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1.
Leuk Lymphoma ; : 1-9, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38708448

RESUMEN

The survival rate of non-Hodgkin lymphoma (NHL) has steadily improved. However, osteoporosis introduced by treatment is prevalent and associated with increased mortality and disability for patients with NHL. We aimed to investigate factors impacting bone mineral density (BMD) reduction and osteoporosis, and the trend of BMD after chemotherapy. Overall, 97 newly diagnosed patients with follicular lymphoma (FL) were retrospectively enrolled. CT attenuation values were measured to assess BMD levels. Although 73.2% of patients received calcium and vitamin D supplements, 44.3% showed significant BMD reduction, and baseline BMD and hemoglobin levels were the risk factors. 26.6% of patients newly developed osteoporosis post-chemotherapy where age and cumulative dose of glucocorticoid were risk factors. The results of 20 patients with consecutive follow-up showed that BMD continued to decline for 6 months post-chemotherapy and did not return to baseline values. Therefore, BMD evaluation and more positive anti-resorption treatments should be administered for high-risk patients.

2.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38612877

RESUMEN

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.


Asunto(s)
Hedera , Ácido Oleanólico/análogos & derivados , Saponinas , Glicosiltransferasas/genética
3.
IEEE Trans Med Imaging ; PP2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652607

RESUMEN

Proximal femoral fracture segmentation in computed tomography (CT) is essential in the preoperative planning of orthopedic surgeons. Recently, numerous deep learning-based approaches have been proposed for segmenting various structures within CT scans. Nevertheless, distinguishing various attributes between fracture fragments and soft tissue regions in CT scans frequently poses challenges, which have received comparatively limited research attention. Besides, the cornerstone of contemporary deep learning methodologies is the availability of annotated data, while detailed CT annotations remain scarce. To address the challenge, we propose a novel weakly-supervised framework, namely Rough Turbo Net (RT-Net), for the segmentation of proximal femoral fractures. We emphasize the utilization of human resources to produce rough annotations on a substantial scale, as opposed to relying on limited fine-grained annotations that demand a substantial time to create. In RT-Net, rough annotations pose fractured-region constraints, which have demonstrated significant efficacy in enhancing the accuracy of the network. Conversely, the fine annotations can provide more details for recognizing edges and soft tissues. Besides, we design a spatial adaptive attention module (SAAM) that adapts to the spatial distribution of the fracture regions and align feature in each decoder. Moreover, we propose a fine-edge loss which is applied through an edge discrimination network to penalize the absence or imprecision edge features. Extensive quantitative and qualitative experiments demonstrate the superiority of RT-Net to state-of-the-art approaches. Furthermore, additional experiments show that RT-Net has the capability to produce pseudo labels for raw CT images that can further improve fracture segmentation performance and has the potential to improve segmentation performance on public datasets. The code is available at: https://github.com/zyairelu/RT-Net.

5.
Int Immunopharmacol ; 133: 112066, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38615377

RESUMEN

Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.


Asunto(s)
Apoptosis , Proliferación Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia , Serina-Treonina Quinasas TOR , Valeriana , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Humanos , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Valeriana/química , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Ratones Desnudos , Ratones Endogámicos BALB C , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico
6.
Zhongguo Zhong Yao Za Zhi ; 49(4): 942-950, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621901

RESUMEN

Scorpio, a commonly used animal medicine in China, is derived from Buthus martensii as recorded in the Chinese Pharmacopoeia. China harbors rich species of Scorpionida and adulterants exist in the raw medicinal material and deep-processed products of Scorpio. The microscopic characteristics of the deep-processed products may be incomplete or lost during processing, which makes the identification difficult. In this study, the maximum likelihood(ML) tree was constructed based on the morphology and cytochrome C oxidase subunit I(COⅠ) to identify the species of Scorpio products. The results showed that the main adulterant of Scorpio was Lychas mucronatus. According to the specific SNP sites in the COⅠ sequence of B. martensii, the stable primers were designed for the identification of the medicinal material and formula granules of Scorpio. The polymerase chain reaction(PCR) at the annealing temperature of 61 ℃ and 30 cycles produced bright specific bands at about 150 bp for both B. martensii and its formula particles and no band for adulterants. The adaptability of the method was investigated, which showed that the bands at about 150 bp were produced for Scorpio medicinal material, lyophilized powder, and formula granules, and commercially available formula granules. The results showed that the established method could be used to identify the adulterants of Scorpio and its formula granules, which could help to improve the quality control system and ensure the safe clinical application of Scorpio formula granules.


Asunto(s)
Animales Ponzoñosos , Medicamentos Herbarios Chinos , Escorpiones , Animales , Reacción en Cadena de la Polimerasa/métodos
7.
Biotechnol J ; 19(4): e2400078, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38651251

RESUMEN

Due to their high-quality characteristics, Chinese hamster ovary (CHO) cells have become the most widely used and reliable host cells for the production of recombinant therapeutic proteins in the biomedical field. Previous studies have shown that the m6A reader YTHDF3, which contains the YTH domain, can affect a variety of biological processes by regulating the translation and stability of target mRNAs. This study investigates the effect of YTHDF3 on transgenic CHO cells. The results indicate that stable overexpression of YTHDF3 significantly enhances recombinant protein expression without affecting host cell growth. Transcriptome sequencing indicated that several genes, including translation initiation factor, translation extension factor, and ribosome assembly factor, were upregulated in CHO cells overexpressing YTHDF3. In addition, cycloheximide experiments confirmed that YTHDF3 enhanced transgene expression by promoting translation in CHO cells. In conclusion, the findings in this study provide a novel approach for mammalian cell engineering to increase protein productivity by regulating m6A.


Asunto(s)
Cricetulus , Biosíntesis de Proteínas , Proteínas de Unión al ARN , Proteínas Recombinantes , Animales , Células CHO , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Biosíntesis de Proteínas/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Cricetinae
8.
Mar Drugs ; 22(4)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38667762

RESUMEN

Four undescribed sesquiterpenoids, lemneolemnanes A-D (1-4), have been isolated from the marine soft coral Lemnalia sp. The absolute configurations of the stereogenic carbons of 1-4 were determined by single-crystal X-ray crystallographic analysis. Compounds 1 and 2 are epimers at C-3 and have an unusual skeleton with a formyl group on C-6. Compound 3 possesses an uncommonly rearranged carbon skeleton, while 4 has a 6/5/5 tricyclic system. Compound 1 showed significant anti-Alzheimer's disease (AD) activity in a humanized Caenorhabditis elegans AD pathological model.


Asunto(s)
Antozoos , Caenorhabditis elegans , Sesquiterpenos , Animales , Antozoos/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Caenorhabditis elegans/efectos de los fármacos , Cristalografía por Rayos X , Enfermedad de Alzheimer/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Estructura Molecular
9.
Artículo en Inglés | MEDLINE | ID: mdl-38683722

RESUMEN

The fund investment industry heavily relies on the expertise of fund managers, who bear the responsibility of managing portfolios on behalf of clients. With their investment knowledge and professional skills, fund managers gain a competitive advantage over the average investor in the market. Consequently, investors prefer entrusting their investments to fund managers rather than directly investing in funds. For these investors, the primary concern is selecting a suitable fund manager. While previous studies have employed quantitative or qualitative methods to analyze various aspects of fund managers, such as performance metrics, personal characteristics, and performance persistence, they often face challenges when dealing with a large candidate space. Moreover, distinguishing whether a fund manager's performance stems from skill or luck poses a challenge, making it difficult to align with investors' preferences in the selection process. To address these challenges, this study characterizes the requirements of investors in selecting suitable fund managers and proposes an interactive visual analytics system called FMLens. This system streamlines the fund manager selection process, allowing investors to efficiently assess and deconstruct fund managers' investment styles and abilities across multiple dimensions. Additionally, the system empowers investors to scrutinize and compare fund managers' performances. The effectiveness of the approach is demonstrated through two case studies and a qualitative user study. Feedback from domain experts indicates that the system excels in analyzing fund managers from diverse perspectives, enhancing the efficiency of fund manager evaluation and selection.

10.
Curr Med Sci ; 44(2): 291-297, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38517674

RESUMEN

Postoperative cognitive dysfunction (POCD) remains a major issue that worsens the prognosis of elderly surgery patients. This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients, aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols, ultimately reducing the incidence of POCD in elderly surgery patients.


Asunto(s)
Anestesia , Disfunción Cognitiva , Complicaciones Cognitivas Postoperatorias , Humanos , Anciano , Complicaciones Cognitivas Postoperatorias/inducido químicamente , Complicaciones Cognitivas Postoperatorias/epidemiología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Anestesia/efectos adversos , Anestésicos Intravenosos
11.
Fitoterapia ; 175: 105881, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38438054

RESUMEN

Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.

12.
Int. j. clin. health psychol. (Internet) ; 24(1): [100432], Ene-Mar, 2024. tab, ilus, graf
Artículo en Inglés | IBECS | ID: ibc-230372

RESUMEN

Background: Emerging evidence increasingly suggests that poor sleep quality is associated with depressive symptoms. The hippocampus might play a crucial role in the interplay between sleep disturbance and depressive symptomatology, e.g., hippocampal atrophy is typically seen in both insomnia disorder and depression. Thus, examining the role of hippocampal volume in the interplay between poor sleep quality and depressive symptoms in large healthy populations is vital. Methods: We investigated the association between self-reported sleep quality, depressive symptoms, and hippocampal total and subfields’ volumes in 1603 healthy young adults from the Behavioral Brain Research Project. Mediation analysis explored the mediating role of hippocampal volumes between sleep quality and depressive symptoms. Results: Self-reported sleep quality and depressive symptoms were positively correlated. In addition, it negatively related to three hippocampal subfields but not total hippocampal volume. In particular, hippocampal subfield DG and CA4 volumes mediated the interrelationship between poor sleep quality and depressive symptoms. Conclusions: Our findings improved the current understanding of the relationship between sleep disturbance, depressive symptomatology, and hippocampal subfields in healthy populations. Considering the crucial role of DG in hippocampal neurogenesis, our results suggest that poor sleep quality may contribute to depression through a reduction of DG volume leading to impaired neurogenesis which is crucial for the regulation of mood.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Depresión , Giro Parahipocampal , Giro Dentado , Psicología Clínica
13.
Heliyon ; 10(5): e26901, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38468921

RESUMEN

The human cytomegalovirus major immediate early gene (CMV) promoter is currently the most preferred promoter for recombinant therapeutic proteins (RTPs) production in CHO cells. To enhance the production of RTPs, five synthetic enhancers including multiple transcription factor regulatory elements (TFREs) were evaluated to enhance recombinant protein level in transient and stably transfected CHO cells. Compared with the control, four elements can enhance the report genes expression under both two transfected states. Further, the function of these four enhancers on human serum albumin (HSA) were investigated. We found that the transient expression can increase by up to 1.5 times, and the stably expression can maximum increase by up to 2.14 times. The enhancement of transgene expression was caused by the boost of their corresponding mRNA levels. Transcriptomics analysis was performed and found that transcriptional activation and cell cycle regulation genes were involved. In conclusion, optimization of enhancers in the CMV promoter could increase the production yield of transgene in transfected CHO cells, which has significance for developing high-yield CHO cell expression system.

14.
Poult Sci ; 103(4): 103413, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38442558

RESUMEN

Photoperiod is an important environmental factor that influences seasonal reproduction behavior in birds. Birds translate photoperiodic information into neuroendocrine signals through deep brain photoreceptors (DBPs). OPN5 has been considered candidate DBPs involved in regulating seasonal reproduction in birds. We found that OPN5 could mediate light to regulate the follicle development in ducks. In this study, we further verified the effect of OPN5 on follicular development in Shan Partridge ducks by immunizing against the extracellular domain (ECD) of OPN5. We investigated the specific regulatory mechanism of photoperiod mediated by OPN5 on the reproductive activity of ducks. The trial randomly divided 120 Shan Partridge ducks into 3 groups with different treatments: the immunization of OPN5 group was done at d0, d15, d30, and d40 with 1 mL of vaccine containing OPN5 protein (thus containing 1, 1, 0.5, and 0.5 mg of OPN5-KLH protein), and the control group (CS and CL groups) was injected at the same time with the same dose of OPN5-uncontained blank vaccine. The group of CS (900 lux), OPN5 (600 lux), and CL (600 lux) lasted for 40 d in 12 L:12 D photoperiods, respectively. Then, the groups of CS, OPN5, and CL subsequently received 12 L:12 D, 12 L:12 D, and 17 L:7 D light treatments for 33 d, respectively. The ducks were caged in 3 constant rooms with the same feeding conditions for each group, free water, and limited feeding (150 g per duck each day). Duck serum and tissue samples were collected at d 40, d 62, and d 73 (n = 12). It was found that before prolonged light, the group of immunization (group OPN5) and the group of strong light intensity (group CS) were higher than the group of CL in egg production. Subsequent to prolonged light, the group CL in egg production rose about the same as the group immunization, while the strong light group (group CS) was lower. Group OPN5 increased the ovarian index of ducks, and both the immunization of group OPN5 and group CL (extended light) increased the thickness of the granular layer and promoted the secretion of E2, P4, LH, and PRL hormones. Compared with group CS, group CL and OPN5 increased the mRNA level and protein expression of OPN5 in the hypothalamus on d 62 and d 73 (P < 0.05). The gene or protein expression patterns of GnRH, TRH, TSHß, DIO2, THRß, VIP, and PRL were positively correlated with OPN5, whereas the gene expression patterns of GnIH and DIO3 were negatively correlated with OPN5. The results showed that immunization against OPN5 could activate the corresponding transmembrane receptors to promote the expression of OPN5, up-regulate the expression of TSHß and DIO2, and then regulate the HPG axis-related genes to facilitate the follicular development of Shan Partridge ducks. In addition, in this experiment, prolonging the photoperiod or enhancing the light intensity could also enhance follicle development, but the effect was not as significant as immunizing against OPN5. Our results will offer beneficial data and more supportive shreds of evidence in favor of elucidating the role of OPN5 in relation to photoperiods and reproduction.


Asunto(s)
Fotoperiodo , Vacunas , Animales , Patos/fisiología , Pollos , Reproducción , Inmunización/veterinaria
15.
Acta Pharmacol Sin ; 45(5): 1044-1059, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38326625

RESUMEN

The development of targeted chemotherapeutic agents against colorectal cancer (CRC), one of the most common cancers with a high mortality rate, is in a constant need. Nannocystins are a family of myxobacterial secondary metabolites featuring a 21-membered depsipeptide ring. The in vitro anti-CRC activity of natural and synthetic nannocystins was well documented, but little is known about their in vivo efficacy and if positive, the underlying mechanism of action. In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dependently inhibited the colony formation and migration of CRC cell lines. Moreover, compound 4 induced cell cycle arrest at sub-G1 phase, apoptosis and cellular senescence in CRC cell lines. In three patient-derived CRC organoids, compound 4 inhibited the PDO with IC values of 3.68, 28.93 and 11.81 nM, respectively. In a patient-derived xenograft mouse model, injection of compound 4 (4, 8 mg/kg, i.p.) every other day for 12 times dose-dependently inhibited the tumor growth without significant change in body weight. We conducted RNA-sequencing, molecular docking and cellular thermal shift assay to elucidate the anti-CRC mechanisms of compound 4, and revealed that it exerted its anti-CRC effect at least in part by targeting AKT1.


Asunto(s)
Antineoplásicos , Proliferación Celular , Neoplasias Colorrectales , Depsipéptidos , Compuestos Macrocíclicos , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Depsipéptidos/farmacología , Depsipéptidos/uso terapéutico , Depsipéptidos/química , Depsipéptidos/síntesis química , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Oncol Lett ; 27(3): 99, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38298425

RESUMEN

Visceral adipose tissue and skeletal muscle mass are associated with carcinogenesis and clinical outcomes in patients with cancer. The aim of the present study was to determine the influence of body composition parameters on postoperative survival in patients with gastric cancer. Demographic data and systemic inflammatory response data were obtained from patients with gastric cancer undergoing radical gastrectomy. The patient's skeletal muscle and visceral fat were assessed using computed tomography, and the corresponding skeletal muscle index (SMI) and visceral fat index (VFI) were calculated. Univariate and multivariate analyses were then performed. Of the 342 patients from whom information was collected, 125 of these patients eventually succumbed to the disease. A total of 271 (79.24%) of the patients were male and 71 (20.76%) were female. Regarding the entire cohort, the mean age was 64 years [interquartile range (IQR), 56-74 years], while the mean body mass index collected was 21.53 (IQR, 19.27-24.22). The median SMI and VFI of the patients were 47.73 (IQR, 41.67-55.51) and 41.28 (IQR, 36.62-45.36), respectively. It was concluded that a low SMI and VFI were associated with worse survival outcomes. However, the neutrophil-to-lymphocyte ratio and perioperative blood transfusion were not significantly associated with overall survival (OS). Among the indicators assessed, a low VFI was an independent risk factor associated with the worst OS time (hazard ratio 1.59; confidence interval, 1.03-2.45; P=0.038). Finally, a prognostic nomogram was constructed which included the VFI to assist clinicians in making more informed decisions. In conclusion, after data collection and analysis, it was found that there was a significant correlation between a low VFI and a shorter OS time in patients with gastric cancer following gastrectomy, suggesting that VFI may be a promising therapeutic target for postoperative interventions to improve patient survival further.

17.
Ecotoxicol Environ Saf ; 273: 116149, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38412632

RESUMEN

It is still a serious public health issue that chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka poses challenges in identification, prevention, and treatment. What environmental factors in drinking water cause kidney damage remains unclear. This study aimed to investigate the risks of various environmental factors that may induce CKDu, including water hardness, fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM). The research focused on comprehensive metabolome analysis, and correlation with transcriptomic and gut microbiota changes. Results revealed that chronic exposure led to kidney damage and pancreatic toxicity in adult zebrafish. Metabolomics profiling showed significant alterations in biochemical processes, with enriched metabolic pathways of oxidative phosphorylation, folate biosynthesis, arachidonic acid metabolism, FoxO signaling pathway, lysosome, pyruvate metabolism, and purine metabolism. The network analysis revealed significant changes in metabolites associated with renal function and diseases, including 20-Hydroxy-LTE4, PS(18:0/22:2(13Z,16Z)), Neuromedin N, 20-Oxo-Leukotriene E4, and phenol sulfate, which are involved in the fatty acyls and glycerophospholipids class. These metabolites were closely associated with the disrupted gut bacteria of g_ZOR0006, g_Pseudomonas, g_Tsukamurella, g_Cetobacterium, g_Flavobacterium, which belonged to dominant phyla of Firmicutes and Proteobacteria, etc., and differentially expressed genes (DEGs) such as egln3, ca2, jun, slc2a1b, and gls2b in zebrafish. Exploratory omics analyses revealed the shared significantly changed pathways in transcriptome and metabolome like calcium signaling and necroptosis, suggesting potential biomarkers for assessing kidney disease.


Asunto(s)
Agua Potable , Insuficiencia Renal Crónica , Animales , Agua Potable/análisis , Pez Cebra , Sri Lanka , Insuficiencia Renal Crónica/etiología , Metaboloma
18.
Front Psychol ; 15: 1321441, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414879

RESUMEN

Objective: Frequent teacher turnover may damage the development of teachers and the regular operation of kindergartens. This original research presented kindergarten teachers' first, second, and third turnover rates and occurrence times. This research analyzed the relationship between socio-demographic variables and the varying frequency of kindergarten teacher turnover. These data were used to investigate the characteristics of first, second, and third kindergarten turnover. This research evaluated kindergarten teachers' occupational ambition, emotional attachment, and self-efficacy. Likewise, this research also analyzed the social context, organizational support, management mechanism, reward, and occupational stress of kindergarten. These data were used to determine the key factors affecting kindergarten teachers' turnover. Methods: This research recruited 1,118 kindergarten teachers (mean age = 31.67, sd = 5.02; 3.85% male, 96.14% female) from China. Based on the existing scales, this research developed the Questionnaire of Kindergarten Teachers' Turnover and Influencing Factors for the survey. Kindergarten teachers reported basic information and the impact factors of their first, second, and third turnover through online questionnaires. The Chi-square test was used to analyze the correlation between socio-demographic variables and different frequencies of kindergarten teacher turnover. The binary logistic regression explored the eight factors affecting kindergarten teachers' first, second, and third turnover. Results: The results showed that 43.65% of kindergarten teachers had resigned. In detail, 25.60% of kindergarten teachers resigned once, 10.64% of kindergarten teachers resigned twice, and 8.41% of kindergarten teachers resigned thrice. Gender and marital status were significantly correlated with the three frequencies of kindergarten teacher turnover. Occupational stress, reward, management mechanisms, and ambition consistently affected kindergarten teachers' first, second, and third turnover. Conclusion: The relevant management departments should pay attention to the high turnover rate of kindergarten teachers and put forward more strategies to improve their stability. Women and married can be favored in the recruitment of kindergarten teachers. It is crucial to reduce pressure and improve rewards for kindergarten teachers. Also, kindergartens should provide the space to display teachers' talents and improve management mechanisms. These results provide empirical support for proposing effective policies to promote the stability of kindergarten teachers' construction.

20.
Nutrients ; 16(1)2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38201981

RESUMEN

Clostridium butyricum (CB) and Phellinus igniarius (PI) have anti-inflammatory, immune regulation, anti-tumor, and other functions. This study aimed to explore the therapeutic effect of CB and mycelium of PI (MPI) alone and in combination on colitis mice induced by dextran sodium sulfate (DSS). Mice were randomly assigned to five groups: (1) control (CTRL), (2) DSS, (3) CB, (4) MPI, and (5) CB + MPI (CON). The weight of the mice was recorded daily during the experiment, and the length of the colon was measured on the last day of the experiment. The colons were collected for hematoxylin and eosin staining, colon contents were collected for intestinal flora analysis, and serum was collected for metabolite analysis. The results showed that compared with the DSS group, CB, MPI, and CON treatments inhibited the weight loss and colon length shortening caused by DSS, significantly increased the concentrations of interleukin (IL)-4, IL-10, and superoxide dismutase, and significantly decreased the concentrations of IL-6, tumor necrosis factor-α, and myeloperoxidase. Gene sequence analysis of 16S rRNA showed that CB, MPI, and CON treatments changed the composition and structure of intestinal microorganisms. Metabolome results showed that CB, MPI, and CON treatments changed serum metabolites in DSS-treated mice, including dodecenoylcarnitine, L-urobilinogen, and citric acid. In conclusion, CB, MPI, and CON treatments alleviated DSS-induced colitis in mice by regulating intestinal flora and metabolites, with the CON group having the best effect.


Asunto(s)
Clostridium butyricum , Colitis , Microbioma Gastrointestinal , Phellinus , Animales , Ratones , ARN Ribosómico 16S/genética , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Micelio
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