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1.
PLoS One ; 19(8): e0308673, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39137209

RESUMO

OBJECTIVE: Relative to explicit absenteeism, nurses' presenteeism has a more lasting impact and is more harmful and costly. This study aimed to explore the relationship between work-family conflict, perceived social support, and presenteeism and whether perceived social support mediates the relationship between work-family conflict and presenteeism among ICU nurses working on shifts in Chinese public hospitals. MATERIALS AND METHODS: A cross-sectional research design was conducted from January to April 2023 in Sichuan Province, China. A total of 609 valid questionnaires were collected. The questionnaires contained information on demographic characteristics, the Work-Family Conflict (WFC) scale, the Perceived Social Support Scale (PSSS), and Stanford Presenteeism Scale-6 (SPS-6). Multiple stratified regression was used to explore the mediating role of perceived social support between work-family conflict and presenteeism. The mediating effect of perceived social support in work-family conflict and presenteeism was tested by Model 4 in the PROCESS 4.1 macro program in SPSS. RESULTS: A total of 609 nurses were included in this study, and the mean presenteeism score for ICU nurses working on shifts was 16.01 ± 4.293 (Mean ± SD), with high presenteeism accounting for 58.46%. After controlling for sociodemographic characteristic variables, work-family conflict was positively associated with presenteeism, explaining 7.7% of the variance. High perceived social support was related to low presenteeism, explaining 11.5% of the variance. Perceived social support mediated the association between work-family conflict and presenteeism among ICU nurses working on shifts. CONCLUSIONS: Chinese shift-work ICU nurses' high presenteeism scores deserve managers' attention. Work-family conflict is a significant predictor of nurses' presenteeism. Perceived social support is essential in improving nurses' work-family conflict and mediates the relationship between work-family conflict and presenteeism. Improving social support can reduce the impact of work-family conflict on presenteeism among nurses working shifts.


Assuntos
Hospitais Públicos , Unidades de Terapia Intensiva , Presenteísmo , Apoio Social , Humanos , Feminino , Adulto , Estudos Transversais , Masculino , Presenteísmo/estatística & dados numéricos , China , Inquéritos e Questionários , Recursos Humanos de Enfermagem Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Pessoa de Meia-Idade , Enfermagem de Cuidados Críticos , Enfermeiras e Enfermeiros/psicologia , Família/psicologia
2.
Virology ; 598: 110196, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39098183

RESUMO

Reovirus (Reo) has shown promising potential in specifically killing tumor cells, and offering new possibilities for ovarian cancer (OC) treatment. However, neutralizing antibodies in the ascites from OC patients greatly limit the further application of Reo. In this study, we employed cationic liposomes (Lipo) to deliver Reo, significantly enhancing its ability to enter OC cells and its effectiveness in killing these cells under ascitic conditions. Pre-treatment with the MßCD inhibitor notably decreased Reo-mediated tumor cell death, indicating that Lipo primarily enables Reo's cellular uptake through caveolin-mediated endocytosis. Our results demonstrate that Lipo effectively facilitates the entry of Reo into the cytoplasm and triggers cell apoptosis. The above findings provide a new strategy to overcome the obstacle of neutralizing antibodies in the clinical application of Reo.


Assuntos
Anticorpos Neutralizantes , Lipossomos , Neoplasias Ovarianas , Reoviridae , Feminino , Humanos , Neoplasias Ovarianas/imunologia , Anticorpos Neutralizantes/imunologia , Reoviridae/imunologia , Reoviridae/fisiologia , Linhagem Celular Tumoral , Terapia Viral Oncolítica/métodos , Apoptose , Animais , Cátions , Vírus Oncolíticos/imunologia , Camundongos
3.
Food Chem ; 459: 140381, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38991441

RESUMO

This study investigated the interaction between pea protein amyloid-like nanofibril and epigallocatechin gallate, constructed and characterized the novel pea protein nanofibrils-derived hydrogel mediated by epigallocatechin gallate, and researched the functionalities of the hydrogel. Epigallocatechin gallate remodeled the structure of pea protein nanofibrils, and a stable and strong hydrogel was formed at a relatively low protein concentration (4.5%). Additionally, the hydrogels exhibited various surface structures and hydrogel properties dependent on the mass ratio. Strongest gel strength (51 g) was attained at 0.25 epigallocatechin gallate/pea protein nanofibrils mass ratio. Whereas, the hydrogels exhibited the highest water holding capacity (87%) at 0.05 mass ratio. The primary driving forces in the formation and maintaining of the hydrogels were hydrophobic interactions and ionic bonds. Progressive rise of ß-sheet content of pea protein nanofibrils occurred increasing epigallocatechin gallate concentration. This hydrogel holds great potential for applications in food processing, targeted delivery of nutraceuticals and biomedicine.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38991991

RESUMO

INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

5.
Int J Biol Macromol ; : 133832, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002910

RESUMO

Salvia miltiorrhiza ethanol-extracted polysaccharide (SMEP) and thymopentin (TP5) have been proved with strong immunomodulatory activity, and T cells subsets play pivotal roles in the inhibition of solid tumors growth. In the present study, the structure of SMEP was further identified via methylation and nuclear magnetic resonance spectra, and the immunomodulatory activity in combination with TP5 was investigated via evaluating T cell subsets spatial distributions in tumor-bearing mice, finally the cellular status of solid tumor cells was analyzed. The results revealed that SMEP was a neutral heteropolysaccharide using (1 â†’ 4)-α-D-Glcp and (2 â†’ 1)-ß-D-Fruf as the main chain, along with branched chains of (1 â†’ 6)-α-D-Galp. The SMEP+TP5 treatments could effectively promote the differentiation and improve the specific recognition capacity of CD4+ T cells in tumor-bearing mice, thereby activate tumor-infiltrating CD8+ T cells to exert cytotoxic effects, finally promoting the tumor cells apoptosis via blocking cell cycle at G0/G1 phase, which might be relevant with suppression of Wnt/ß-catenin signaling pathway. These findings highlighted the potential of SMEP as an immunoadjuvant for patients bearing immune-deficiency related diseases, and provided data support for the functional researches of T cell subsets in tumor immunity.

6.
Foods ; 13(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998477

RESUMO

Silkworm (Bombyx mori) pupae are popular edible insects with high nutritional and therapeutic value. Currently, there is growing interest in the comprehensive application of silkworm pupae. In this study, peptides that exhibited anti-photoaging activity were obtained from silkworm pupae protein, aiming to investigate the protective effects and potential mechanisms of silkworm pupae peptides (SPPs) on skin photoaging. The results showed that SPPs were composed of 900 short peptides and could effectively alleviate skin photoaging progression. They significantly eliminated excessive production of ROS and MDA; meanwhile, they also renovated the antioxidant enzyme activities. The biomarkers related to collagen synthesis and degradation, including hydroxyproline, interstitial collagenase, and gelatinase, demonstrated that SPPs could suppress collagen degradation. Histopathological results showed that SPPs could reduce the inflammatory infiltrate and the thickness of the dermis and epidermis, as well as increase the collagen bundles and muscle fibers. The histopathological and biochemical results confirmed that SPPs could alleviate photoaging by inhibiting abnormal skin changes, reducing oxidative stress, and immune suppression. Overall, these data prove the protective effects of SPPs against the photoaging process, suggesting their potential as an active ingredient in skin photoaging prevention and therapy.

7.
J Agric Food Chem ; 72(31): 17549-17558, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39054671

RESUMO

ß-Lactoglobulin (ßLG) is a major allergen in bovine milk protein. This study was designed to investigate changes in ßLG structure, digestibility, and allergenicity induced by covalent binding modification with different contents of (-)-epigallocatechin 3-gallate (EGCG). The reaction of EGCG conjugation with ßLG reached saturation at a molar ratio of 1:60 ßLG:EGCG. Conjugation with EGCG altered the ßLG structure, decreased IgE-binding capacity, and increased digestibility in a dose-dependent manner. In vivo studies showed that covalent conjugation with EGCG can reduce ßLG-induced allergic symptoms with reducing levels of IgE, histamine, and mast cell protease-1 (mMCP-1) and the percentage of sensitized mast cells. Allergenicity was reduced more effectively in saturated ßLG-EGCG conjugates compared to semisaturated conjugates. Observed changes in IFN-γ, IL-4, IL-5, IL-10, and TGF-ß levels suggested that ßLG-EGCG conjugates were able to promote Th1/Th2 immune balance. These findings further our understanding of the relationship between the degree of polyphenol conjugation and the allergenicity of food allergens.


Assuntos
Alérgenos , Catequina , Imunoglobulina E , Lactoglobulinas , Lactoglobulinas/química , Lactoglobulinas/imunologia , Catequina/análogos & derivados , Catequina/química , Catequina/imunologia , Animais , Alérgenos/imunologia , Alérgenos/química , Bovinos , Imunoglobulina E/imunologia , Humanos , Camundongos , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/prevenção & controle , Camundongos Endogâmicos BALB C , Feminino , Interferon gama/imunologia , Interferon gama/metabolismo , Quimases/química , Quimases/imunologia , Quimases/metabolismo , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Interleucina-5/imunologia , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Mastócitos/imunologia , Mastócitos/efeitos dos fármacos
8.
Anal Bioanal Chem ; 416(19): 4275-4288, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38853180

RESUMO

Radix ginseng and Schisandra chinensis have been extensively documented in traditional Chinese medicine (TCM) for their potential efficacy in treating dementia. However, the precise mechanism of their therapeutic effects remains to be fully elucidated. In this study, air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and network pharmacology are used to investigate the pharmacodynamics and mechanism underlying the herbal combination consisting of Radix ginseng-Schisandra chinensis (RS) in a rodent model for Alzheimer's disease (AD). Brain histopathological findings suggested that RS attenuates hippocampal damage in AD mice, making this combination a potential AD treatment. Twenty-eight biomarkers were identified by spatial metabolomics analysis, which are intricately linked to neuroinflammation, neurotransmitter imbalance, energy deficiency, oxidative stress, and aberrant fatty acid metabolism in AD. The total extract of RS (TE) affected 22 of these biomarkers, with the small molecule components of RS (SN) significantly influencing 19 and the large molecule components of RS (PR) impacting 14. Nine small molecule components are likely to dominate the pharmacodynamics of RS. We constructed a target interaction network based on the corresponding bioactivities that revealed relationships amongst 11 key biomarkers, 8 active ingredients and 12 critical targets. This research illustrates the immense potential of spatial metabolomics and network pharmacology in the study of TCM, revealing the targets and mechanisms underlying herbal formulas.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Metabolômica , Farmacologia em Rede , Panax , Schisandra , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Metabolômica/métodos , Panax/química , Schisandra/química , Farmacologia em Rede/métodos , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Biomarcadores/metabolismo , Espectrometria de Massas por Ionização por Electrospray/métodos
9.
Kidney Int Rep ; 9(4): 1040-1046, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38765564

RESUMO

Introduction: The relationship of exostosin 1 and exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial. Methods: EXT1/EXT2 was performed by immunohistochemistry (IHC) in 283 consecutive patients with MLN. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients. The primary end points were adverse renal events, including death, dialysis, and renal transplantation. Results: Of the patients with MLN, 29.3% were positive for EXT1/EXT2. The prevalence of EXT1/2-positive MLN was significantly higher in pure class V MLN than those for mixed class V MLN (44.2% vs. 19.4%, P < 0.001). For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter (6 [interquartile range, IQR: 2-25] months vs. 12 [IQR: 3-49] months, P = 0.008 and 3 [IQR: 2-18] months vs. 6 [IQR: 2-23] months, P = 0.039) and they had significantly lower systemic lupus erythematosus Disease Activity Index (SLEDAI) scores (P = 0.015) and lower serum creatinine levels (P < 0.001), higher hemoglobin (P = 0.006) as well as lower blood pressure. The EXT1/EXT2-positive patients had significantly fewer chronicity features (glomerulosclerosis, P < 0.001; interstitial fibrosis, P = 0.006; and tubular atrophy, P = 0.002) and fewer activity indicators (endocapillary hypercellularity, P = 0.012; cellular crescents, P = 0.007; and fibrocellular crescents, P < 0.001) on renal biopsy. After a median follow-up of 65 (28-126) months, EXT1/EXT2-positive patients were less likely to experience adverse renal events (2.4% vs. 16.0%, P = 0.001). Conclusion: Compared with EXT1/EXT2-negative patients, the EXT1/EXT2-positive patients presented with lower disease activity and were less likely to experience adverse renal events in relationship with the chronicity index.

10.
Cutan Ocul Toxicol ; : 1-5, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781033

RESUMO

Introduction: This work was to explore the efficacy and safety of self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream in atopic dermatitis (AD) of spleen deficiency and dampness accumulation type. Material and method: 120 patients with this kind of atopic dermatitis were grouped: The Observation group (disease health education + basic treatment + mometasone furoate cream + self-made Decoction) and The Control group (disease health education + basic treatment + mometasone furoate cream), 60 cases in each group. The SCORAD score, serum IgE level, peripheral blood eosinophils, adverse events, recurrence rate, and total effective rate after treatment were observed.Result: Through treatment, SCORAD score of the observation group (29.96 ± 2.88) was lower as against controls (36.04 ± 3.12), p < 0.05. Through treatment, the peripheral blood eosinophil count in the observation group was (311.26 ± 50.19) 106/L, which was lower than (582.71 ± 54.75) 106/L in controls; the serum lgE of the observation group was (712.44 ± 93.32) IU/mL, which was lower than the controls (890.12 ± 81.25) IU/mL, p < 0.05. The Observation group (56/60, 93.33%) demonstrated superior total effective rate to the controls (34/60, 56.67%); The recurrence rate of the observation group was 4/60 (6.67%), which was lower than the controls 16/60 (26.67%), p < 0.05.Conclusion: Self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream to treat atopic dermatitis of spleen deficiency and dampness accumulation type has significant efficacy and good safety.

11.
Int J Biol Macromol ; 271(Pt 1): 132549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782331

RESUMO

Bovine serum albumin nanofibrils (BSNs) were fabricated under thermal treatment (85 °C) at acidic condition (pH 2.0) and the incubation time on the structural, and physicochemical characteristics were probed. The formation and development of BSNs have been detected and confirmed by Thioflavin T (ThT) fluorescence and circular dichroism (CD) measurements. The structural alterations of bovine serum albumin (BSA) have also been investigated using intrinsic fluorescence and Congo red (CGR) UV-vis spectroscopy. Atomic force microscopy (AFM) outcomes displayed the morphologies of BSNs at varied time, with a diameter of about 3 nm and a contour length of about 200 nm at 24 h. The apparent viscosities of BSNs at three different pH were in the following order: pH 3.0 > pH 5.0 > pH 7.0. Emulsifying and foaming properties of BSA were pronouncedly enhanced through fibrillation, which was highly correlated with the interfacial properties and structural characteristics. Highest EAI 54.2 m2/g was attained at 48 h and no pronounced alterations were observed for EAI at 24 h and 48 h. Maximum value of FC was obtained at 48 h for BSA. This study will provide some useful information in understanding the formation of BSNs and broaden their application in food systems as functional food ingredients.


Assuntos
Nanofibras , Soroalbumina Bovina , Soroalbumina Bovina/química , Animais , Nanofibras/química , Concentração de Íons de Hidrogênio , Bovinos , Emulsões/química , Fenômenos Químicos , Viscosidade
12.
J Transl Med ; 22(1): 274, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38475814

RESUMO

BACKGROUND: Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells. In response, this study aims to enhance CD19 CAR-NK cell efficacy and mitigate the risk of tumor recurrence due to target antigen escape by developing CD19 and CD20 (CD19/CD20) dual-targeted CAR-NK cells. METHODS: Initially, mRNA encoding anti-CD19 CARs (FMC63 scFv-CD8α-4-1BB-CD3ζ) and anti-CD20 CARs (LEU16 scFv-CD8α-4-1BB-CD3ζ) was constructed via in vitro transcription. Subsequently, CD19/CD20 dual-targeted CAR-NK cells were generated through simultaneous electrotransfection of CD19/CD20 CAR mRNA into umbilical cord blood-derived NK cells (UCB-NK). RESULTS: Following co-electroporation, the percentage of dual-CAR expression on NK cells was 86.4% ± 1.83%, as determined by flow cytometry. CAR expression was detectable at 8 h post-electric transfer, peaked at 24 h, and remained detectable at 96 h. CD19/CD20 dual-targeted CAR-NK cells exhibited increased specific cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines (BALL-1: CD19+CD20+, REH: CD19+CD20-, Jurkat: CD19-CD20-) compared to UCB-NK, CD19 CAR-NK, and CD20 CAR-NK cells. Moreover, CD19/CD20 dual-targeted CAR-NK cells released elevated levels of perforin, IFN-γ, and IL-15. Multiple activation markers such as CD69 and cytotoxic substances were highly expressed. CONCLUSIONS: The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Camundongos , Animais , Receptores de Antígenos Quiméricos/metabolismo , Antígenos CD19/genética , Antígenos CD19/metabolismo , Citotoxicidade Imunológica/genética , Linhagem Celular Tumoral , Células Matadoras Naturais , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , RNA Mensageiro/metabolismo
13.
Pancreatology ; 24(1): 130-136, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016861

RESUMO

BACKGROUND: Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) is a surgical method used to treat benign and low-grade malignant pancreatic head tumors. This study aimed to determine the protective effect of common bile duct in LDPPHR using indocyanine green (ICG) fluorescence imaging. METHODS: A retrospective analysis of 30 patients treated with LDPPHR at the Second Affiliated Hospital of Nanchang University between January 2015 and November 2022 was performed. Patients were divided into two groups based on ICG use: ICG and non-ICG. RESULTS: Thirty patients received LDPPHR, 11 males and 19 females, and the age was 50.50 (M (IQR)) years (range: 19-76 years). LDPPHR was successfully performed in 27 (90 %) patients, LPD was performed in 1 (3 %) patient, and laparotomy conversion was performed in 2 (7 %) patients. One patient (3 %) died 21 days after surgery. The incidence of intraoperative bile duct injury in the ICG group was lower than that in the non-ICG group (10 % vs 60 %, P = 0.009), and the operation time in the ICG group was shorter than that in the non-ICG group (311.9 ± 14.97 vs 338.05 ± 18.75 min, P < 0.05). Postoperative pancreatic fistula occurred in 16 patients (53 %), including 10 with biochemical leakage (62.5 %), four with grade B (25 %), and two with grade C (12.5 %). Postoperative bile leakage occurred in four patients (13 %). CONCLUSIONS: The ICG fluorescence imaging technology in LDPPHR helps protect the integrity of the common bile duct and reduce the occurrence of intraoperative bile duct injury, postoperative bile leakage, and bile duct stenosis.


Assuntos
Doenças dos Ductos Biliares , Laparoscopia , Masculino , Feminino , Humanos , Verde de Indocianina , Estudos Retrospectivos , Laparoscopia/métodos , Doenças dos Ductos Biliares/etiologia , Imagem Óptica/efeitos adversos , Imagem Óptica/métodos , Duodeno/diagnóstico por imagem , Duodeno/cirurgia
14.
Int J Mol Sci ; 24(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37958530

RESUMO

The high prevalence of kidney diseases and the low identification rate of drug nephrotoxicity in preclinical studies reinforce the need for representative yet feasible renal models. Although in vitro cell-based models utilizing renal proximal tubules are widely used for kidney research, many proximal tubule cell (PTC) lines have been indicated to be less sensitive to nephrotoxins, mainly due to altered expression of transporters under a two-dimensional culture (2D) environment. Here, we selected HK-2 cells to establish a simplified three-dimensional (3D) model using gelatin sponges as scaffolds. In addition to cell viability and morphology, we conducted a comprehensive transcriptome comparison and correlation analysis of 2D and 3D cultured HK-2 cells to native human PTCs. Our 3D model displayed stable and long-term growth with a tubule-like morphology and demonstrated a more comparable gene expression profile to native human PTCs compared to the 2D model. Many missing or low expressions of major genes involved in PTC transport and metabolic processes were restored, which is crucial for successful nephrotoxicity prediction. Consequently, we established a cost-effective yet more representative model for in vivo PTC studies and presented a comprehensive transcriptome analysis for the systematic characterization of PTC lines.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Gelatina , Humanos , Gelatina/farmacologia , Transcriptoma , Túbulos Renais Proximais/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Linhagem Celular , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Células Epiteliais/metabolismo , Células Cultivadas
15.
Int J Mol Sci ; 24(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37958581

RESUMO

The immune functions of the body are intricately intertwined with the onset and advancement of tumors, and immunotherapy mediated by bioactive compounds has exhibited initial effectiveness in overcoming chemotherapy resistance and inhibiting tumor growth. However, the comprehensive interpretation of the roles played by immunologic components in the process of combating tumors remains to be elucidated. In this study, the Codonopsis pilosula glucofructan (CPG) prepared in our previous research was employed as an immunopotentiator, and the impacts of CPG on both the humoral and cellular immunity of S180 tumor-bearing mice were investigated. Results showed that CPG administration of 100 mg/kg could effectively inhibit tumor growth in mice with an inhibitory ratio of 45.37% and significantly improve the expression of Interleukin-2 (IL-2), Interferon-γ (IFN-γ), and Tumor Necrosis Factor-α (TNF-α). Additionally, CPG clearly enhanced B-cell-mediated humoral immunity and immune-cell-mediated cellular immunity, and, finally, induced S180 cell apoptosis by arresting cells in the G0/G1 phase, which might result from the IL-17 signaling pathway. These data may help to improve comprehension surrounding the roles of humoral and cellular immunity in anti-tumor immune responses.


Assuntos
Codonopsis , Neoplasias , Animais , Camundongos , Interferon gama , Frutanos , Neoplasias/tratamento farmacológico , Imunidade Celular
16.
Expert Rev Vaccines ; 22(1): 956-963, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37855091

RESUMO

BACKGROUND: As pregnant women are excluded from clinical trials of inactivated SARS-CoV-2 vaccines, it is important to assess the immune response in women receiving the vaccination while unknowingly pregnant. METHODS: In a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18-45 years. Serum antibody levels induced by inactivated vaccines were determined. Adverse events were collected by self-reported survey after vaccination. Logistic regression model and restricted cubic spline model were used to investigate the association of factors with antibody positivity. RESULTS: As the doses of the vaccine increase, neutralizing antibody (NAb) positivity was 98.3%, 39.5%, and 9.5% in pregnant women, respectively. The dose of vaccine and duration since vaccination were associated with NAb positivity. The OR of two and three doses of vaccines were 7.20 and 458.33 (P < 0.05). NAb levels and duration since vaccination showed a linear relationship in pregnant women vaccinated two doses, with a decrease to a near seropositivity threshold at 22 weeks. Adverse events were mainly mild or moderate after vaccinated during pregnancy, with no increase in incidence compared with whom vaccinated during pre-pregnancy. CONCLUSIONS: The use of inactivated vaccines during pregnancy induced favorable immune persistence, and the incidence of adverse events did not increase.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Gravidez , Feminino , Humanos , Vacinas contra COVID-19/efeitos adversos , Estudos Transversais , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação/efeitos adversos , Anticorpos Neutralizantes , Vacinas de Produtos Inativados/efeitos adversos , Imunidade , Anticorpos Antivirais
17.
Surg Endosc ; 37(12): 9116-9124, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37803187

RESUMO

BACKGROUND: This study aimed to investigate the safety and efficacy of laparoscopic anatomical left hemihepatectomy guided by the middle hepatic vein (MHV) for the treatment of patients with hepatolithiasis who had a history of upper abdominal surgery. METHODS: Retrospective data analysis was performed on patients who underwent laparoscopic left hepatectomy for hepatolithiasis and with previous upper abdominal surgery at the Second Affiliated Hospital of Nanchang University from January 2018 to April 2022. According to the different surgical approaches, patients were divided into laparoscopic anatomical left hepatectomy guided by the MHV group (MHV-AH group) and laparoscopic traditional anatomical left hepatectomy not guided by the MHV group (non-MHV-AH group). RESULTS: This study included 81 patients, with 37 and 44 patients in the MHV-AH and non-MHV-AH groups, respectively. There was no significant difference in the basic information between the two groups. Five cases were converted to laparotomy, and the remaining were successfully completed under laparoscopy. Compared to the non-MHV-AH group, the MHV-AH group had a slightly longer operation time (319.30 min vs 273.93 min, P = 0.032), lower bile leakage rate (5.4% vs 20.5%, P = 0.047), stone residual rate (2.7% vs 20.5%, P = 0.015), stone recurrence rate (5.4% vs 22.7%, P = 0.028), and cholangitis recurrence rate (2.7% vs 22.7%, P = 0.008).There were no significant differences in the results of other observation indices between the groups. CONCLUSIONS: Laparoscopic anatomical left hepatectomy guided by the MHV is safe and effective in the treatment of left hepatolithiasis with a history of upper abdominal surgery. It does not increase intraoperative bleeding and reduces the risk of postoperative bile leakage, residual stones, stone recurrence, and cholangitis recurrence.


Assuntos
Cálculos , Colangite , Laparoscopia , Litíase , Hepatopatias , Humanos , Hepatectomia/métodos , Hepatopatias/cirurgia , Litíase/cirurgia , Estudos Retrospectivos , Veias Hepáticas , Resultado do Tratamento , Cálculos/cirurgia , Laparoscopia/métodos , Colangite/etiologia
18.
Molecules ; 28(18)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37764221

RESUMO

Thymopentin (TP5) has exhibited strong antitumor and immunomodulatory effects in vivo. However, the polypeptide is rapidly degraded by protease and aminopeptidase within a minute at the N-terminal of TP5, resulting in severe limitations for further practical applications. In this study, the protective effects of water-soluble alginic acid (WSAA) on the N-terminal of TP5 were investigated by establishing an H22 tumor-bearing mice model and determining thymus, spleen, and liver indices, immune cells activities, TNF-α, IFN-γ, IL-2, and IL-4 levels, and cell cycle distributions. The results demonstrated that WSAA+TP5 groups exhibited the obvious advantages of the individual treatments and showed superior antitumor effects on H22 tumor-bearing mice by effectively protecting the immune organs, activating CD4+ T cells and CD19+ B cells, and promoting immune-related cytokines secretions, finally resulting in the high apoptotic rates of H22 cells through arresting them in S phase. These data suggest that WSAA could effectively protect the N-terminal of TP5, thereby improving its antitumor and immunoregulatory activities, which indicates that WSAA has the potential to be applied in patients bearing cancer or immune deficiency diseases as a novel immunologic adjuvant.


Assuntos
Ácido Algínico , Timopentina , Humanos , Camundongos , Animais , Timopentina/farmacologia , Timopentina/metabolismo , Adjuvantes Imunológicos/farmacologia , Linfócitos T/metabolismo , Timo/metabolismo
19.
Nutrients ; 15(17)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37686775

RESUMO

Milk Oligosaccharides (MOS), a group of complex carbohydrates found in human and bovine milk, have emerged as potential modulators of optimal brain development for early life. This review provides a comprehensive investigation of the impact of milk oligosaccharides on brain and neurocognitive development of early life by synthesizing current literature from preclinical models and human observational studies. The literature search was conducted in the PubMed search engine, and the inclusion eligibility was evaluated by three reviewers. Overall, we identified 26 articles for analysis. While the literature supports the crucial roles of fucosylated and sialylated milk oligosaccharides in learning, memory, executive functioning, and brain structural development, limitations were identified. In preclinical models, the supplementation of only the most abundant MOS might overlook the complexity of naturally occurring MOS compositions. Similarly, accurately quantifying MOS intake in human studies is challenging due to potential confounding effects such as formula feeding. Mechanistically, MOS is thought to impact neurodevelopment through modulation of the microbiota and enhancement of neuronal signaling. However, further advancement in our understanding necessitates clinical randomized-controlled trials to elucidate the specific mechanisms and long-term implications of milk oligosaccharides exposure. Understanding the interplay between milk oligosaccharides and cognition may contribute to early nutrition strategies for optimal cognitive outcomes in children.


Assuntos
Encéfalo , Leite , Criança , Humanos , Animais , Oligossacarídeos/farmacologia , Cognição , Função Executiva
20.
Artigo em Inglês | MEDLINE | ID: mdl-37770137

RESUMO

The effect of pH on DNA integrity was assessed using a three-step approach. The comet assay was used on a whole genome level, with three different protocols: neutral (no alkaline unwinding), flash (pH 12.5 with 2.5 min unwinding), and the conventional alkaline protocol (pH>13 with 40 min unwinding). Real-time quantitative PCR (RT-qPCR) was then used to study the isolated DNA, revealing that gene amplification decreased with increasing pH, indicating DNA degradation. Specially designed molecular beacons were used to examine DNA at the molecular level, with or without alkali-labile site (ALS) insertions. At pH 12.5, fluorescence in the hairpins with ALS started to increase after 30 min, while at pH> 13, this increase was already observed after 5 min, indicating a significant increase in DNA strand breaks. Liquid chromatography analysis was also used, demonstrating that the hairpins remained intact up to pH 10, even after 1 h exposure, whereas, at pH 12.5, partial conversion into strand breaks occurred after 30 min. At pH> 13, the hairpins were almost completely degraded after 30 min. The flash protocol effectively detects DNA single- and double-strand breaks and identified these damages after 2.5 min of alkaline treatment at pH 12.5. When the hairpins were exposed to pH 12.5 for 60 min, ALS were converted to strand breaks, demonstrating the sensitivity of this approach to detect changes in DNA structure. These findings indicate that pH poses a substantial risk to DNA integrity, leading to significantly higher background levels of DNA damage compared to conditions closer to neutrality. Our study demonstrates the importance of understanding the influence of pH on DNA stability and provides insights into risks associated with alkaline environments, especially at pH> 13.


Assuntos
Ensaio Cometa , Humanos , Ensaio Cometa/métodos , DNA , Dano ao DNA , Reparo do DNA , Concentração de Íons de Hidrogênio
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