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1.
Artigo em Inglês | MEDLINE | ID: mdl-38570918

RESUMO

CONTEXT: Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. OBJECTIVE: The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. MATERIALS AND METHODS: Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. RESULTS: A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). CONCLUSIONS: PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

2.
Org Biomol Chem ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651658

RESUMO

An efficient and practical method for the synthesis of 3-alkenylquinoxalinones containing the SCF3 group has been readily developed through a three-component radical cascade reaction involving quinoxalinones, alkynes and AgSCF3. The reaction was found to be compatible with a variety of substrates and exhibited a high functional group tolerance and complete E-selectivity. The preliminary study suggests the involvement of a SCF3 radical in the transformation.

3.
Nat Biotechnol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653797

RESUMO

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

4.
Eur J Gastroenterol Hepatol ; 36(5): 608-614, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38477849

RESUMO

BACKGROUND: Consuming sugar-sweetened beverages (SSBs) has been linked to the development of various adverse health conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated associations between SSB intake and long-term mortality among individuals with MASLD using a nationally representative database. METHODS: This population-based, longitudinal study extracted data of adults aged 20-79 years with MASLD from the USA (US) National Health and Nutrition Examination Survey database 2003-2014. Associations between the amount of SSB intake and all-cause, cancer and cardiovascular disease mortality until the end of 2019 were determined using Cox proportional hazards regression analyses. RESULTS: A total of 12 965 individuals aged 20-79 years who had MASLD were identified in the database. After exclusion, 5630 participants remained for the analyses. This cohort can be extrapolated to 43 420 321 individuals in the entire US after proper weighting. The mean age of the study cohort was 44.1 years. After adjusting for confounders, no significant association was observed between SSB intake (tertile 3 vs. tertile 1) and all-cause [adjusted hazard ratio (aHR): 1.03, 95% confidence interval (CI), 0.60-1.76) or cancer mortality (aHR, 0.41; 95% CI, 0.15-1.16). However, higher SSB intake (tertile 3 vs. tertile 1) was significantly associated with elevated cardiovascular disease mortality risk (aHR = 2.83; 95% CI, 1.01-7.91). CONCLUSION: In US adults with MASLD, high SSB intake is associated with nearly three-fold increased cardiovascular disease mortality risk. The findings underscore the critical need for concerted action on the part of healthcare providers and policymakers.


Assuntos
Doenças Cardiovasculares , Hepatopatias , Neoplasias , Bebidas Adoçadas com Açúcar , Adulto , Humanos , Bebidas Adoçadas com Açúcar/efeitos adversos , Bebidas/efeitos adversos , Inquéritos Nutricionais , Estudos Longitudinais
5.
ACS Nano ; 18(12): 8694-8705, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38466230

RESUMO

Small-scale magnetic robots with fixed magnetizations have limited locomotion modes, restricting their applications in complex environments in vivo. Here we present a morphology-reconfigurable millirobot that can switch the locomotion modes locally by reprogramming its magnetizations during navigation, in response to distinct magnetic field patterns. By continuously switching its locomotion modes between the high-velocity rigid motion and high-adaptability soft actuation, the millirobot efficiently navigates in small lumens with intricate internal structures and complex surface topographies. As demonstrations, the millirobot performs multimodal locomotion including woodlouse-like rolling and flipping, sperm-like rotating, and snake-like gliding to negotiate different terrains, including the unrestricted channel and high platform, narrow channel, and solid-liquid interface, respectively. Finally, we demonstrate the drug delivery capability of the millirobot through the oviduct-mimicking phantom and ex vivo oviduct. The magnetization reprogramming strategy during navigation represents a promising approach for developing self-adaptive robots for performing complex tasks in vivo.


Assuntos
Oviductos , Sêmen , Masculino , Feminino , Humanos , Animais , Movimento (Física) , Sistemas de Liberação de Medicamentos , Campos Magnéticos
6.
MAbs ; 16(1): 2322533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38477253

RESUMO

Antibodies have increasingly been developed as drugs with over 100 now licensed in the US or EU. During development, it is often necessary to increase or reduce the affinity of an antibody and rational attempts to do so rely on having a structure of the antibody-antigen complex often obtained by modeling. The antigen-binding site consists primarily of six loops known as complementarity-determining regions (CDRs), and an open question has been whether these loops change their conformation when they bind to an antigen. Existing surveys of antibody-antigen complex structures have only examined CDR conformational change in case studies or small-scale surveys. With an increasing number of antibodies where both free and complexed structures have been deposited in the Protein Data Bank, a large-scale survey of CDR conformational change during binding is now possible. To this end, we built a dataset, AbAgDb, that currently includes 177 antibodies with high-quality CDRs, each of which has at least one bound and one unbound structure. We analyzed the conformational change of the Cα backbone of each CDR upon binding and found that, in most cases, the CDRs (other than CDR-H3) show minimal movement, while 70.6% and 87% of CDR-H3s showed global Cα RMSD ≤ 1.0Å and ≤ 2.0Å, respectively. We also compared bound CDR conformations with the conformational space of unbound CDRs and found most of the bound conformations are included in the unbound conformational space. In future, our results will contribute to developing insights into antibodies and new methods for modeling and docking.


Assuntos
Antígenos , Regiões Determinantes de Complementaridade , Sequência de Aminoácidos , Modelos Moleculares , Conformação Proteica , Regiões Determinantes de Complementaridade/química , Complexo Antígeno-Anticorpo/química , Sítios de Ligação de Anticorpos
7.
Angew Chem Int Ed Engl ; 63(16): e202401255, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38298118

RESUMO

Polylactic acid (PLA) has attracted increasing interest as a sustainable plastic because it can be degraded into CO2 and H2O in nature. However, this process is sluggish, and even worse, it is a CO2-emitting and carbon resource waste process. Therefore, it is highly urgent to develop a novel strategy for recycling post-consumer PLA to achieve a circular plastic economy. Herein, we report a one-pot photoreforming route for the efficient and selective amination of PLA waste into value-added alanine using CoP/CdS catalysts under mild conditions. Results show the alanine production rate can reach up to 2.4 mmol gcat -1 h-1, with a high selectivity (>75 %) and excellent stability. Time-resolved transient absorption spectra (TAS) reveal that CoP can rapidly extract photogenerated electrons from CdS to accelerate proton reduction, favoring hole-dominated PLA oxidation to coproduce alanine. This study offers an appealing way for upcycling PLA waste and creates new opportunities for green synthesis of amino acids.

8.
World J Gastroenterol ; 30(5): 485-498, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38414591

RESUMO

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.


Assuntos
Ferroptose , Neoplasias Gástricas , Animais , Humanos , Ácidos e Sais Biliares , Transdução de Sinais
9.
Nanoscale ; 16(2): 624-634, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38086673

RESUMO

Cancer cells disseminate through the bloodstream, leading to metastasis in distant sites within the body. One promising strategy to prevent metastasis is to eliminate circulating tumor cells. However, this remains challenging due to the lack of an active and targeted biomedical tool for efficient cancer cell elimination. Here, we developed a magnetic microrobot by using natural materials derived from the extracellular matrix (ECM) to mimic the ligand-receptor interaction between cancer cells and the ECM, offering targeted elimination of cancer cells. The ECM-mimicking microrobot is designed with a biodegradable hydrogel matrix, incorporating a cancer cell ligand and magnetic microparticles for cancer cell capture and active locomotion. This microrobot was fabricated based on an interface-shearing method, enabling controllable magnetic response and size scalability (30 µm-500 µm). The presented ECM-mimicking microrobot can actively approach and capture single cancer cells and cell clusters under the control of specific magnetic fields. The experiment was conducted in a blood vessel-mimicking simulator. The microrobot demonstrates an outstanding elimination efficacy of 92.3% on MDA-MB-231 cancer cells and a stable transport capability of the captured cells over long distances to a designed recycling site, inhibiting cell metastasis. This magnetic ECM-mimicking microrobot based on a bioinspired binding mechanism represents a promising candidate for the efficient elimination of cancer cells and other biological waste in the blood.


Assuntos
Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Ligantes , Matriz Extracelular/patologia , Magnetismo , Campos Magnéticos
10.
Am J Clin Oncol ; 47(1): 30-39, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38148710

RESUMO

OBJECTIVE: To evaluate the survival benefit of combining primary tumor resection (PTR) and chemotherapy in patients with unresectable colorectal mucinous adenocarcinoma with liver metastasis (UCR-MAC-LM). METHODS: We obtained data from the surveillance, epidemiology, and end results database for patients with UCR-MAC-LM from 2010 to 2017. Clinicopathological characteristics were analyzed using the χ2 test. Propensity score matching was performed to balance baseline characteristics. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival outcomes. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic factors. RESULTS: A total of 10,178 patients with unresectable colorectal adenocarcinoma with liver metastasis were included, of whom 6.01% (n=612) had UCR-MAC-LM. The UCR-MAC-LM group had a higher proportion of female patients, a greater number of elderly patients, an increased incidence of right colon localization, larger tumor size, and higher T and N staging than the unresectable colorectal non-mucinous adenocarcinoma with liver metastasis group (P<0.05). Multivariate analysis identified several independent prognostic factors (P<0.05). Patients with unresectable colorectal adenocarcinoma with liver metastasis who underwent PTR+C had superior survival rates compared with those who received PTR/C alone or no treatment (cancer-specific survival, P<0.05; overall survival, P<0.05). Subgroup analysis revealed that 17 of 22 groups of patients with UCR-MAC-LM who received PTR+C had significantly prolonged long-term survival compared with those who received PTR/C alone. CONCLUSIONS: This surveillance, epidemiology, and end results-based study indicates that PTR+C may offer a survival advantage for a specific subgroup of patients with UCR-MAC-LM compared with PTR/C alone. Nonetheless, additional clinical trials are necessary to validate these findings.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Feminino , Idoso , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/cirurgia , Estimativa de Kaplan-Meier , Prognóstico , Estudos Retrospectivos
11.
Arch Esp Urol ; 76(9): 690-695, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38053424

RESUMO

BACKGROUND: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. METHODS: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher's exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson's correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. RESULTS: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson's r = -0.228, 95% confidence interval (CI): -0.366 to -0.079, p = 0.003). Logistic regression analysis revealed that the independent risk factor for testicular torsion was TD on admission day (odds ratio, 1.82; 95% CI, 1.28-2.59; p < 0.001). CONCLUSIONS: To some extent, external temperature can affect the body surface temperature of patients and then induce testicular torsion. We concluded that testicular torsion easily occurs in the season in which the temperature drops and the TD is high.


Assuntos
Torção do Cordão Espermático , Humanos , Masculino , Adolescente , Torção do Cordão Espermático/epidemiologia , Torção do Cordão Espermático/etiologia , Estudos Retrospectivos , Temperatura , Temperatura Baixa , Estações do Ano
12.
BMC Anesthesiol ; 23(1): 366, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946114

RESUMO

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.


Assuntos
Anestésicos , Delírio , Adulto , Humanos , Criança , Xenônio/farmacologia , Período Pós-Operatório , Anestesia por Inalação/efeitos adversos , Delírio/induzido quimicamente
13.
Curr Biol ; 33(24): 5355-5367.e5, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-37995699

RESUMO

Soybean (Glycine max) is a crop with high demand for molybdenum (Mo) and typically requires Mo fertilization to achieve maximum yield potential. However, the genetic basis underlying the natural variation of Mo concentration in soybean and its impact on soybean agronomic performance is still poorly understood. Here, we performed a genome-wide association study (GWAS) to identify GmMOT1.1 and GmMOT1.2 that drive the natural variation of soybean Mo concentration and confer agronomic traits by affecting auxin synthesis. The soybean population exhibits five haplotypes of the two genes, with the haplotype 5 demonstrating the highest expression of GmMOT1.1 and GmMOT1.2, as well as the highest transport activities of their proteins. Further studies showed that GmMOT1.1 and GmMOT1.2 improve soybean yield, especially when cultivated in acidic or slightly acidic soil. Surprisingly, these two genes contribute to soybean growth by enhancing the activity of indole-3-acetaldehyde (IAAld) aldehyde oxidase (AO), leading to increased indole-3-acetic acid (IAA) synthesis, rather than being involved in symbiotic nitrogen fixation or nitrogen assimilation. Furthermore, the geographical distribution of five haplotypes in China and their correlation with soil pH suggest the potential significance of GmMOT1.1 and GmMOT1.2 in soybean breeding strategies.


Assuntos
Molibdênio , /genética , Molibdênio/metabolismo , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Ácidos Indolacéticos/metabolismo , Solo
14.
Nat Plants ; 9(12): 1968-1977, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37932483

RESUMO

Seed plants overtook ferns to become the dominant plant group during the late Carboniferous, a period in which the climate became colder and dryer1,2. However, the specific innovations driving the success of seed plants are not clear. Here we report that the appearance of suberin lamellae (SL) contributed to the rise of seed plants. We show that the Casparian strip and SL vascular barriers evolved at different times, with the former originating in the most recent common ancestor (MRCA) of vascular plants and the latter in the MRCA of seed plants. Our results further suggest that most of the genes required for suberin formation arose through gene duplication in the MRCA of seed plants. We show that the appearance of the SL in the MRCA of seed plants enhanced drought tolerance through preventing water loss from the stele. We hypothesize that SL provide a decisive selective advantage over ferns in arid environments, resulting in the decline of ferns and the rise of gymnosperms. This study provides insights into the evolutionary success of seed plants and has implications for engineering drought-tolerant crops or fern varieties.


Assuntos
Evolução Biológica , Gleiquênias , Filogenia , Lipídeos , Gleiquênias/genética , Sementes/genética
16.
Arch. esp. urol. (Ed. impr.) ; 76(9): 690-695, 28 nov. 2023. tab, graf
Artigo em Inglês | IBECS | ID: ibc-228268

RESUMO

Background: To investigate the correlation between temperature and testicular torsion in Jiaodong Peninsula which has temperate continental monsoon climate and is represented by Yantai and its surrounding areas. Methods: A retrospective analysis was conducted by reviewing clinical data of 292 patients who were admitted and surgically confirmed to have testicular torsion in the Yantai Yuhuangding hospital medical complex between January 1, 2009, and August 31, 2022. Male patients who underwent circumcision (foreskin) were allocated to the control group. Temperature data were obtained from the China Meteorological Data Service Center. Chi-squared test or Fisher’s exact test and one-way analysis of variance were employed to compare patient characteristics and climatic variables among the different groups. Pearson’s correlation analysis was used to analyze the association between monthly average ambient temperature and monthly cumulative number of cases. Moreover, a logistic regression model was utilized to identify the independent factors of testicular torsion. Results: The mean age of patients with testicular torsion was 16.8 years. The number of cases was the highest in autumn. The temperature was the highest in summer and the lowest in winter (p < 0.01). Furthermore, the temperature difference (TD) in autumn was the highest in the four seasons groups (p < 0.01). The patients were divided into the high TD and low TD groups according to the mean TD (7.62 ◦C) on the admission day. The high TD group had a higher number of patients than the low TD group, and the temperature was lower in the former group than in the latter group (p < 0.01). A roughly negative correlation was observed between ambient temperature and the number of cases (Pearson’s r = −0.228, 95% confidence interval (CI): −0.366 to −0.079, p = 0.003) (AU)


Assuntos
Humanos , Masculino , Adolescente , Torção do Cordão Espermático/epidemiologia , Torção do Cordão Espermático/etiologia , Temperatura , Estudos Retrospectivos , Estações do Ano , China/epidemiologia
17.
J Vis Exp ; (200)2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37902337

RESUMO

Epilepsy is a neurological disorder characterized by recurrent seizures, partially correlated with genetic origin, affecting over 70 million individuals worldwide. Despite the clinical importance of epilepsy, the functional analysis of neural activity in the central nervous system is still to be developed. Recent advancements in imaging technology, in combination with stable expression of genetically encoded calcium indicators, such as GCaMP6, have revolutionized the study of epilepsy at both brain-wide and single-cell resolution levels. Drosophila melanogaster has emerged as a tool for investigating the molecular and cellular mechanisms underlying epilepsy due to its sophisticated molecular genetics and behavioral assays. In this study, we present a novel and efficient protocol for ex vivo calcium imaging in GCaMP6-expressing adult Drosophila to monitor epileptiform activities. The whole brain is prepared from cac, a well-known epilepsy gene, knockdown flies for calcium imaging with a confocal microscope to identify the neural activity as a follow-up to the bang-sensitive seizure-like behavior assay. The cac knockdown flies showed a higher rate of seizure-like behavior and abnormal calcium activities, including more large spikes and fewer small spikes than wild-type flies. The calcium activities were correlated to seizure-like behavior. This methodology serves as an efficient methodology in screening the pathogenic genes for epilepsy and exploring the potential mechanism of epilepsy at the cellular level.


Assuntos
Drosophila , Epilepsia , Animais , Humanos , Drosophila melanogaster/genética , Cálcio , Epilepsia/diagnóstico por imagem , Epilepsia/genética , Convulsões/patologia
18.
Medicine (Baltimore) ; 102(42): e35154, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37861563

RESUMO

Septic shock often occurs following critically low blood pressure in patients with sepsis, and is accompanied by a high death rate. Although mitophagy is associated with infection and immune responses, its role in septic shock remains unknown. This study screened effective mitophagy-related genes (MRGs) for medical practice and depicted immune infiltration situations in patients with septic shock. Gene expression profiles of GSE131761 from the Gene Expression Omnibus database were compiled for differential analysis, weighted gene co-expression network analysis, and immune infiltration analysis, while other GSE series were used as validation datasets. A series of validation methods were used to verify the robustness of hub genes, while a nomogram and prognosis model were established for medical practice. Six genes were screened via combinations of differentially expressed genes, weighted gene co-expression network analysis, and MRGs. From this, 3 hub genes (MAP1LC3B, ULK1, and CDC37) were chosen for subsequent analysis based on different validation methods. Gene set enrichment analysis showed that leukocyte trans-endothelial migration and the p53 signaling pathway were abnormally activated during septic shock. Immune infiltration analysis indicated that the imbalance of neutrophils and CD4 naive T cells was significantly correlated with septic shock progression. A nomogram was generated based on MAP1LC3B, ULK1, and CDC37, as well as age. The stability of our model was confirmed using a calibration plot. Importantly, patients with septic shock with the 3 highly expressed hub genes displayed worse prognosis than did patients without septic shock. MAP1LC3B, ULK1, and CDC37 are considered hub MRGs in the development of septic shock and could represent promising diagnostic and prognostic biomarkers in blood tissue. The validated hub genes and immune infiltration pattern expand our knowledge on MRG functional mechanisms, which provides guidance and direction for the development of septic shock diagnostic and therapeutic markers.


Assuntos
Sepse , Choque Séptico , Humanos , Choque Séptico/genética , Mitofagia/genética , Genes Reguladores , Linfócitos T CD4-Positivos
20.
Sci Rep ; 13(1): 17430, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37833383

RESUMO

Intestinal-type gastric adenocarcinoma (IGA) is a common phenotype of gastric cancer. Currently, few studies have constructed nomograms that may predict overall (OS) and cancer-specific survival (CSS) probability after surgery. This study is to establish novel nomograms for predicting the survival of IGA patients who received surgery. A total of 1814 IGA patients who received surgery between 2000 and 2018 were selected from Surveillance, Epidemiology, and End Results database and randomly assigned to the training and validating sets at a ratio of 7:3. Then univariate and multivariate cox regression analyses were performed to screen significant indictors for the construction of nomograms. The calibration curve, the area under the receiver operating characteristic (receiver operating characteristic, ROC) curve (the area under curve, AUC), C-index, net reclassification index (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA) curves were applied to assess the performance of the model. The significant outcomes of multivariate analysis revealed that ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, radiotherapy, number of regional nodes examined, number of regional nodes positive) were demonstrated to construct the nomogram for OS and ten variables (age, sex, race, surgery type, summary stage, grade, AJCC TNM stage, chemotherapy, number of regional nodes examined, number of regional nodes positive) for CSS. The calibration and AUC uncovered their favorable predictive performance. Subsequently, C-index, NRI, IDI and DCA curves further validated the predicative superiority of nomograms over 7th AJCC Stage System. The validated nomogram provides more reliable OS and CSS predictions for postoperative IGA patients with good accuracy, which can help surgeons in treatment decision-making and prognosis evaluation.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Nomogramas , Neoplasias Gástricas/cirurgia , Adenocarcinoma/cirurgia , Calibragem , Imunoglobulina A , Prognóstico , Programa de SEER
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