty acid moieties with the same hydrophilic spacers and different fatty acids were conjugated to analogs, generating 10 bioconjugations. The bioconjugates were then evaluated for their anti-HBV activity. Among them, HB-10 was selected for pharmacokinetic analysis and demonstrated a significantly prolonged half-life, with 5.88- and 13.18-fold increases in beagle dogs and rats, respectively. Additionally, higher drug doses resulted in substantially elevated liver concentrations. In conclusion, via fatty acid incorporation and PASylation, we successfully developed a novel Bulevirtide bioconjugate, HB-10, that exhibits an extended action duration. This compound holds substantial promise as a prospective long-acting entry inhibitor, warranting further investigation.


Asunto(s)
Ácidos Grasos , Virus de la Hepatitis B , Animales , Ratas , Perros , Ácidos Grasos/metabolismo , Estudios Prospectivos , Hígado/metabolismo , Virus de la Hepatitis Delta , Antivirales/farmacología , Antivirales/metabolismo
18.
Medicine (Baltimore) ; 102(48): e36410, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38050264

RESUMEN

Glioma is the most malignant tumor in the central nervous system with a poor prognosis. The tumor immune microenvironment plays a crucial role in glioma formation and progress. TREM1, as a vital immune regulator, has not been investigated in glioma. This study aims to explore the role of TREM1 in prognosis and tumor immune microenvironment of glioma. The mRNA expression level of TREM1 was collected from TCGA and GEO databases. The correlations between the clinic-pathological features and TREM1 expression were analyzed using Cox regression analysis. Kaplan-Meier was used to evaluate the effect of TREM1 on OS. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes were performed to analyze the functional annotations and signaling pathways of the TREM1 coexpression genes. ESTIMATE and TIMER explored the correlations between TREM1 and immune cell infiltration. Spearman correlation analysis was conducted to examine the association between the TREM1 and immune checkpoint expression. The expression level of TREM1 was significantly increased in glioma. TREM1 overexpression was positively related to poor prognosis, higher World Health Organization grade, isocitrate dehydrogenase wildtype, and 1p/19q non-codeletion. TREM1 coexpression genes were mainly related to immunoregulation and inflammatory response. TREM1 participated in the initiation and progression of glioma by regulating immune cell infiltration and expression of immune checkpoints. TREM1 is an effective prognostic and diagnostic biomarker in glioma. It can be adopted as a novel predictor for clinical prognosis, pathological characteristics, and immune microenvironment in glioma patients.


Asunto(s)
Glioma , Humanos , Pronóstico , Receptor Activador Expresado en Células Mieloides 1/genética , Glioma/genética , Sistema Nervioso Central , Aberraciones Cromosómicas , Biomarcadores , Microambiente Tumoral/genética
19.
Artículo en Inglés | MEDLINE | ID: mdl-37997804

RESUMEN

BACKGROUND: Patient-derived organoids (PDOs) are ex vivo models that retain the functions and characteristics of individualized source tissues, including a simulated tumor microenvironment. However, the potential impact of undiscovered differences between tissue sources on PDO growth and progression remains unclear. OBJECTIVE: This study aimed to compare the growth and condition of PDO models originating from surgical resection and colonoscopy and to provide practical insights for PDO studies. METHODS: Tissue samples and relevant patient clinical information were collected to establish organoid models. PDOs were derived from both surgical and colonoscopy tissues. The growth of the organoids, including their state, size, and success rate of establishment, was recorded and analyzed. The activity of the organoids at the end stage of growth was detected using calcein-AM fluorescence staining. RESULTS: The results showed that the early growth phase of 2/3 colonoscopy-derived organoids was faster compared to surgical PDOs, with a growth difference observed within 11-13 days of establishment. However, colonoscopy-derived organoids exhibited a diminished growth trend after this time. There were no significant differences observed in the terminal area and quantity between the two types of tissue-derived organoids. Immunofluorescence assays of the PDOs revealed that the surgical PDOs possessed a denser cell mass with relatively higher viability than colonoscopy-derived PDOs. CONCLUSION: In the establishment of colorectal patient-derived organoids, surgically derived organoids require a slightly longer establishment period, while colonoscopy-derived organoids should be passaged prior to growth inhibition to preserve organoid viability.

20.
Front Psychol ; 14: 1303942, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023034

RESUMEN

[This corrects the article DOI: 10.3389/fpsyg.2021.585666.].

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