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2.
Heliyon ; 10(9): e30505, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726194

RESUMO

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

4.
Chem Biol Drug Des ; 103(4): e14519, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570708

RESUMO

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.


Assuntos
Colecistite , NF-kappa B , Humanos , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Inibidor de NF-kappaB alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Quempferóis/farmacologia , Transdução de Sinais , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Células Epiteliais/metabolismo , Sistema de Sinalização das MAP Quinases
5.
Clin Genitourin Cancer ; : 102062, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38548487

RESUMO

BACKGROUND: Although a survival benefit was observed in patients with metastatic renal cell carcinoma (mRCC) who underwent cytoreductive nephrectomy (CN), there is a lack of effective tools for predicting which individuals are likely to benefit from surgical intervention. Herein, we developed a predictive model using data from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Patients diagnosed with mRCC were screened from the SEER database (2010-2020), supplemented by patients from East Asia. Patients were categorized into surgical and non-surgical groups, with propensity score matching conducted to balance baseline characteristics. Logistic regression analysis was performed to identify independent factors associated with benefits and a nomogram was constructed based on these factors. RESULTS: This study included 11,044 cases from the SEER database and 50 cases from an external validation cohort. CN was identified as an independent protective factor for OS. A nomogram was established, and it performed well in the training and validation sets. The calibration curves and DCA confirmed that the nomogram model could precisely predict the probability of surgical benefit. We used the nomogram to classify surgical patients into benefit and non-benefit groups. Then, we found that OS was significantly higher in the benefit group than in the non-benefit group. The external validation cohort observed the same result (P=0.035). CONCLUSION: While CN offers potential benefits for patients with mRCC, its applicability varies across the patient population. Our study constructed a nomogram that quantitatively assesses the likelihood of surgical benefit in mRCC patients, facilitating more tailored therapeutic decision-making.

6.
Aging (Albany NY) ; 16(5): 4699-4722, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460946

RESUMO

BACKGROUND: Glioma is a prevalent type of malignant tumor. To date, there is a lack of literature reports that have examined the association between sulfatase modifying factor 1 (SUMF1) and glioma. METHODS: The levels of SUMF1 were examined, and their relationships with the diagnosis, prognosis, and immune microenvironment of patients with glioma were investigated. Cox and Lasso regression analysis were employed to construct nomograms and risk models associated with SUMF1. The functions and mechanisms of SUMF1 were explored and verified using gene ontology, cell counting kit-8, wound healing, western blotting, and transwell experiments. RESULTS: SUMF1 expression tended to increase in glioma tissues. SUMF1 overexpression was linked to the diagnosis of cancer, survival events, isocitrate dehydrogenase status, age, and histological subtype and was positively correlated with poor prognosis in patients with glioma. SUMF1 overexpression was an independent risk factor for poor prognosis. SUMF1-related nomograms and high-risk scores could predict the outcome of patients with glioma. SUMF1 co-expressed genes were involved in cytokine, T-cell activation, and lymphocyte proliferation. Inhibiting the expression of SUMF1 could deter the proliferation, migration, and invasion of glioma cells through epithelial mesenchymal transition. SUMF1 overexpression was significantly associated with the stromal score, immune cells (such as macrophages, neutrophils, activated dendritic cells), estimate score, immune score, and the expression of the programmed cell death 1, cytotoxic T-lymphocyte associated protein 4, CD79A and other immune cell marker. CONCLUSION: SUMF1 overexpression was found to be correlated with adverse prognosis, cancer detection, and immune status in patients with glioma. Inhibiting the expression of SUMF1 was observed to deter the proliferation, migration, and invasion of cancer cells. The nomograms and risk models associated with SUMF1 could predict the prognosis of patients with glioma.


Assuntos
Glioma , Humanos , Glioma/genética , Ativação Linfocitária , Nomogramas , Western Blotting , Contagem de Células , Prognóstico , Microambiente Tumoral/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre
7.
Zhongguo Gu Shang ; 37(3): 306-10, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38515420

RESUMO

OBJECTIVE: To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome. METHODS: From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or orthopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old. Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal. The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored. RESULTS: The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients. Chest CT showed diffuse distribution of ground glass shadows in 13 patients,and severe symptoms were "snowstorm". Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion. Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and "starry sky sign" in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex. CONCLUSION: Fat embolism syndrome has a high mortality rate. Clinical manifestations of respiratory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation. The "blizzard" sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the "starry sky" sign is the typical manifestation of diffusion-weighted sequence of brain MRI examination of fat embolism.


Assuntos
Embolia Gordurosa , Exantema , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Encéfalo , Embolia Gordurosa/diagnóstico por imagem , Embolia Gordurosa/etiologia
8.
Nat Commun ; 15(1): 40, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167292

RESUMO

The peptidyl-prolyl cis-trans isomerase Pin1 is a pivotal therapeutic target in cancers, but the regulation of Pin1 protein stability is largely unknown. High Pin1 expression is associated with SUMO1-modified protein hypersumoylation in glioma stem cells (GSCs), but the underlying mechanisms remain elusive. Here we demonstrate that Pin1 is deubiquitinated and stabilized by USP34, which promotes isomerization of the sole SUMO E2 enzyme Ubc9, leading to SUMO1-modified hypersumoylation to support GSC maintenance. Pin1 interacts with USP34, a deubiquitinase with preferential expression and oncogenic function in GSCs. Such interaction is facilitated by Plk1-mediated phosphorylation of Pin1. Disruption of USP34 or inhibition of Plk1 promotes poly-ubiquitination and degradation of Pin1. Furthermore, Pin1 isomerizes Ubc9 to upregulate Ubc9 thioester formation with SUMO1, which requires CDK1-mediated phosphorylation of Ubc9. Combined inhibition of Pin1 and CDK1 with sulfopin and RO3306 most effectively suppresses orthotopic tumor growth. Our findings provide multiple molecular targets to induce Pin1 degradation and suppress hypersumoylation for cancer treatment.


Assuntos
Glioma , Peptidilprolil Isomerase , Humanos , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Peptidilprolil Isomerase/genética , Peptidilprolil Isomerase/metabolismo , Sumoilação , Isomerismo , Fosforilação , Glioma/genética , Células-Tronco Neoplásicas/metabolismo , Proteases Específicas de Ubiquitina/metabolismo
9.
Nat Methods ; 21(1): 102-109, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37957431

RESUMO

Direct protein sequencing technologies with improved sensitivity and throughput are still needed. Here, we propose an alternative method for peptide sequencing based on enzymatic cleavage and host-guest interaction-assisted nanopore sensing. We serendipitously discovered that the identity of any proteinogenic amino acid in a particular position of a phenylalanine-containing peptide could be determined via current blockage during translocation of the peptide through α-hemolysin nanopores in the presence of cucurbit[7]uril. Building upon this, we further present a proof-of-concept demonstration of peptide sequencing by sequentially cleaving off amino acids from C terminus of a peptide with carboxypeptidases, and then determining their identities and sequence with a peptide probe in nanopore. With future optimization, our results point to a different way of nanopore-based protein sequencing.


Assuntos
Nanoporos , Peptídeos , Sequência de Aminoácidos , Proteínas Hemolisinas/química
10.
Eur J Haematol ; 112(1): 64-74, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37671595

RESUMO

OBJECTIVES: Despite the great success of CD19 CAR-T cell therapy, its clinical efficacy has been greatly hampered by the high relapse rate. In this study, we designed and compared four structures of CD19/CD22 bispecific CAR-T cells with different linkers and different orders of the antibody sequences. METHODS: We detected the cytotoxicity, cytokine secretion levels, sustainable killing ability, differentiation, exhaustion of these four CAR-T cells in vitro. The optimal Bis-C CAR-T cells were evaluated the efficacy using NSG mice. RESULTS: The two structures of CD19/CD22 bispecific CAR-T cells using (EAAAK)3 as linker had more significant cytotoxicity and cytokine secretion levels. In the process of continuous killing, Bis-C CAR-T cells showed better sustained killing ability, memory phenotype differentiation, and exhaustion. In the in vivo experiment mimicking CD19-negative relapse, Bis-C CAR-T was more able to control the tumor progression of mice in the CD19 low expression or no expression groups than CD19 CAR-T. CONCLUSIONS: This study has generated a novel bispecific CAR-T cell that can simultaneously target CD19 or CD22 positive tumor cells, providing a new strategy to address the limitations of single-targeted CAR-T therapy in B-cell tumors (limited response or relapse).


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Animais , Camundongos , Antígenos CD19 , Citocinas , Imunoterapia Adotiva , Recidiva , Linfócitos T
11.
Phytopathology ; 114(3): 618-629, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37889191

RESUMO

The dynamic of plant-parasitic nematode populations in soil is closely related to soil microorganisms. Fungi from Heterodera zeae cysts were isolated to explore the phenomenon of decline in the H. zeae population in the soil. Phylogenetic study of partial ITS, BenA, CaM, and RPB2 gene sequences, in addition to morphological investigations, was utilized to identify a nematode-destroying fungus. The nematicidal activity of a novel strain GX1 against H. zeae was assessed in vitro and in the greenhouse. Our findings revealed that strain GX1 is a new species of Talaromyces, named Talaromyces cystophila. It has a strong parasitic and lethal effect on H. zeae cysts, with 91.11% parasitism on cysts at 3 days after treatment. The contents of second-stage juveniles (J2s) and eggs inside the cysts were degraded and formed dense vacuoles, and the damaged eggs could not hatch normally. The spore suspension exhibited high nematophagous activity against nematodes, and fermentation filtrate exhibited marked inhibition of egg hatching and nematicidal activities on J2s. The hatching inhibition rates of eggs exposed to 1 × 108 CFU/ml spore suspensions or 20% 1-week fermentation filtrate (1-WF) for 15 days were 98.56 and 100%, respectively. The mortality of J2s exposed to 1 × 108 CFU/ml spore suspension reached 100% at 24 h; exposure to 50% 2-WF was 98.65 and 100% at 24 and 48 h, respectively. Greenhouse experiments revealed that the spore suspension and fermentation broth considerably decreased H. zeae reproduction by 56.17 to 78.76%. T. cystophila is a potential biocontrol strain with nematophagous and nematicidal activity that deserves attention and application.


Assuntos
Cistos , Talaromyces , Tylenchida , Tylenchoidea , Animais , Zea mays , Talaromyces/metabolismo , Filogenia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/parasitologia , Antinematódeos/farmacologia , Solo
12.
Laryngoscope ; 134(5): 2438-2443, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37991177

RESUMO

OBJECTIVES: This study evaluated the use of lidocaine spray for acute postsurgical pain control after posterior pharyngeal flap surgery. METHODS: Fifty patients aged 4 to 14 years who were scheduled to undergo elective posterior pharyngeal flap surgery were randomized to receive 2.4% lidocaine spray (Group L) or an identical volume of placebo spray (Group C) on the surgical field at the end of the surgery. The primary outcome was the maximum postoperative pain score in the postanesthesia care unit. RESULTS: The maximum pain score in Group L was significantly lower than that in Group C (p = 0.001). The incidence of moderate-to-severe pain in the postanesthesia care unit was significantly lower in Group L than that in Group C (p < 0.001). In the postanesthesia care unit, more patients in Group C were prescribed rescue analgesics (p < 0.001). The time to the first rescue analgesic was also significantly shorter in Group L (p < 0.001). The incidence and maximum score of emergence agitation were lower in Group L than in Group C. Compared with Group C, Group L showed earlier postoperative fluid intake (p = 0.001). Moreover, the score for parental satisfaction with pain control was higher in Group L than in Group C (p < 0.001). CONCLUSIONS: Our findings indicated that the use of 2.4% lidocaine aerosol spray on the surgical site at the end of the surgery could produce good analgesia for acute postoperative pain, reduce the incidence and severity of EA, and shorten the time to restore fluid intake. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2438-2443, 2024.


Assuntos
Anestésicos Locais , Lidocaína , Humanos , Analgésicos/uso terapêutico , Manejo da Dor/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Método Duplo-Cego
13.
J Laryngol Otol ; 138(4): 461-465, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38148680

RESUMO

OBJECTIVE: To analyse the comparative clinical outcomes and clinicopathological significance of vocal fold leukoplakia lesions treated by appearance classification and traditional methods. METHOD: A total of 1442 vocal fold leukoplakia patients were enrolled. Group A patients were treated according to appearance classification and Group B patients were treated according to traditional methods. RESULTS: In Group A, 24.4, 14.9 and 60.6 per cent of patients had grade I, II and III dysplasia, respectively. Grade I dysplasia (63.4 per cent) was more than twice as frequent in Group B patients than in Group A patients, while grade II dysplasia (20.4 per cent) and grade III dysplasia (16.2 per cent) were significantly less frequent in Group B patients than in Group A patients (p = 0.000). There was a significant correlation between vocal fold leukoplakia appearance and the degree of dysplasia (p = 0.000). The recurrence and malignant transformation rates (17.6 and 31 per cent, respectively) in Group B were significantly greater than those in Group A (10.8 and 25.9 per cent, respectively) (p = 0.000). CONCLUSION: Vocal fold leukoplakia appearance classification is useful for guiding treatment decision-making and could help to improve therapeutic accuracy.


Assuntos
Doenças da Laringe , Prega Vocal , Humanos , Prega Vocal/patologia , Doenças da Laringe/patologia , Leucoplasia/cirurgia , Leucoplasia/patologia
14.
Shanghai Kou Qiang Yi Xue ; 32(4): 356-362, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-38044727

RESUMO

PURPOSE: To explore the effect of sodium alginate-g-deferoxamine/chitosan (SA-g-DFO/CS) microspheres on proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). METHODS: A kind of SA-g-DFO/CS microsphere was developed through electrostatic interaction between porous chitosan microspheres and sodium alginate chemically grafted on the surface of DFO. Its morphology, porosity rate, pore size and sustained release of DFO in vitro were examined. Rat BMSCs were isolated and co-cultured with microspheres in osteogenic differentiation medium. MTT assay was used to study the influence of cell proliferation, and Calcein-AM/PI staining was used to observe the cell viability. Alkaline phosphatase (ALP) activity assay was conducted. PCR was used to detect the expression of genes related to angiogenesis and osteogenesis. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: The SA-g-DFO/CS porous microspheres were successfully prepared with a sustained re6lease of DFO. Compared with SA/CS microspheres, the SA-g-DFO/CS microspheres were conducive to cell proliferation and differentiation, with the increases in expression level of ALP, related angiogenesis genes HIF-1α, VEGF and osteogenesis genes COLI, OCN. CONCLUSIONS: The SA-g-DFO/CS porous microspheres can provide a new choice for the development of alveolar bone regeneration.


Assuntos
Quitosana , Células-Tronco Mesenquimais , Ratos , Animais , Osteogênese/genética , Desferroxamina/farmacologia , Desferroxamina/metabolismo , Microesferas , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Alginatos/farmacologia , Células Cultivadas
15.
Nat Commun ; 14(1): 6991, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914684

RESUMO

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet ß-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.


Assuntos
Hormônio Foliculoestimulante , Ilhotas Pancreáticas , Camundongos , Animais , Humanos , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/metabolismo , Secreção de Insulina , Glucose/farmacologia , Glucose/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Ilhotas Pancreáticas/metabolismo , Transdução de Sinais , Insulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Mamíferos/metabolismo
16.
Oncology ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37926087

RESUMO

BACKGROUND: Total neoadjuvant therapy (TNT) is a new strategy combining neoadjuvant therapy and chemotherapy to enhance tumor shrinkage and systemic control. Its effectiveness remains debated. OBJECTIVES: This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess TNT's impact and provide high-quality evidence for rectal cancer treatment decisions. METHOD: We searched China National Knowledge Infrastructure, VIP Database, Wanfang Database, China biomedical literature database, PubMed database, Embase database, and The Cochrane Library for RCTs comparing TNT with neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. The included trials were screened and assessed for quality based on inclusion and exclusion criteria, and meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 11 RCTs reported in 14 articles, with 1624 cases in the TNT group and 1541 cases in the CRT group. The results of the meta-analysis showed that compared with the CRT group, the TNT group had a higher pathological complete response rate (RR=1.65, 95% CI [1.40, 1.94], P<0.00001), higher T0 downstaging rate (RR=1.51, 95% CI [1.29, 1.77], P<0.00001), higher 3-year overall survival (HR=0.81, 95% CI [0.67, 0.98], P=0.03), and higher 3-year disease-free survival (HR=0.82, 95% CI [0.70, 0.95], P=0.008). However, there was no statistically significant difference between the two groups in terms of R0 resection rate (RR=1.02, 95% CI [0.99, 1.05], P=0.14), sphincter preservation rate (RR=0.94, 95% CI [0.88, 1.01], P=0.12), anastomotic leakage rate (RR=1.42, 95% CI [0.85, 2.38], P=0.18), and grade 3 or higher adverse events (RR=1.21, 95% CI [0.95, 1.54], P=0.13). CONCLUSIONS: In the treatment of locally advanced rectal cancer, TNT offers greater survival benefits compared to neoadjuvant CRT and does not significantly increase the incidence of adverse events. However, further data and studies with long-term outcomes are still required.

17.
Pestic Biochem Physiol ; 196: 105627, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37945261

RESUMO

BACKGROUND: The cap 'n' collar (Cnc) belongs to the Basic Leucine Zipper (bZIP) transcription factor super family. Cap 'n' collar isoform C (CncC) is highly conserved in the animal kingdom. CncC contributes to the regulation of growth, development, and aging and takes part in the maintenance of homeostasis and the defense against endogenous and environmental stress. Insect CncC participates in the regulation of various kinds of stress-responsive genes and is involved in the development of insecticide resistance. RESULTS: In this study, one full-length CncC sequence of Locusta migratoria was identified and characterized. Upon RNAi silencing of LmCncC, insecticide bioassays showed that LmCncC played an essential role in deltamethrin and imidacloprid susceptibility. To fully investigate the downstream genes regulated by LmCncC and further identify the LmCncC-regulated genes involved in deltamethrin and imidacloprid susceptibility, a comparative transcriptome was constructed. Thirty-five up-regulated genes and 73 down-regulated genes were screened from dsLmCncC-knockdown individuals. We selected 22 LmCncC-regulated genes and verified their gene expression levels using RT-qPCR. Finally, six LmCYP450 genes belonging to the CYP6 family were selected as candidate detoxification genes, and LmCYP6FD1 and LmCYP6FE1 were further validated as detoxification genes of insecticides via RNAi, insecticide bioassays, and metabolite identification. CONCLUSIONS: Our data suggest that the locust CncC gene is associated with deltamethrin and imidacloprid susceptibility via the regulation of LmCYP6FD1 and LmCYP6FE1, respectively.


Assuntos
Inseticidas , Locusta migratoria , Humanos , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Locusta migratoria/genética , Locusta migratoria/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
18.
Nat Prod Res ; : 1-5, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752711

RESUMO

Two new C-glucofuranosyl flavones apigenin 6-C-ß-glucofuranoside (1) and apigenin 6-C-α-glucofuranoside (2) together with four known compounds (3-6) were isolated from the flowers of Gypsophila oldhamiana. Their structures were elucidated on the basis of extensive spectroscopic analyses. These compounds were evaluated for the cytotoxic activities against four human cancer cell lines and did not exhibit any significant bioactivities (IC50 values > 10 µM).

19.
Am J Reprod Immunol ; 90(4): e13774, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37766404

RESUMO

PROBLEM: We aimed to explore the risk factors in patients with unexplained recurrent spontaneous abortion (URSA) and to provide a basis for clinically targeted therapy. METHOD OF STUDY: This case-control study comprised 202 patients with URSA treated at our hospital and 115 women in early pregnancy with a normal birth history during the same period. After procuring the data we conducted a multivariate logistic regression analysis of risk factors related to URSA. RESULTS: Logistic regression analysis showed (i) that the number of spontaneous abortions (SAs; odds ratio [OR] = 492.123), the levels of autoantibodies (OR = 19.322) and tumor necrosis factor alpha (TNF-α; OR = 9.615), and the CT and TT genotypes of methylenetetrahydrofolate reductase (MTHFR) C677T (OR = 6.217 and 15.009, respectively) were risk factors for URSA and (ii) that 25-hydroxyvitamin D (25-(OH)D; OR = 0.919) was a protective factor. The most important risk factor was a history of one or more SAs, with the risk of pregnancy loss increasing 491.123-fold. Every unit increase in serum 25-(OH)D reduced the risk of SA by 8.1%. CONCLUSIONS: The risk factors for URSA included the number of SAs, the levels of autoantibodies and TNF-α, and the MTHFR C677T T allele; 25-(OH)D was a protective factor. We recommend that women diagnosed with URSA receive intervention as soon as possible so as to actively reduce the incidence of recurrent SA.

20.
Zhongguo Zhen Jiu ; 43(8): 916-20, 2023 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-37577888

RESUMO

OBJECTIVE: To observe the effect of Dong's extraordinary point needling technique on postoperative complications of anal fistula. METHODS: A total of 241 patients undergoing anal fistula surgery were randomly divided into an observation group (121 cases, 3 cases dropped off) and a control group (120 cases, 2 cases dropped off). The patients in the control group were treated with intramuscular injection of compound diclofenac sodium injection and oral administration of tamsulosin hydrochloride sustained release capsules. In addition to the treatment in the control group, the patients in the observation group were treated with Daoma needling technique at the "Sanqi points" (Qimen point, Qijiao point, and Qizheng point) combined with Dongqi needling technique at "Sanhuang points" (sub-Tianhuang point, Dihuang point, Renhuang point), with each session lasting 30 min. The treatment in the two groups both started on the first day after surgery, and was given once daily for 14 consecutive days. Visual analog scale (VAS) score was compared between the two groups on postoperative day 1, 7, and 14; bladder residual urine volume, spontaneous voiding volume, and urinary catheterization frequency were assessed after treatment on postoperative day 1; and anorectal dynamic indexes (anal canal resting pressure, rectal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold) were evaluated before surgery and on postoperative day 4. Clinical efficacy was assessed in both groups one month after surgery. RESULTS: On postoperative day 7 and 14, the VAS scores of both groups were lower than those on postoperative day 1 (P<0.05), and the VAS scores in the observation group were lower than those in the control group (P<0.05). The bladder residual urine volume and urinary catheterization frequency in the observation group were lower than those in the control group (P<0.05), while the spontaneous voiding volume was higher than that in the control group (P<0.05). On postoperative day 4, the anal canal resting pressure, maximum squeeze pressure of the anal canal, and the minimum rectal sensory threshold were lower than preoperative values (P<0.05), while the rectal resting pressure was higher than preoperative value (P<0.05) in both groups. The anal canal resting pressure, maximum squeeze pressure of the anal canal, and minimum rectal sensory threshold were lower than those in the control group, and the rectal resting pressure was higher than that in the control group (P<0.05). The effective rate was 93.2% (110/118) in the observation group, which was higher than 84.7% (100/118) in the control group (P<0.05). CONCLUSION: Dong's extraordinary point needling technique could reduce postoperative pain, alleviate urinary retention, and improve defecation in patients undergoing anal fistula surgery.


Assuntos
Doenças do Ânus , Fístula Retal , Humanos , Reto , Fístula Retal/etiologia , Fístula Retal/cirurgia , Canal Anal/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Pontos de Acupuntura
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