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1.
Dev Biol ; 512: 57-69, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38750688

RESUMEN

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.

2.
Sci Total Environ ; 930: 172561, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38641104

RESUMEN

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.


Asunto(s)
Salinidad , Animales , Estrés Fisiológico , Bivalvos/fisiología , Estrés Salino
3.
Front Pharmacol ; 15: 1348076, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38572428

RESUMEN

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

4.
Ecotoxicol Environ Saf ; 277: 116339, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38669873

RESUMEN

Children's exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09-1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1-2.05). Comparing none (

Asunto(s)
Antibacterianos , Exposición a Riesgos Ambientales , Obesidad Infantil , Humanos , Estudios de Casos y Controles , Antibacterianos/efectos adversos , Masculino , Niño , Estudios Transversales , Femenino , Exposición a Riesgos Ambientales/estadística & datos numéricos , Obesidad Infantil/epidemiología , Obesidad Infantil/inducido químicamente , Contaminantes Ambientales/orina , Modelos Logísticos
5.
ACS Appl Mater Interfaces ; 16(14): 18124-18133, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38531041

RESUMEN

Surface-enhanced Raman scattering (SERS) presents a promising avenue for trace matter detection by using plasmonic nanostructures. To tackle the challenges of quantitatively analyzing trace substances in SERS, such as poor enrichment efficiency and signal reproducibility, this study proposes a novel approach using Au@internal standard@Au nanospheres (Au@IS@Au NSs) for realizing the high sensitivity and stability in SERS substrates. To verify the feasibility and stability of the SERS performances, the SERS substrates have exhibited exceptional sensitivity for detecting methyl blue molecules in aqueous solutions within the concentration range from 10-4 M to 10-13 M. Additionally, this strategy also provides a feasible way of quantitative detection of antibiotic in the range of 10-4 M to 10-10 M. Trace antibiotic residue on the surface of shrimp in aquaculture waters was successfully conducted, achieving a remarkably low detection limit of 10-9 M. The innovative approach has great potential for the rapid and quantitative detection of trace substances, which marks a noteworthy step forward in environmental detection and analytical methods by SERS.

6.
United European Gastroenterol J ; 12(2): 226-239, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38372444

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Resultado del Tratamiento , Inmunoterapia , Antineoplásicos/uso terapéutico
7.
Int J Cardiovasc Imaging ; 40(3): 601-611, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38183509

RESUMEN

BACKGROUND: Early identification of abnormal left ventricular function in children with obstructive sleep apnea (OSA) is difficult using conventional echocardiographic indices and commonly used clinical markers of myocardial damage. We sought to investigate the value of automatic function imaging and myocardial work parameters in predicting early cardiac impairment in children having OSA with preserved left heart function and thereby identifying an optimal index for assessment. PATIENTS AND METHODS: Fifty-two children who presented with symptoms of nocturnal sleep snoring and open-mouth breathing and 34 healthy controls were enrolled in this study. Clinical characteristics and conventional echocardiographic data were collected, and image analysis was performed using two-dimensional speckle-tracking echocardiography to obtain left ventricular global longitudinal strain (GLS), post-systolic index, peak strain dispersion, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. RESULTS: Children with OSA had significantly lower GLS, GWI, and GCW than those without (P < 0.05). Additionally, GWI (ß = -32.87, 95% CI: -53.47 to -12.27), and GCW (ß = -35.09, 95% CI: -55.35 to -14.84) were found to correlate with the disease severity in the multiple linear regression mode, with worsening values observed as the severity of the disease increased. ROC curve analysis revealed that GCW was the best predictor of myocardial dysfunction, with an AUC of 0.809 (P < 0.001), and the best cutoff point for diagnosing myocardial damage in children with OSA was 1965.5 mmHg%, with a sensitivity of 92.5% and a specificity of 58.7%. CONCLUSIONS: GLS, GWI, and GCW were identified as predictors of myocardial dysfunction in children with OSA, with GCW being the best predictor.


Asunto(s)
Apnea Obstructiva del Sueño , Disfunción Ventricular Izquierda , Niño , Humanos , Valor Predictivo de las Pruebas , Ecocardiografía/métodos , Sístole , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico por imagen , Función Ventricular Izquierda , Volumen Sistólico
8.
J Clin Transl Hepatol ; 12(1): 15-24, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38250466

RESUMEN

Background and Aims: Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC. Methods: A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Pooled effect estimates were calculated using a random effects model within the frequentist framework. Subgroup analyses based on etiology were also conducted. Results: Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included. OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305 [hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.80-1.68] and camrelizumab plus apatinib (HR: 1.06; 95% CI: 0.75-1.51). The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs. The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation. The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages (R2=0.8039, p=0.0155). Conclusion: This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology.

9.
J Org Chem ; 89(4): 2637-2648, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38277477

RESUMEN

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B2pin2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

10.
Nat Prod Res ; : 1-9, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38069504

RESUMEN

Three undescribed schinortriterpenoids, schinensilactones D-F (1-3), together with five known ones, namely, wuweizidilactone A (4), wuweizidilactone C (5), wuweizidilactone F (6), wuweizidilactone J (7) and wuweizidilactone N (8), were isolated from the leaves of Schisandra chinensis (Turcz.) Baill. The structures of new compounds were established by analysis of their spectroscopic data including MS, IR, 1D- and 2D-NMR spectra. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD) spectra. All compounds were evaluated for their neuroprotective effects against H2O2-induced injury in human neuroblastoma SH-SY5Y cell lines. Cell viability was remarkably reduced to 52.33% in H2O2-treated cells. Compounds 5-7 exhibited moderate neuroprotective activities at 50 µM, with cell viability of 64.84%, 67.34% and 63.73%, respectively.

11.
Environ Sci Pollut Res Int ; 30(58): 121823-121833, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37962761

RESUMEN

Children aged 3-6 years undergo a critical stage of growth and development and are irreversibly affected by their iodine status. In order to reveal iodine status in preschool children, we detected iodine concentrations in urine samples from 1382 children aged 3-6 years based on a cross-sectional study. The median urinary iodine concentration (UIC) of children was 193.36 µg/L and was 336.96 µg/g·Cr corrected for creatinine. The study developed a link between dietary habits and iodine status, revealing that regular calcium supplement (OR: 1.79, (95% CI: 1.03, 3.12)) increased deficiency risk, while moderate seafood consumption (OR: 0.60, (95% CI: 0.38, 0.95)) decreased it. Additionally, modest intake of shellfish (OR: 0.58, (95% CI: 0.33, 1.00)), vegetables (OR: 0.61, (95% CI: 0.38, 0.97)), and eggs (OR: 0.53, (95% CI: 0.30, 0.95)) was found to protect against excess iodine. The findings underline the importance of balanced diets and various nutrients' roles in preschoolers' iodine status.


Asunto(s)
Yodo , Humanos , Preescolar , Estudios Transversales , China , Nutrientes , Alimentos Marinos , Estado Nutricional
12.
Front Biosci (Landmark Ed) ; 28(9): 226, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37796688

RESUMEN

BACKGROUND: In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. METHODS: We surgically induced chronic kidney disease in C57BL/6J male mice aged 8-9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. RESULTS: Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein-interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.


Asunto(s)
Lacticaseibacillus rhamnosus , Probióticos , Insuficiencia Renal Crónica , Masculino , Animales , Ratones , Interleucina-6 , Ratones Endogámicos C57BL , Riñón/fisiología , Insuficiencia Renal Crónica/terapia , Probióticos/farmacología , Probióticos/uso terapéutico , Biomarcadores
13.
Sci Total Environ ; 905: 166834, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-37717744

RESUMEN

The herbicide ioxynil (IOX) and the synthetic estrogen diethylstilbestrol (DES) are environmentally relevant contaminants that act as endocrine disruptors (EDCs) and have recently been shown to be cardiovascular disruptors in vertebrates. Mussels, Mytilus coruscus, were exposed to low doses of IOX (0.37, 0.037 and 0.0037 mg/L) and DES (0.27, 0.027 and 0.0027 mg/L) via the water and the effect monitored by generating whole animal transcriptomes and measuring cardiac performance and shell growth. One day after IOX (0.37 and 0.037 mg/L) and DES (0.27 and 0.027 mg/L) exposure heart rate frequency was decreased in both groups and 0.27 mg/L DES significantly reduced heart rate frequency with increasing time of exposure (P < 0.05) and no acclimatization occurred. The functional effects were coupled to significant differential expression of genes of the serotonergic synapse pathway and cardiac-related genes at 0.027 mg/L DES, which suggests that impaired heart function may be due to interference with neuroendocrine regulation and direct cardiac effect genes. Multiple genes related to detoxifying xenobiotic substances were up regulated and genes related to immune function were down regulated in the DES group (vs. control), indicating that detoxification processes were enhanced, and the immune response was depressed. In contrast, IOX had a minor disrupting effect at a molecular level. Of note was a significant suppression (P < 0.05) by DES of shell growth in juveniles and lower doses (< 0.0027 mg/L) had a more severe effect. The shell growth depression in 0.0027 mg/L DES-treated juveniles was not accompanied by abundant differential gene expression, suggesting that the effect of 0.0027 mg/L DES on shell growth may be direct. The results obtained in the present study reveal for the first time that IOX and DES may act as neuroendocrine disrupters with a broad spectrum of effects on cardiac performance and shell growth, and that DES exposure had a much more pronounced effect than IOX in a marine bivalve.


Asunto(s)
Dietilestilbestrol , Mytilus , Animales , Dietilestilbestrol/toxicidad , Dietilestilbestrol/metabolismo , Corazón , Nitrilos/metabolismo , Yodobencenos
14.
J Integr Med ; 21(5): 487-495, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37544834

RESUMEN

OBJECTIVE: This study tests the efficacy of Bletilla striata polysaccharide (BSP), carboxymethyl chitosan (CMC), baicalin (BA) and silver titanate (ST) in a wound dressings to fight infection, promote healing and provide superior biocompatibility. METHODS: The antibacterial activity of BA and ST was evaluated in vitro using the inhibition zone method. BA/ST/BSP/CMC porous sponge dressings were prepared and characterized. The biocompatibility of BA/ST/BSP/CMC was assessed using the cell counting kit-8 assay. The therapeutic effect of BA/ST/BSP/CMC was further investigated using the dorsal skin burn model in Sprague-Dawley rats. RESULTS: The wound dressing had good antibacterial activity against Escherichia coli and Staphylococcus aureus through BA and ST, while the combination of BSP and CMC played an important role in promoting wound healing. The BA/ST/BSP/CMC porous sponge dressings were prepared using a freeze-drying method with the concentrations of BA and ST at 20 and 0.83 mg/mL, respectively, and the optimal ratio of 5% BSP to 4% CMC was 1:3. The average porosity, water absorption and air permeability of BA/ST/BSP/CMC porous sponge dressings were measured to be 90.43%, 746.1% and 66.60%, respectively. After treatment for 3 and 7 days, the healing rates of the BA/ST/BSP/CMC group and BA/BSP/CMC group were significantly higher than those of the normal saline (NS) group and silver sulfadiazine (SSD) group (P < 0.05). Interleukin-1ß expression in the BA/ST/BSP/CMC group at 1 and 3 days was significantly lower than that in the other three groups (P < 0.05). After being treated for 3 days, vascular endothelial growth factor expression in the BA/BSP/CMC group and BA/ST/BSP/CMC group was significantly higher than that in the NS group and SSD group (P < 0.05). Inspection of histological sections showed that the BA/ST/BSP/CMC group and BA/BSP/CMC group began to develop scabbing and peeling of damaged skin after 3 days of treatment, indicating accelerated healing relative to the NS group and SSD group. CONCLUSION: The optimized concentration of BA/ST/BSP/CMC dressing was as follows: 6 mg BSP, 14.4 mg CMC, 0.5 mg ST and 12 mg BA. The BA/ST/BSP/CMC dressing, containing antibacterial constituents, was non-cytotoxic and effective in accelerating the healing of burn wounds, making it a promising candidate for wound healing. Please cite this article as: Gong YR, Zhang C, Xiang X, Wang ZB, Wang YQ, Su YH, Zhang HQ. Baicalin, silver titanate, Bletilla striata polysaccharide and carboxymethyl chitosan in a porous sponge dressing for burn wound healing. J Integr Med. 2023; 21(5): 487-495.


Asunto(s)
Quemaduras , Quitosano , Ratas , Animales , Quitosano/farmacología , Plata/farmacología , Porosidad , Factor A de Crecimiento Endotelial Vascular/farmacología , Ratas Sprague-Dawley , Cicatrización de Heridas , Polisacáridos/farmacología , Vendajes , Quemaduras/tratamiento farmacológico , Antibacterianos/farmacología , Sulfadiazina de Plata/farmacología
15.
Environ Sci Pollut Res Int ; 30(39): 90980-90992, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37468774

RESUMEN

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.


Asunto(s)
Mercurio , Femenino , Embarazo , Humanos , Estudios Transversales , China , Mercurio/análisis , Factores de Riesgo , Conducta Alimentaria
16.
Eur Radiol ; 33(12): 8669-8681, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37368105

RESUMEN

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Antineoplásicos/uso terapéutico , Quimioembolización Terapéutica/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos
17.
18.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2868-2875, 2023 Jun.
Artículo en Chino | MEDLINE | ID: mdl-37381949

RESUMEN

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.


Asunto(s)
Medicina , Biología de Sistemas , Humanos , Diseño de Fármacos , Desarrollo de Medicamentos , Genómica
19.
World J Clin Cases ; 11(5): 1188-1197, 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36874427

RESUMEN

BACKGROUND: Littoral cell angioma (LCA) is a rare benign vascular tumor of the spleen. Given its rarity, standard diagnostic and therapeutic recommendations have yet to be developed for reported cases. Splenectomy is the only method of obtaining a pathological diagnosis and providing treatment to obtain a favorable prognosis. CASE SUMMARY: A 33-year-old female presented with abdominal pain for one month. Computed tomography and ultrasound revealed splenomegaly with multiple lesions and two accessory spleens. The patient underwent laparoscopic total splenectomy and accessory splenectomy, and splenic LCA was confirmed by pathology. Four months after surgery, the patient presented with acute liver failure, was readmitted, rapidly progressed to multiple organ dysfunction syndrome and died. CONCLUSION: Preoperative diagnosis of LCA is challenging. We systematically reviewed online databases to identify the relevant literature and found a close relationship between malignancy and immunodysregulation. When a patient suffers from both splenic tumors and malignancy or immune-related disease, LCA is possible. Due to potential malignancy, total splenectomy (including accessory spleen) and regular follow-up after surgery are recommended. If LCA is diagnosed after surgery, a comprehensive postoperative examination is needed.

20.
Genes (Basel) ; 14(2)2023 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-36833215

RESUMEN

Many marine invertebrate larvae undergo complex morphological and physiological changes during the planktonic-benthic transition (a.k.a. metamorphosis). In this study, transcriptome analysis of different developmental stages was used to uncover the molecular mechanisms underpinning larval settlement and metamorphosis of the mussel, Mytilus coruscus. Analysis of highly upregulated differentially expressed genes (DEGs) at the pediveliger stage revealed enrichment of immune-related genes. The results may indicate that larvae co-opt molecules of the immune system to sense and respond to external chemical cues and neuroendocrine signaling pathways forecast and trigger the response. The upregulation of adhesive protein genes linked to byssal thread secretion indicates the anchoring capacity required for larval settlement arises prior to metamorphosis. The results of gene expression support a role for the immune and neuroendocrine systems in mussel metamorphosis and provide the basis for future studies to disentangle gene networks and the biology of this important lifecycle transformation.


Asunto(s)
Mytilus , Animales , Mytilus/genética , Transcriptoma , Plancton , Estadios del Ciclo de Vida , Metamorfosis Biológica/genética , Larva
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