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1.
Pak J Med Sci ; 40(6): 1105-1110, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952537

RESUMEN

Objective: To assess the effect of Traditional Chinese Medicine (TCM) nutrition treatment (Bushenhuoxue nutritional decoction) in overweight patients with polycystic ovary syndrome (PCOS). Methods: Retrospective analysis of 96 overweight patients with PCOS who received treatment in our hospital from October 2020 to June 2022 was done. Among them, 46 patients received routine drug treatment and daily dietary intervention (control group), while 50 patients received additional TCM nutrition support in addition to routine treatment (observation group). Glucose and lipid metabolism indicators and hormone levels were compared between the two groups before and after the treatment. Ovulation rate, pregnancy rate, and adverse reactions were compared between both groups one year after the treatment. Results: After treatment, the improvement of glucose and lipid metabolism indicators and hormone levels in the observation group was significantly better than in the control group (P<0.05). After treatment, the TCM syndrome scores of the two groups were lower than that before treatment (P < 0.001), and the TCM syndrome scores of the observation group was lower than that of the control group (P < 0.001).Ovulation and pregnancy rates were significantly higher in the observation group compared to the control group at 1-year follow up (P<0.05), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (P<0.05). Conclusions: Combined with conventional drug treatment, TCM nutrition treatment can significantly improve glucose and lipid metabolism, hormone levels, and TCM syndrome of overweight PCOS patients, increase the ovulation and pregnancy rates, and reduce potential adverse reactions.

2.
Arch Pharm (Weinheim) ; : e2400192, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961537

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown etiology. Currently, drugs used to treat IPF in clinical practice exhibit severe side effects and limitations. To address these issues, this paper discusses the therapeutic effects of preclinical targeted drugs (such as STAT3 and TGF-ß/Smad pathway inhibitors, chitinase inhibitors, PI3K and phosphodiesterase inhibitors, etc.) and natural products on IPF. Through a summary of current research progress, it is found that natural products possess multitarget effects, stable therapeutic efficacy, low side effects, and nondrug dependence. Furthermore, we discuss the significant prospects of natural product molecules in combating fibrosis by influencing the immune system, expecting that current analytical data will aid in the development of new drugs or the investigation of active ingredients in natural products for potential IPF treatments in the future.

3.
ACS Med Chem Lett ; 15(6): 864-872, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38894924

RESUMEN

We were attracted to the therapeutic potential of inhibiting Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING E3 ligase that plays a critical role in regulating the activation of T cells. However, given that only protein-protein interactions were involved, it was unclear whether inhibition by a small molecule would be a viable approach. After screening an ∼6 billion member DNA-encoded library (DEL) using activated Cbl-b, we identified compound 1 as a hit for which the cis-isomer (2) was confirmed by biochemical and surface plasmon resonance (SPR) assays. Our hit optimization effort was greatly accelerated when we obtained a cocrystal structure of 2 with Cbl-b, which demonstrated induced binding at the substrate binding site, namely, the Src homology-2 (SH2) domain. This was quite noteworthy given that there are few reports of small molecule inhibitors that bind to SH2 domains and block protein-protein interactions. Structure- and property-guided optimization led to compound 27, which demonstrated measurable cell activity, albeit only at high concentrations.

4.
Adv Sci (Weinh) ; : e2403098, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898726

RESUMEN

Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross-contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy-modified carbon nitride nanosheets (g-C3N4-VC Ns) coated on the non-woven fabrics of the out layer of the mask, offering effective and long-term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy-disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron-hole pairs, thus promoting the electron-hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as-prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self-protection.

5.
J Cell Mol Med ; 28(12): e18373, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38894657

RESUMEN

Gastric cancer (GC) remains a prominent malignancy that poses a significant threat to human well-being worldwide. Despite advancements in chemotherapy and immunotherapy, which have effectively augmented patient survival rates, the mortality rate associated with GC remains distressingly high. This can be attributed to the elevated proliferation and invasive nature exhibited by GC. Our current understanding of the drivers behind GC cell proliferation remains limited. Hence, in order to reveal the molecular biological mechanism behind the swift advancement of GC, we employed single-cell RNA-sequencing (scRNA-seq) to characterize the tumour microenvironment in this study. The scRNA-seq data of 27 patients were acquired from the Gene Expression Omnibus database. Differential gene analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were employed to investigate 38 samples. The copy number variation level exhibited by GC cells was determined using InferCNV. The CytoTRACE, Monocle and Slingshot analysis were used to discern the cellular stemness and developmental trajectory of GC cells. The CellChat package was utilized for the analysis of intercellular communication crosstalk. Moreover, the findings of the data analysis were validated through cellular functional tests conducted on the AGS cell line and SGC-7901 cell line. Finally, this study constructed a risk scoring model to evaluate the differences of different risk scores in clinical characteristics, immune infiltration, immune checkpoints, functional enrichment, tumour mutation burden and drug sensitivity. Within the microenvironment of GC, we identified the presence of 8 cell subsets, encompassing NK_T cells, B_Plasma cells, epithelial cells, myeloid cells, endothelial cells, mast cells, fibroblasts, pericytes. By delving deeper into the characterization of GC cells, we identified 6 specific tumour cell subtypes: C0 PSCA+ tumour cells, C1 CLDN7+ tumour cells, C2 UBE2C+ tumour cells, C3 MUC6+ tumour cells, C4 CHGA+ tumour cells and C5 MUC2+ tumour cells. Notably, the C2 UBE2C+ tumour cells demonstrated a close association with cell mitosis and the cell cycle, exhibiting robust proliferative capabilities. Our findings were fortified through enrichment analysis, pseudotime analysis and cell communication analysis. Meanwhile, knockdown of the transcription factor CREB3, which is highly active in UBE2C+ tumour cells, significantly impedes the proliferation, migration and invasion of GC cells. And the prognostic score model constructed with CREB3-related genes showcased commendable clinical predictive capacity, thus providing valuable guidance for patients' prognosis and clinical treatment decisions. We have identified a highly proliferative cellular subgroup C2 UBE2C+ tumour cells in GC for the first time. The employment of a risk score model, which is based on genes associated with UBE2C expression, exhibits remarkable proficiency in predicting the prognosis of GC patients. In our investigation, we observed that the knockdown of the transcription factor CREB3 led to a marked reduction in cellular proliferation, migration and invasion in GC cell line models. Implementing a stratified treatment approach guided by this model represents a judicious and promising methodology.


Asunto(s)
Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Análisis de la Célula Individual , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/genética , Proliferación Celular/genética , Análisis de la Célula Individual/métodos , Línea Celular Tumoral , Perfilación de la Expresión Génica , Variaciones en el Número de Copia de ADN/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Comunicación Celular/genética
6.
J Neurosci ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871463

RESUMEN

Inter-species comparisons are key to deriving an understanding of the behavioral and neural correlates of human cognition from animal models. We perform a detailed comparison of the strategies of female macaque monkeys to male and female humans on a variant of the Wisconsin Card Sort Test (WCST), a widely studied and applied task that provides a multi-attribute measure of cognitive function and depends on the frontal lobe. WCST performance requires the inference of a rule change given ambiguous feedback. We found that well-trained monkeys infer new rules three times more slowly than minimally instructed humans. Input-dependent Hidden Markov Model-Generalized Linear Models were fit to their choices, revealing hidden states akin to feature-based attention in both species. Decision processes resembled a Win-Stay Lose-Shift strategy with inter-species similarities as well as key differences. Monkeys and humans both test multiple rule hypotheses over a series of rule-search trials and perform inference-like computations to exclude candidate choice options. We quantitatively show that perseveration, random exploration and poor sensitivity to negative feedback account for the slower task-switching performance in monkeys.Significance Statement Advances in training and recording from animal models support the study of increasingly complex behaviors in non-humans. Before interpreting their neural computations as human-like, we must first ascertain whether their computational algorithms are human-like. We compared rapid rule-learning strategies of macaque monkeys and humans on a Wisconsin Card Sorting Test variant and found that monkeys are 3-4 times slower than humans at learning new rules. Model fits to choice behavior revealed that both species use qualitatively similar exploration strategies with different decision criteria. These differences produced distinct errors in monkeys that are similar to those observed in humans with prefrontal deficits. Our results generate detailed neural hypotheses and highlight the need for systematic inter-species behavioral and neural comparisons.

7.
Medicine (Baltimore) ; 103(24): e38412, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38875406

RESUMEN

BACKGROUND: This study aimed to evaluate the impact of a resistance exercise program in the bedridden older adults in China. METHODS: The patients aged 80 years and above with stable diseases were randomly divided into control group (receiving routine treatment and nursing) and training group (receiving the elastic ball and elastic band training applied for 55 minutes, 3 times a week during 6 months). RESULTS: A total of 59 patients (control group: 30; training groups: 29) completed the study. In terms of muscle strength, the patients of the training group had better grip strength and supine leg lifts and 30-s sit-to-stand actions. In terms of cardiopulmonary function and glycolipid metabolism, the patients in the training groups had better lung capacity and high-density lipoprotein. CONCLUSION: The low-load and low-intensity resistance training may effectively improve not only the muscle strength of the bedridden older adults, but also the lung function and blood lipid metabolism.


Asunto(s)
Glucolípidos , Fuerza Muscular , Entrenamiento de Fuerza , Humanos , Masculino , Femenino , Fuerza Muscular/fisiología , Entrenamiento de Fuerza/métodos , Anciano de 80 o más Años , Glucolípidos/metabolismo , Personas Encamadas , China , Fuerza de la Mano/fisiología , Pruebas de Función Respiratoria
8.
Curr Microbiol ; 81(7): 185, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771339

RESUMEN

The plastic film is extensively applied with limited recycling, leading to the long-run residue accumulation in soil, which offers a distinctive habitat for microorganisms, and creates a plastisphere. In this study, traditional low-density polyethylene (LDPE) plastic film and biodegradable polybutylene adipate terephthalate (PBAT) plastic film materials were selected to test their effects on soil microbial ecology. Based on high-throughput sequencing, compared to the soil environment, the alpha-diversity of bacterial communities in plastisphere was lower, and the abundance of Actinobacteria increased. Plastic film residues, as bacterial habitats, exhibited greater heterogeneity and harbor unique bacterial communities. The communities were distinguished between plastisphere and soil environment by means of a random-forest (RF) machine-learning model. Prominent distinctions emerged among bacterial functions between soil environment and plastisphere, especially regarding organics degradation. The neutral model and null model indicated that the constitution of bacterial communities was dominated by random processes except in LDPE plastisphere. The bacterial co-occurrence network of the plastisphere exhibited higher complexity and modularity. This study contributes to our comprehending of characteristics of plastisphere bacterial communities in soil environment and the associated ecological risks of plastic film residues accumulation.


Asunto(s)
Bacterias , Polietileno , Microbiología del Suelo , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Polietileno/química , Poliésteres/metabolismo , Suelo/química , Contaminantes del Suelo/análisis , Microbiota
9.
Sci Rep ; 14(1): 12228, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806610

RESUMEN

DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/ß-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , ADN-Topoisomerasas de Tipo II , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Proteínas de Unión a Poli-ADP-Ribosa , ADN-Topoisomerasas de Tipo II/metabolismo , ADN-Topoisomerasas de Tipo II/genética , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transición Epitelial-Mesenquimal/genética , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/genética , Movimiento Celular/genética , Línea Celular Tumoral , Metástasis de la Neoplasia , Vía de Señalización Wnt , Apoptosis , Masculino , Femenino , Persona de Mediana Edad , Proteína Wnt3A/metabolismo , Proteína Wnt3A/genética
10.
Open Life Sci ; 19(1): 20220864, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737104

RESUMEN

The application of fertilizers and soil quality are crucial for grape fruit quality. However, the molecular data linking different fertilizer (or soil conditioner [SC]) treatments with grape fruit quality is still lacking. In this study, we investigated three soil treatments, namely inorganic fertilizer (NPK, 343.5 kg/hm2 urea [N ≥ 46%]; 166.5 kg/hm2 P2O5 [P2O5 ≥ 64%]; 318 kg/hm2 K2O [K2O ≥ 50%]), organic fertilizer (Org, 9 t/hm2 [organic matter content ≥ 35%, N + P2O5 + K2O ≥ 13%]), and SC (SC, 3 t/hm2 [humic acid ≥ 38.5%; C, 56.1%; H, 3.7%; N, 1.5%; O, 38%; S, 0.6%]), on 4-year-old Cabernet Sauvignon grapevines. Compared with the NPK- and Org-treated groups, the SC significantly improved the levels of soluble solids, tannins, anthocyanins, and total phenols in the grape berries, which are important biochemical indicators that affect wine quality. Furthermore, we conducted RNA-seq analysis on the grapevine roots from each of the three treatments and used weighted gene co-expression network analysis to identify five hub genes that were associated with the biochemical indicators of the grape berries. Furthermore, we validated the expression levels of three hub genes (ERF, JP, and SF3B) and five selected genes related to anthocyanin biosynthesis (UFGT1, UFGT2, UFGT3, GST, and AT) by using quantitative reverse transcription-polymerase chain reaction. Compared to the NPK and Org treatment groups, the SC treatment resulted in a significant increase in the transcription levels of three hub genes as well as VvUFGT1, VvUFGT3, VvGST, and VvAT. These results suggest that the SC can improve grape fruit quality by altering gene transcription patterns in grapevine roots and further influence the biochemical indices of grape fruits, particularly anthocyanin content. This study reveals that the application of SC can serve as an important measure for enhancing vineyard SC and elevating grape quality.

11.
Cell Mol Biol Lett ; 29(1): 70, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741147

RESUMEN

BACKGROUND: Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown. METHODS: Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC‒MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in Escherichia coli by genetic engineering technology using pET-28a as a plasmid and purified by Ni-NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of γδ T cells and major γδ T-cell subset types as well as the production of TNF-α and IFN-γ were determined by flow cytometry. Their proliferating γδ T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified γδ T cells to quantify Mycobacterium viability by counting CFUs. RESULTS: In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC‒MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by Escherichia coli genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced γδ T-cell expansion, with Vγ2δ2 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-α and IFN-γ. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote γδ T-cell proliferation and the secretion of TNF-α and IFN-γ. None of the above recombinant proteins were able to induce the secretion of TNF-α and IFN-γ by αß T cells. In addition, TNF-α, IFN-γ-producing γδ T cells inhibit the growth of intracellular Mtb. CONCLUSION: Activated γδ T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-α, IFN-γ modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces γδ T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.


Asunto(s)
Antígenos Bacterianos , Proliferación Celular , Mycobacterium tuberculosis , Linfocitos T , Humanos , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/metabolismo , Antígenos Bacterianos/genética , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Interferón gamma/metabolismo , Interferón gamma/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Factor de Necrosis Tumoral alfa/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología
12.
Cereb Cortex ; 34(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38771244

RESUMEN

The recent publications of the inter-areal connectomes for mouse, marmoset, and macaque cortex have allowed deeper comparisons across rodent vs. primate cortical organization. In general, these show that the mouse has very widespread, "all-to-all" inter-areal connectivity (i.e. a "highly dense" connectome in a graph theoretical framework), while primates have a more modular organization. In this review, we highlight the relevance of these differences to function, including the example of primary visual cortex (V1) which, in the mouse, is interconnected with all other areas, therefore including other primary sensory and frontal areas. We argue that this dense inter-areal connectivity benefits multimodal associations, at the cost of reduced functional segregation. Conversely, primates have expanded cortices with a modular connectivity structure, where V1 is almost exclusively interconnected with other visual cortices, themselves organized in relatively segregated streams, and hierarchically higher cortical areas such as prefrontal cortex provide top-down regulation for specifying precise information for working memory storage and manipulation. Increased complexity in cytoarchitecture, connectivity, dendritic spine density, and receptor expression additionally reveal a sharper hierarchical organization in primate cortex. Together, we argue that these primate specializations permit separable deconstruction and selective reconstruction of representations, which is essential to higher cognition.


Asunto(s)
Callithrix , Cognición , Conectoma , Macaca , Animales , Ratones , Cognición/fisiología , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Corteza Cerebral/fisiología
13.
medRxiv ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38746245

RESUMEN

Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients. Methods: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCC in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Additionally, serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC. Results: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/ß-catenin pathway. The TERT promoter mutation frequency was also remarkably high in the Hispanic cohort. Cell cycles and liver functions were identified as positively- and negatively-enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in the serum samples of HCC patients. Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. The subtype with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. It also had higher levels of immune checkpoint and immune exhaustion markers. Conclusions: Our study revealed some specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management of HCC and provides a unique resource for studying Hispanic HCC.

14.
J Int Med Res ; 52(5): 3000605241241000, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38749910

RESUMEN

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.


Asunto(s)
Colitis , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Ileostomía , Humanos , Masculino , Anciano , Trasplante de Microbiota Fecal/métodos , Colitis/microbiología , Colitis/terapia , Trasplante Homólogo/métodos , Resultado del Tratamiento , Colonoscopía
15.
Clin Transl Med ; 14(5): e1680, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38769668

RESUMEN

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.


Asunto(s)
Proteínas Proto-Oncogénicas c-myc , Humanos , Ratones , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Animales , Ácido Aspártico/metabolismo , Malatos/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/genética , Progresión de la Enfermedad , Activación Transcripcional/genética , Línea Celular Tumoral , Modelos Animales de Enfermedad
16.
BMC Cancer ; 24(1): 633, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783271

RESUMEN

BACKGROUND: PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types. METHODS: The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures. RESULTS: In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown. CONCLUSIONS: Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Técnicas de Silenciamiento del Gen , Neoplasias Pulmonares , Neovascularización Patológica , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , Humanos , Transición Epitelial-Mesenquimal/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Línea Celular Tumoral , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Masculino , Femenino , Células A549 , Persona de Mediana Edad
17.
Plants (Basel) ; 13(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38611476

RESUMEN

To explore the population structures and dynamics of Rhododendron shrub communities at different stages of succession in northwest Guizhou, China, this study examined the populations of Rhododendron annae and Rhododendron irroratum shrub with two different stages. A space-for-time substitution was employed to establish the diameter class/height structures, static life tables, and survival/mortality rate/disappearance rate curves of both Rhododendron populations with different orders of succession. Their structural and quantitative dynamics were analyzed, and their development trends were predicted. The results showed that, quantitatively, the populations of R. annae and R. irroratum in the two Rhododendron communities with different orders of succession were dominated by age classes one, two, and three as well as height classes i, ii, and iii. The number of Rhododendron plants at the three age classes and the three height classes accounted for 97.61-100% of the total. The quantitative dynamic indices of R. annae and R. irroratum were both greater than 0, with and without considering external interference. In terms of age class and height structures, both Rhododendron populations were expanding populations, presenting "inverted-J-shaped" and irregular pyramid patterns. There was a sufficient number of young individuals, but few or no old individuals. Both survival curves of the populations of R. annae and R. irroratum in the two Rhododendron communities with different orders of succession belonged to the Deevy-II type. In the late stage of succession, the mortality curves and disappearance curves of both Rhododendron populations in these communities presented a trend of increasing first and then decreasing with increasing age class. This result indicates that at each age class, R. annae and R. irroratum showed a trend of gradual increase after two, four, and six years. In brief, the populations of R. annae and R. irroratum have rich reserves of seedlings and saplings, but high mortality and disappearance rates. In this context, it is necessary to reduce human interference and implement targeted conservation measures to promote the natural renewal of Rhododendron populations.

18.
J Prosthet Dent ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38627178

RESUMEN

Precise implant placement is key to ensuring the success of dental implant surgery. Implant robotic systems have been increasingly adopted for clinical procedures because of their accuracy. Maxillary sinus floor elevation with the Disk-up Sinus Reamer (DSR) may be an effective solution for inadequate posterior maxillary bone height. This clinical treatment combined with an autonomous implant robot with DSR for maxillary sinus floor elevation with simultaneous dental implant surgery may be suitable for clinical practice.

19.
Infect Drug Resist ; 17: 1323-1332, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585416

RESUMEN

Purpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child. Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed. Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1-7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P>0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P<0.05). Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1-7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.

20.
J Prosthet Dent ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38570281

RESUMEN

Precise reproduction of the preoperatively designed 3-dimensional (3D) implant position is key to seating a prefabricated restoration and restoring esthetics. Static and dynamic computer-aided implant surgery (CAIS) based on the fusion of 3D imaging files have been used to improve implant accuracy. However, both techniques have shortcomings that can be remedied by a robotic system. This clinical report describes the immediate placement of an implant in the anterior esthetic zone by using an autonomous dental implant robotic system (ADIR).

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