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2.
Neural Netw ; 180: 106745, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39340967

RESUMO

In data analysis and forecasting, particularly for multivariate long-term time series, challenges persist. The Transformer model in deep learning methods has shown significant potential in time series forecasting. The Transformer model's dot-product attention mechanism, however, due to its quadratic computational complexity, impairs training and forecasting efficiency. In addition, the Transformer architecture has limitations in modeling local features and dealing with multivariate cross-dimensional dependency relationship. In this article, a Multi-Scale Convolution Enhanced Transformer model (MSCformer) is proposed for multivariate long-term time series forecasting. As an alternative to modeling the time series in its entirety, a segmentation strategy is designed to convert the input original series into segmented forms with different lengths, then process time series segments using a new constructed multi-Dependency Aggregation module. This multi-Scale segmentation approach reduces the computational complexity of the attention mechanism part in subsequent models, and for each segment of length corresponds to a specific time scale, it also ensures that each segment retains the semantic information of the data sequence level, thereby comprehensively utilizing the multi-scale information of the data while more accurately capturing the real dependency of the time series. The Multi-Dependence Aggregate module captures both cross-temporal and cross-dimensional dependencies of multivariate long-term time series and compensates for local dependencies within the segments thereby captures local series features comprehensively and addressing the issue of insufficient information utilization. MSCformer synthesizes dependency information extracted from various temporal segments at different scales and reconstructs future series using linear layers. MSCformer exhibits higher forecasting accuracy, outperforming existing methods in multiple domains including energy, transportation, weather, electricity, disease and finance.

3.
BMC Gastroenterol ; 24(1): 329, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350092

RESUMO

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) patients are at an elevated risk of developing severe coronavirus disease 2019 (COVID-19). The objective of this study was to assess antibody responses and safety profiles six months after the third dose of the inactivated acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in MASLD patients. METHODS: This study included MASLD patients and healthy volunteers without a history of SARS-CoV-2 infection. Blood samples were collected six months after receiving the third dose of the inactivated vaccine to measure the levels of neutralizing antibodies (NAbs) and anti-spike IgG antibodies against SARS-CoV-2. RESULTS: A total of 335 participants (214 MASLD patients and 121 healthy volunteers) were enrolled. The seroprevalence of NAb was 61.7% (132 of 214) in MASLD patients and 74.4% (90 of 121) in healthy volunteers, which was a significant difference (p = 0.018). Statistically significant differences in IgG seroprevalence were also observed between MASLD patients and healthy volunteers (p = 0.004). Multivariate analysis demonstrated that the severity of MASLD (OR, 2.97; 95% CI, 1.32-6.68; p = 0.009) and age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.004) were independent risk factors for NAb negativity in MASLD patients. Moderate/severe MASLD patients had a lower NAb seroprevalence than mild MASLD patients (45.0% vs. 65.5%, p = 0.016). CONCLUSION: Lower antibody responses were observed in MASLD patients six months after their third dose of the inactivated vaccine than in healthy volunteers, providing further assistance in monitoring patients who are more vulnerable to hypo-responsiveness to SARS-CoV-2 vaccines.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Vacinas de Produtos Inativados , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Adulto , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Idoso , Formação de Anticorpos/imunologia , Estudos Soroepidemiológicos
4.
Environ Sci Technol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39322606

RESUMO

Triclocarban (TCC), as a typical antimicrobial agent, accumulates at substantial levels in natural environments and engineered systems. This work investigated the impact of TCC on anaerobic sulfur transformation, especially toxic H2S production. Experimental findings revealed that TCC facilitated sulfur flow from the sludge solid phase to liquid phase, promoted sulfate reduction and sulfur-containing amino acid degradation, and largely improved anaerobic H2S production, i.e., 50-600 mg/kg total suspended solids (TSS) TCC increased the cumulative H2S yields by 24.76-478.12%. Although TCC can be partially biodegraded in anaerobic systems, the increase in H2S production can be mainly attributed to the effect of TCC rather than its degradation products. TCC was spontaneously adsorbed by protein-like substances contained in microbe extracellular polymers (EPSs), and the adsorbed TCC increased the direct electron transfer ability of EPSs, possibly due to the increase in the content of electroactive polymer protein in EPSs, the polarization of the amide group C═O bond, and the increase of the α-helical peptide dipole moment, which might be one important reason for promoting sulfur bioconversion processes. Microbial analysis showed that the presence of TCC enriched the organic substrate-degrading bacteria and sulfate-reducing bacteria and increased the abundances of functional genes encoding sulfate transport and dissimilatory sulfate reduction.

5.
Plant Physiol Biochem ; 216: 109155, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39332328

RESUMO

Microplastics (MPs) are important carriers of various toxic metals and can alter their toxicity pattern in agricultural soil, leading to combined pollution, therefore posing new challenges to soil pollution management and environmental risk assessment. In this study, we observed the internalization of MPs in plants and conducted incubation experiments to evaluated the effects of arsenate (As(V)) alone and in combination with polystyrene (PS) MPs on wheat seedlings (Triticum aestivum L.). Under As(V) alone and combined with PS-MP exposure, dose-dependent toxicity in terms of root and stem elongation and biomass accumulation was observed. Compared with As(V) alone, the presence of PS-MPs reduced the accumulation of As in wheat roots by 11.43-58.91%, but PS-MPs intensified the transport of As to the aboveground parts of wheat, increasing As accumulation in wheat stems by 27.77-1011.54%. This causes more serious mechanical damage and oxidative stress to plant cells, increasing the accumulation of reactive oxygen species and lipid peroxidation in wheat roots and upregulating the activities of antioxidant enzymes such as superoxide dismutase (SOD) and peroxidase (POD). In addition, the co-exposure of As(V) and PS-MPs disrupts the photosynthetic system of wheat leaves and the secretion activities of roots. Therefore, the combination of As(V) and PS-MPs caused greater damage to wheat growth. Our findings contribute to a more comprehensive assessment of the combined toxicity of MPs and heavy metal to crops.

6.
ACS Appl Bio Mater ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250682

RESUMO

Diabetic foot ulcer (DFU) is a common and severe complication of diabetes characterized by wound neuropathy, ischemia, and susceptibility to infection, making its treatment difficult. Dressings are commonly used in treating diabetic wounds; however, they have disadvantages, including lack of flexibility and mechanical strength, lack of coagulation activity, resistance to biodegradation, and low drug delivery efficiency. Developing more effective strategies for diabetic wound treatment has become a new focus. Microneedles (MN) can be used as a drug delivery platform for DFU wounds, allowing safe, effective, painless and minimally invasive medication administration through the skin. Herein, PDA@Ag/SerMA microneedles were prepared by combining the photothermal properties of polydopamine (PDA), the antimicrobial properties of argentum (Ag), and the ability of sericin methacryloyl (SerMA) to promote cell mitosis to accelerate wound healing and treat diabetic ulcer wounds. The results revealed that PDA@Ag/SerMA microneedles exhibited approximately 100% antimicrobial efficacy against Staphylococcus aureus and Escherichia coli under 808 nm near-infrared (NIR) irradiation. Furthermore, the wound healing rate of mice reached 95% within 12 days, which demonstrated the excellent antibacterial properties and wound healing efficacy of PDA@Ag/SerMA microneedles at cellular and animal levels, providing a potential solution for treating DFU.

7.
Water Res ; 267: 122464, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39303578

RESUMO

The addition of iron-based conductive materials has been extensively validated as a highly effective approach to augment methane generation from anaerobic digestion (AD) process. In this work, it was additionally discovered that Fe3O4 notably suppressed the production of hazardous H2S gas during sludge AD. As the addition of Fe3O4 increased from 0 to 20 g/L, the accumulative H2S yields decreased by 89.2 % while the content of element sulfur and acid volatile sulfide (AVS) respectively increased by 55.0 % and 30.4 %. Mechanism analyses showed that the added Fe3O4 facilitated sludge conductive capacity, and boosted the efficiency of extracellular electron transfer, which accelerated the bioprocess of sulfide oxidation. Although Fe3O4 can chemically oxidize sulfide to elemental sulfur, microbial oxidation plays a major role in reducing H2S accumulation. Moreover, the released iron ions reacted with soluble sulfide, which promoted the chemical equilibrium of sulfide species from H2S to metal sulfide. Microbial analysis showed that some SRBs (i.e., Desulfomicrobium and Defluviicoccus) and SOB (i.e., Sulfuritalea) changed into keystone taxa (i.e., connectors and module hubs) in the reactor with Fe3O4 addition, showing that the functions of sulfate reduction and sulfur oxidation may play important roles in Fe3O4-present system. Fe3O4 presence also increased the content of functional genes encoding sulfide quinone reductase and flavocytochrome c sulfidedehydrogenase (e.g., Sqr and Fcc) that could oxidize sulfide to sulfur. The impact of other iron-based conductive material (i.e., zero-valent iron) was also verified, and the results showed that it could also significantly reduce H2S production. These findings provide new insights into the effect of iron-based conductive materials on anaerobic process, especially sulfur conversion.

8.
Int J Pharm ; : 124732, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39304093

RESUMO

As people's living standards continue to improve and human life span expectancy increases, the incidence and mortality rates of breast cancer are continuously rising. Early detection of breast cancer and targeted therapy for different breast cancer subtypes can significantly reduce the mortality rate and alleviate the suffering of patients. Exosomes are extracellular vesicles secreted by various cells in the body. They participate in physiological and pathological responses by releasing active substances and play an important role in regulating intercellular communication. In recent years, research on exosomes has gradually expanded, and their special membrane structure and targetable characteristics are being increasingly applied in various clinical studies. Mesenchymal stem cells (MSCs)-derived exosomes play an important role in regulating the progression of breast cancer. In this review, we summarize the current treatment methods for breast cancer, the connection between MSCs, exosomes, and breast cancer, as well as the application of exosomes derived from MSCs from different sources in cancer treatment. We highlight how the rational design of modified MSCs-derived exosomes (MSCs-Exos) delivery systems can overcome the uncertainties of stem cell therapy and overcome the clinical translation challenges of nanomaterials. This work aims to promote future research on the application of MSCs-Exos in breast cancer treatment.

9.
Cancer Med ; 13(18): e70253, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39344563

RESUMO

BACKGROUND: Investigating the molecular mechanism of colorectal cancer (CRC), a common lethal malignancies worldwide, is of great clinical significance. Solute carrier family 25 member 19 (SLC25A19) is a member of the solute carrier family that contribute to cellular functions, including tumor biology. Recently, many studies have attention on uncovering the relationship of SLC25A19 with malignant cancers, but its precise involvement in the regulation of CRC has not been thoroughly understood. This study sought to uncover the role and mechanism of SLC25A19 in CRC development. METHODS: The GEPIA database and immunohistochemical staining were utilized to detect the expression of SLC25A19 in CRC tissues. The functional influences of SLC25A19 on CRC cell phenotypes were evaluated through a series of assays including celigo cell count, colony formation, CCK-8, flow cytometry, wound healing, and transwell assays following knocking down SLC25A19. Subsequently, the xenograft tumor model was constructed to evaluate the effect of SLC25A19 on tumor growth in vivo. The underlying mechanisms of SLC25A19 silencing were investigated using the human phospho-kinase array. RESULTS: This study demonstrated the upregulation of SLC25A19 in CRC and its significant correlation with unfavorable prognosis in CRC patients. Suppression of SLC25A19 resulted in significant inhibition of cell proliferation, colony formation, and cell migration, alongside a boost in cell apoptosis. In vivo experiments revealed that silenced SLC25A19 displayed reduced growth rates and formed smaller xenografts. Mechanistically, the p53 pathway was found to be upregulated by SLC25A19 knockdown and mediated the function of SLC25A19. CONCLUSIONS: Consequently, SLC25A19 was identified as a novel molecule with key regulatory ability in CRC development.


Assuntos
Proliferação de Células , Neoplasias Colorretais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Proteína Supressora de Tumor p53 , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Animais , Camundongos , Linhagem Celular Tumoral , Prognóstico , Apoptose , Camundongos Nus , Movimento Celular , Feminino , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C
10.
Biology (Basel) ; 13(9)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39336176

RESUMO

One of the crucial factors influencing the growth and viability of larvae and juveniles is their opening diets. The objective of this study was to identify suitable initial feed options for M. macropterus larvae and juveniles. A total of 1200 newly hatched M. macropterus with an average weight of 18.3 mg and an average length of 11.58 mm were selected and randomly divided into four groups. The fish were fed with different opening diets, including rotifer, Artemia nauplii, Tubifex, and micro-diet from six days after hatching (dahs), respectively. Growth indices and activities of digestive enzymes were assessed at 10, 15, 20, 25, 30, 35, and 40 dahs. Histological examination of the structure of the digestive tract was performed at 40 dahs, while survival rates were also documented. The results demonstrated that different diets had no effect on the survival rate of larvae and juveniles of M. macropterus. The growth performance indices were ranked as follows: Tubifex group > Artemia nauplii group > micro-diet group > rotifer group. Remarkably, the Tubifex group exhibited superior growth performance, which was also reflected in the structure of the digestive tract and digestive enzyme activity. Therefore, it is recommended to include Tubifex in the diet of M. macropterus larvae and juvenile during the standardized farming process.

11.
Science ; 385(6714): 1217-1224, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39264996

RESUMO

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo-electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D2- and D4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions.


Assuntos
Capsídeo , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Vírion , Humanos , Capsídeo/química , Capsídeo/ultraestrutura , Microscopia Crioeletrônica , Antígenos de Superfície da Hepatite B/química , Vírus da Hepatite B/ultraestrutura , Vírus da Hepatite B/química , Vírus da Hepatite B/fisiologia , Multimerização Proteica , Envelope Viral/química , Envelope Viral/ultraestrutura , Vírion/ultraestrutura , Vírion/química , Montagem de Vírus , Hepatite B Crônica/virologia , Conjuntos de Dados como Assunto
12.
Environ Sci Pollut Res Int ; 31(39): 51364-51380, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39110285

RESUMO

Heat stress (HS) causes severe economic losses in sheep industry worldwide. The objective of the present study was to investigate the effects of a herbal formula (HF) supplement on growth, digestibility, antioxidant capacity, and rumen microbes in fattening lambs under HS. The HF composed of four herbs was prepared based on the theory of compatibility of Chinese medicine "Jun-Chen-Zuo-Shi". Two-hundred forty 3-month weaned lambs (initial weight 36.61 ± 0.73 kg) were randomly allocated into four groups, supplemented 0% (Control), 0.5%, 1.0%, and 1.5% HF in diets. All lambs were exposed to HS conditions with 79.7 of average temperature-humidity index throughout an experimental period of 35 days. Growth performance, apparent digestibility, and antioxidant activities, involving antioxidant enzymes and heat shock proteins (HSPs), were measured at the end of trial, as well as microbial communities in bacteria and archaea. Results showed that 0.5% HF increased (P = 0.02) average daily gain by 13.80% and decreased feed-to-gain ratio (P = 0.03) by 14.68%, compared to control. With increasing HF doses, the digestibility of ether extract and acid detergent fiber demonstrated a cubical (P < 0.01) and quadratic (P = 0.03) relation, respectively; moreover, glutathione peroxidase and catalase activities demonstrated a quadratic increase (P < 0.01). Serum levels of HSP60, HSP70, and HSP90 for 0.5% HF were lower than that in control (P < 0.05). On the other hand, total volatile fatty acid, acetic acid, butyric acid, valeric acid, and isovaleric acid levels exhibited quadratic increases (P ≤ 0.01) with HF doses. From rumen microbes, the abundance and diversity of bacterial community were improved by HF supplements. Particularly for 0.5% HF group, the operational taxonomic units were the greatest among all groups. Compared to control, Prevotella abundance for HF supplements from 0.5 to 1.5% increased by 35.57 to 60.15%, and Succiniclasticum abundance demonstrated a quadratic pattern (P = 0.02) with doses. Additionally, Methanosphaera abundance in archaeal community raised by 0.2 to 3.3-folds when lambs were fed the HF additions of 0.5 to 1.5%. In summary, dietary HF supplements would contribute to alleviating HS in lambs, and our results suggest the optimal dose of 0.5% HF supplement in diet.


Assuntos
Ração Animal , Antioxidantes , Rúmen , Animais , Ovinos , Antioxidantes/metabolismo , Rúmen/microbiologia , Dieta/veterinária , Digestão/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Suplementos Nutricionais , Microbiota/efeitos dos fármacos
13.
Xenobiotica ; : 1-11, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39126503

RESUMO

This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved.Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions.Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar.P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice.

14.
Redox Biol ; 76: 103295, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39159596

RESUMO

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). The authors reached out to the Publisher to alert the Publisher to incorrect text published in the article. After investigating the situation, the journal came to the conclusion that the wrong version of the file was sent by the authors to the production team during the proof stage and the misplaced text was not noticed by the authors when they approved the final version. After consulting with the Editor-in-Chief of the journal, the decision was made to withdraw the current version of the article.

15.
16.
Proc Natl Acad Sci U S A ; 121(35): e2321204121, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39172782

RESUMO

Upon DNA damage, numerous proteins are targeted for ubiquitin-dependent proteasomal degradation, which is an integral part of the DNA repair program. Although details of the ubiquitination processes have been intensively studied, little is known about whether and how the 26S proteasome is regulated in the DNA damage response (DDR). Here, we show that human Rpn10/PSMD4, one of the three ubiquitin receptors of the 26S proteasome, is rapidly phosphorylated in response to different types of DNA damage. The phosphorylation occurs at Rpn10-Ser266 within a conserved SQ motif recognized by ATM/ATR/DNA-PK. Blockade of S266 phosphorylation attenuates homologous recombination-mediated DNA repair and sensitizes cells to genotoxic insults. In vitro and in cellulo experiments indicate that phosphorylation of S266, located in the flexible linker between the two ubiquitin-interacting motifs (UIMs) of Rpn10, alters the configuration of UIMs, and actually reduces ubiquitin chain (substrate) binding. As a result, essential DDR proteins such as BRCA1 are spared from premature degradation and allowed sufficient time to engage in DNA repair, a scenario supported by proximity labeling and quantitative proteomic studies. These findings reveal an inherent self-limiting mechanism of the proteasome that, by controlling substrate recognition through Rpn10 phosphorylation, fine-tunes protein degradation for optimal responses under stress.


Assuntos
Dano ao DNA , Reparo do DNA , Complexo de Endopeptidases do Proteassoma , Complexo de Endopeptidases do Proteassoma/metabolismo , Humanos , Fosforilação , Ubiquitina/metabolismo , Proteína BRCA1/metabolismo , Especificidade por Substrato , Ubiquitinação , Proteínas de Ligação a RNA
17.
Sci Rep ; 14(1): 18077, 2024 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103432

RESUMO

Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration-response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain.


Assuntos
Canais Iônicos Sensíveis a Ácido , Gânglios Espinais , Insulina , Receptor de Insulina , Células Receptoras Sensoriais , Animais , Canais Iônicos Sensíveis a Ácido/metabolismo , Insulina/metabolismo , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/citologia , Ratos , Receptor de Insulina/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Ratos Sprague-Dawley , Hiperalgesia/metabolismo , Células Cultivadas
18.
Nutrition ; 127: 112551, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39181080

RESUMO

OBJECTIVES: The prognostic effects of the Patient-Generated Subjective Global Assessment (PG-SGA) criteria in cancer survivors have been observed but require validation in clinical practice. This study was designed to evaluate the prognostic effects of baseline and longitudinal changes in PG-SGA scores on all-cause mortality among Chinese cancer patients in a real-world setting. METHODS: Study patients were selected from one representative tertiary hospital in West China. Kaplan-Meier curves and Cox regression analyses were used to estimate the prognostic effect of baseline and dynamic changes in PG-SGA scores on the all-cause mortality of cancer patients. Receiver operating characteristic curves and a concordance index were used to evaluate the predictive accuracy of PG-SGA criteria. RESULTS: A total of 1415 cancer patients were included in this study, with a mean age of 46 years old. Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients (PG-SGA 4-8: hazard ratio [HR] = 1.46, 95% confidence interval [CI]: 1.09-1.96, P = 0.012; PG-SGA ≥9: HR = 1.78, 95% CI: 1.34-2.37, P < 0.001). Cancer patients with longitudinal increased PG-SGA scores (>2 points) were observed to have high risks for mortality (HR = 1.69, 95% CI: 1.04-2.74, P = 0.033). Compared with longitudinal changes in PG-SGA scores, baseline malnourished status showed higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586). Sensitivity analyses supported the main findings. CONCLUSIONS: This study highlights the prognostic value of baseline and dynamic changes in PG-SGA scores for cancer patients, which can help improve their outcomes.


Assuntos
Desnutrição , Neoplasias , Avaliação Nutricional , Estado Nutricional , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Neoplasias/mortalidade , Estudos Longitudinais , China/epidemiologia , Prognóstico , Desnutrição/mortalidade , Desnutrição/diagnóstico , Adulto , Sobreviventes de Câncer/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estimativa de Kaplan-Meier , Causas de Morte , Curva ROC , Idoso
19.
MedComm (2020) ; 5(9): e692, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39170945

RESUMO

Understanding the endogenous mechanism of adaptive response to drug-induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin-induced liver injury (TILI) of mice. Exosomal miR-106b-5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR-106b-5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR-106b-5p protects mice from liver injury. Injured hepatocytes released miR-106b-5p-enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR-106b-5p by dual luciferase reporter and siRNA assays. Furthermore, single-cell RNA-sequencing analysis of toosendanin-injured mouse liver revealed a cluster of Vim + hepatocytes; nonetheless declined following miR-106b-5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR-106b-5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR-106b-5p safeguards restorative tissue repair by targeting vimentin.

20.
CNS Neurosci Ther ; 30(8): e14915, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39187974

RESUMO

AIMS: To examine whether functional connectivity (FC) of the occipital gyrus differs between patients with Parkinson's disease (PD) motor subtypes and healthy controls (HCs). METHODS: We enrolled 30 PD patients exhibiting tremor dominance (TD), 43 PD patients with postural instability and gait disturbance (PIGD), and 42 HCs. The occipital gyrus was partitioned into six areas of interest, as seed points, via the Anatomical Automatic Labeling template to compare the FC of the three groups and analyze the relationship of FC with clinical scales. RESULTS: Compared with the PIGD group, the TD group showed increased FC between the left superior occipital gyrus (SOG.L) and right median cingulate and paracingulate gyri (DCG.R)/right paracentral lobule/bilateral inferior parietal, but supramarginal and angular gyri; the left middle occipital gyrus (MOG.L) and left posterior cingulate gyrus (PCG.L); the MOG.R and SOG.L/right calcarine fissure and surrounding cortex/DCG.R/PCG.L/right cuneus; the left inferior occipital gyrus (IOG.L) and right caudate nucleus; and the IOG.R and PCG.L. CONCLUSION: Differentiated FC between the occipital gyrus and other brain areas within the PD motor subtypes, which may serve as neural markers to distinguish between patients with TD and PIGD PD.


Assuntos
Vias Neurais , Lobo Occipital , Doença de Parkinson , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Vias Neurais/patologia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos
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