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1.
Front Oncol ; 14: 1371878, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585011

RESUMO

Purpose: This study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC). Methods and materials: Our retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a "MELODIE" multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed. Results: After a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects. Conclusion: Long-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.

2.
BMC Plant Biol ; 24(1): 255, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594641

RESUMO

BACKGROUND: Orchidaceae is one of the largest groups of angiosperms, and most species have high economic value and scientific research value due to their ornamental and medicinal properties. In China, Chinese Cymbidium is a popular ornamental orchid with high economic value and a long history. However, to date, no detailed information on the mitochondrial genome of any species of Chinese Cymbidium has been published. RESULTS: Here, we present the complete assembly and annotation of the mitochondrial genome of Cymbidium ensifolium (L.) Sw. The mitogenome of C. ensifolium was 560,647 bp in length and consisted of 19 circular subgenomes ranging in size from 21,995 bp to 48,212 bp. The genome encoded 35 protein-coding genes, 36 tRNAs, 3 rRNAs, and 3405 ORFs. Repeat sequence analysis and prediction of RNA editing sites revealed a total of 915 dispersed repeats, 162 simple repeats, 45 tandem repeats, and 530 RNA editing sites. Analysis of codon usage showed a preference for codons ending in A/T. Interorganellar DNA transfer was identified in 13 of the 19 chromosomes, with plastid-derived DNA fragments representing 6.81% of the C. ensifolium mitochondrial genome. The homologous fragments of the mitochondrial genome and nuclear genome were also analysed. Comparative analysis showed that the GC content was conserved, but the size, structure, and gene content of the mitogenomes varied greatly among plants with multichromosomal mitogenome structure. Phylogenetic analysis based on the mitogenomes reflected the evolutionary and taxonomic statuses of C. ensifolium. Interestingly, compared with the mitogenomes of Cymbidium lancifolium Hook. and Cymbidium macrorhizon Lindl., the mitogenome of C. ensifolium lost 8 ribosomal protein-coding genes. CONCLUSION: In this study, we assembled and annotated the mitogenome of C. ensifolium and compared it with the mitogenomes of other Liliidae and plants with multichromosomal mitogenome structures. Our findings enrich the mitochondrial genome database of orchid plants and reveal the rapid structural evolution of Cymbidium mitochondrial genomes, highlighting the potential for mitochondrial genes to help decipher plant evolutionary history.


Assuntos
Genoma Mitocondrial , Orchidaceae , Genoma Mitocondrial/genética , Filogenia , Mitocôndrias/genética , DNA , Orchidaceae/genética
3.
Orphanet J Rare Dis ; 19(1): 160, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609989

RESUMO

BACKGROUND: Primary periodic paralysis (PPP) is an inherited disorders of ion channel dysfunction characterized by recurrent episodes of flaccid muscle weakness, which can classified as hypokalemic (HypoPP), normokalemic (NormoPP), or hyperkalemic (HyperPP) according to the potassium level during the paralytic attacks. However, PPP is charactered by remarkable clinical and genetic heterogeneity, and the diagnosis of suspected patients is based on the characteristic clinical presentation then confirmed by genetic testing. At present, there are only limited cohort studies on PPP in the Chinese population. RESULTS: We included 37 patients with a clinical diagnosis of PPP. Eleven (29.7%) patients were tested using a specific gene panel and 26 (70.3%) by the whole-exome sequencing (WES). Twenty-two cases had a genetic variant identified, representing a diagnostic rate of 59.5% (22/37). All the identified mutations were either in the SCN4A or the CACNA1S gene. The overall detection rate was comparable between the panel (54.5%: 6/11) and WES (61.5%: 16/26). The remaining patients unresolved through panel sequencing were further analyzed by WES, without the detection of any mutation. The novel atypical splicing variant c.2020-5G > A affects the normal splicing of the SCN4A mRNA, which was confirmed by minigene splicing assay. Among 21 patients with HypoPP, 15 patients were classified as HypoPP-2 with SCN4A variants, and 6 HypoPP-1 patients had CACNA1S variants. CONCLUSIONS: Our results suggest that SCN4A alleles are the main cause in our cohort, with the remainder caused by CACNA1S alleles, which are the predominant cause in Europe and the United States. Additionally, this study identified 3 novel SCN4A and 2 novel CACNA1S variants, broadening the mutation spectrum of genes associated with PPP.


Assuntos
Paralisia Periódica Hipopotassêmica , Distrofias Musculares , Humanos , Paralisia Periódica Hipopotassêmica/genética , Alelos , Paralisia , China , Canal de Sódio Disparado por Voltagem NAV1.4/genética
4.
Oral Oncol ; 152: 106798, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615583

RESUMO

Acquired radio-resistance is thought to be one of the main causes of recurrent metastasis after failure of nasopharyngeal carcinoma (NPC) radiotherapy, which may be related to X-ray-induced epithelial-mesenchymal transition (EMT) activation. The circadian clock gene, BMAL1, has been shown to correlate with the sensitivity of NPCs to radiotherapy, but the specific mechanism has not been reported. NPC cells were irradiated by conventional fractionation to generate radiotherapy-resistant cells. NPC cells with BMAL1 gene stabilization/overexpression and interference were obtained by lentiviral transfection. Western blotting, colony formation analysis, cell counting kit-8 assays, wound-healing tests, Transwell assays, flow cytometry, the EDU method, nuclear plasma separation experiments, HE staining, immunohistochemical staining and TUNEL staining were performed to explore the influence and molecular mechanism of the circadian clock gene, BMAL1, on NPC-acquired radio-resistance and EMT through in vitro and in vivo experiments. The results indicated that there was a gradual downregulation of BMAL1 gene protein expression during the routine dose induction of radio-resistance in NPC cells. EMT activation was present in the radiation-resistant cell line 5-8FR, and was accompanied by the significant enhancement of proliferation, migration and invasion. The BMAL1 gene significantly increased the radiosensitivity of the radiation-resistant cell line 5-8FR and reversed the acquired radio-resistance of NPCs, which was accomplished by inhibiting the TGF-ß1/Smads/Snail1 axis-mediated EMT.

5.
Proc (Bayl Univ Med Cent) ; 37(3): 403-407, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628324

RESUMO

Background: Diagnosing atypical glandular cells (AGC) is a significant challenge in cytomorphology. Methods: A retrospective study was undertaken to assess the prevalence of AGC and the subsequent histological outcomes over 5 years at a single institution. Results: A total of 159,649 ThinPrep Pap tests, including 395 cases of AGC, were retrieved, of which 330 AGC cases had follow-up histopathology. Among these 330 cases, 43.9% were classified as AGC not otherwise specified, followed by AGC-endocervical cells at 33.3%. The most frequently observed histological findings at follow-up included CIN1 and benign mucosa with reactive changes, followed by high-grade squamous intraepithelial lesion and cervical squamous cell carcinoma. The overall 5-year insignificant AGC rate was 0.12%, and the overall 5-year significant AGC rate was 0.08%. Notably, 36.7% of AGC cases tested positive for high-risk human papillomavirus. Interestingly, the level of experience did not significantly impact the rates for significant or insignificant AGC diagnosis. However, senior cytopathologists had a higher AGC report rate compared to their junior peers. Conclusion: The AGC diagnostic rate at our institution falls within the range given by the College of American Pathologists. A significant number of cases had follow-up histologic results available, and the overall 5-year insignificant AGC rate was 0.12%.

6.
Front Pediatr ; 12: 1378786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590767

RESUMO

Background: Enhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD. Methods: A prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate. Results: A total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups. Conclusions: In this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.

7.
J Chem Phys ; 160(14)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38587221

RESUMO

Transition metal catalysts supported on topological insulators are predicted to show improved catalytic properties due to the presence of topological surface states, which may float up to the catalysts and provide robust electron transfer. However, experimental studies of surface structures and corresponding catalytic properties of transition metal/topological insulator heterostructures have not been demonstrated so far. Here, we report the structures, chemical states, and adsorption behaviors of two conventional transition metal catalysts, Pt and Pd, on the surface of Bi2Se3, a common topological insulator material. We reveal that Pt forms nanoparticles on the Bi2Se3 surface. Moreover, the interaction between Pt and surface Se is observed. Furthermore, thermal dosing of O2 onto the Pt/Bi2Se3 heterostructure leads to no oxygen adsorption. Detailed scanning tunneling microscopy study indicates that Pt transforms into PtSe2 after the thermal process, thus preventing O2 from adsorption. For another transition metal Pd, it exhibits approximate layer-island growth on Bi2Se3, and Pd-Se interaction is also observed. Our work provides significant insights into the behaviors of transition metals on top of a common topological insulator material and will assist in the future design of catalysts built with topological materials.

8.
J Clin Lab Anal ; 38(6): e25028, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506373

RESUMO

OBJECTIVE: The objective of the study was to validate the dissociation phenomenon of erythrocyte agglutination which is based on erythrocyte fragments and to apply it in the functional activity assay of the complement system. METHODS: The dissociation-agglutination effect of erythrocyte fragments was validated by detecting the number of free erythrocytes after the action of erythrocyte fragments on agglutinated erythrocytes. The number of free erythrocytes produced after hemolysis of agglutinated erythrocytes caused by complements and complement activators(CAs) was detected by auto hematology analyzer and the results were indicated by mean hemoglobin concentration of erythrocytes (MCHC). We optimized the test conditions and validated the inter-batch stability, explored the resolution of the assay method, and assayed for the total complement activity (AC) and the CAs activated complement activity (ACA) in serum from patients and healthy individual groups. RESULTS: Erythrocyte fragments have a dissociative effect on agglutinated erythrocytes. The auto hematology analyzer was able to detect AC and ACA, where AC showed an inverse correlation with MCHC, and ACA demonstrated a positive correlation with MCHC. The inter-batch CV of AC, ACA, and ACA/AC was found to be 5%, 9%, and 11.7%, respectively, with good stability. The study found that serum samples from acute phase reaction patients showed significant differences in ACA compared with healthy individuals, with a p value of 0.018; serum samples from patients with nephrotic syndrome showed significant differences in AC, ACA, and ACA/AC compared with healthy individuals, with p values of 0.014, 0.002, and 0.041, respectively. CONCLUSION: Erythrocyte fragments have dissociation-agglutination effect. The complement system immunological functional detection method, based on this effect, has potential clinical application value due to its sensitivity and accuracy.


Assuntos
Eritrócitos , Laboratórios Clínicos , Humanos , Proteínas do Sistema Complemento , Hemólise , Aglutinação
9.
Environ Res ; 251(Pt 2): 118661, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490628

RESUMO

Climate change is a common challenge faced by all humanity. Promoting emission and carbon reduction in agricultural land is the most important priority for addressing climate change and realizing sustainable development. Based on data from 296 prefecture-level cities in China from 2011 to 2021, this study utilizes machine-learning and text-analysis methods to construct an indicator of government climate-risk attention (GCRA). It combines a two-way fixed-effects model to investigate how GCRA affects agricultural-land carbon emissions (ALCE) and carbon intensity (ALCI) and the mechanism of the impact. The results indicate that (1) GCRA substantially reduces ALCE and ALCI, and the conclusions are robust to a battery of tests. Furthermore, (2) mechanism analysis reveals that GCRA primarily uses three mechanisms-strengthening environmental regulation, promoting agricultural green-technology innovation, and upgrading agricultural-land mechanization-to reduce ALCE and lower ALCI. Additionally, (3) heterogeneity analysis suggests that the carbon-emission reduction effect of GCRA is more significant in the east, in arid and humid climate zones, and in non-grain-producing regions. Finally, (4) spatial-spillover effect analysis and quantile regression results demonstrate that GCRA also significantly inhibits carbon emissions and the carbon intensity of nearby agricultural land, with the inhibition effect becoming more pronounced at higher levels of government attention. This study's discoveries are helpful in promoting the emission reduction and carbon sequestration of agricultural land and provide references for developing countries to cope with climate change.

10.
Microbiol Spectr ; 12(4): e0347723, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38456681

RESUMO

Canine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine. IMPORTANCE: Many sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.


Assuntos
Vírus da Cinomose Canina , Vacinas Virais , Cães , Animais , Camundongos , Vírus da Cinomose Canina/genética , Vacinas Virais/genética , Linfócitos T CD8-Positivos , Anticorpos Antivirais , Proteínas Recombinantes , Vacinas de Subunidades/genética
11.
iScience ; 27(4): 109372, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38510114

RESUMO

In the tumor microenvironment (TME), tumor-associated NEs (TANs) have the potential to be protumorigenic or antitumorigenic within the TME in response to environmental cues. The diversity and plasticity of NEs (NEs) underlie the dual potential of TANs in the TME. Here, we utilized the tumor-targeting bacterium VNP20009 (VNP) to carry a plasmid expressed IFNß (VNP-IFNß), which can deliver IFNß and remodel TANs to an antitumorigenic phenotype, and performed preclinical evaluations in the B16F10 lung metastasis model and the B16F10 subcutaneous xenograft model. Compared with VNP, VNP-IFNß recruited more NEs and macrophages (Mφs) with antitumor phenotypes in lung metastases and activated dendritic cells (DCs) differentiation, which activated antitumor immune responses of CD4+ T cells, and ultimately inhibited melanoma progression. This study enriches the bacterial-mediated tumor therapy by using tumor-targeting bacteria to deliver IFNß to the tumor site and inhibit melanoma growth and metastasis by remodeling the tumor immune microenvironment.

12.
J Integr Neurosci ; 23(3): 52, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38538217

RESUMO

BACKGROUND: A hospital-based case-control study was carried out to elucidate the association of Matrix metalloproteinase-2 (MMP-2) gene candidate polymorphisms with the susceptibility to Alzheimer's disease (AD) in the Chinese Han population. METHODS: A total of 200 AD cases and an equal number of healthy controls were recruited to undergo genotyping of specific loci within the MMP-2 gene loci (rs243866, rs2285053, rs243865). Logistic regression analysis was applied to examine the association of the genotypes and alleles of MMP-2 gene polymorphisms with AD after adjusting clinical confounding factors. RESULTS: Within AD group, a high proportion of rs243866 genotype carriers were found, and the difference remained significant despite adjusting for other clinical indicators. Among individuals with the rs243866 AA genotype and rs243865 TT genotype, the onset age of AD occurred at a younger age. Early-onset AD risk in rs243866 AA genotype carriers was 6.528 times higher than those in GG genotype carriers, and individuals with rs243865 TT genotype faced a 4.048-fold increased risk compared to those with CC genotype. CONCLUSIONS: MMP-2 gene rs243866 and rs243865 polymorphisms were closely associated with the onset age of AD. The presence of rs243866 AA genotype emerged as a crucial predictor of AD risk.


Assuntos
Doença de Alzheimer , Metaloproteinase 2 da Matriz , Humanos , Metaloproteinase 2 da Matriz/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Doença de Alzheimer/genética , Polimorfismo de Nucleotídeo Único
13.
Microbiol Resour Announc ; 13(4): e0001124, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38441027

RESUMO

Kluyvera ascorbata is recognized as an opportunistic pathogen of the Enterobacteriaceae family but remains less studied. We report the draft genome of a K. ascorbata clinical strain recovered from human sputum, comprising approximately 5.18 million bases and harboring an intrinsic gene encoding the extended-spectrum ß-lactamase CTX-M-270.

14.
Clin. transl. oncol. (Print) ; 26(3): 747-755, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230804

RESUMO

Background This review was implemented to examine the impact of bone metastasis on the prognosis of non-small cell lung cancer patients (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods A literature search was conducted in the PubMed, CENTRAL, Web of Science, and Embase databases up to 4th September 2022. Multivariable adjusted data were pooled in a random-effects model. Results 13 studies were included. On a combined analysis of 10 studies, it was noted that bony metastasis was associated with poor overall survival (OS) in NSCLC patients treated with ICIs (HR: 1.55 95% CI 1.24, 1.94 I2 = 69% p = 0.001). Meta-analysis of seven studies showed that bony metastasis was not associated with poor progression-free survival (PFS) in NSCLC patients treated with ICIs (HR: 1.31 95% CI 0.85, 2.01 I2 = 85% p = 0.22). Meta-regression analysis using the moderator's age, male gender, smoking history, squamous histology, and ICI as 1st line therapy for the outcome OS was not statistically significant. Conclusion The presence of bone metastasis is a predictor of poor OS in NSCLC treated with ICIs. However, PFS does not seem to be influenced by the presence of bone metastasis. Clinicians should prioritize the management of NSCLC patients with bone metastasis and explore the use of combination therapies to achieve optimal results. Further studies taking into account different combination therapies for such patients would strengthen the evidence (AU)


Assuntos
Humanos , Masculino , /uso terapêutico , Neoplasias de Tecido Ósseo/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico
15.
Exp Ther Med ; 27(4): 149, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476918

RESUMO

V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) encodes a serine-threonine kinase. The V600E point mutation in the BRAF gene is the most common mutation, predominantly occurring in melanoma, and colorectal, thyroid and non-small cell lung cancer. Particularly in the context of thyroid cancer research, it is routinely employed as a molecular biomarker to assist in diagnosing and predicting the prognosis of papillary thyroid cancer (PTC), and to formulate targeted therapeutic strategies. Currently, several methods are utilized in clinical settings to detect BRAF V600E mutations in patients with PTC. However, the sensitivity and specificity of various detection techniques vary significantly, resulting in diverse detection outcomes. The present review highlights the advantages and disadvantages of the methods currently employed in medical practice, with the aim of guiding clinicians and researchers in selecting the most suitable detection approach for its high sensitivity, reproducibility and potential to develop targeted therapeutic regimens for patients with BRAF gene mutation-associated PTC.

16.
J Nanobiotechnology ; 22(1): 69, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369519

RESUMO

BACKGROUND: Neutrophil extracellular traps (NETs), antibacterial weapons of neutrophils (NEs), have been found to play a crucial role in cancer metastasis in recent years. More and more cancer research is focusing on anti-NETs. However, almost all anti-NETs treatments have limitations such as large side effects and limited efficacy. Therefore, exploring new anti-NETs therapeutic strategies is a long-term goal. RESULTS: The transmembrane protein coiled-coil domain containing 25 (CCDC25) on tumor cell membranes can bind NETs-DNA with high specificity and affinity, enabling tumor cells to sense NETs and thus promote distant metastasis. We transformed shCCDC25 into VNP20009 (VNP), an oncolytic bacterium, to generate VNP-shCCDC25 and performed preclinical evaluation of the inhibitory effect of shCCDC25 on cancer metastasis in B16F10 lung metastasis and 4T1 orthotopic lung metastasis models. VNP-shCCDC25 effectively blocked the downstream prometastatic signaling pathway of CCDC25 at tumor sites and reduced the formation of NETs while recruiting more neutrophils and macrophages to the tumor core, ultimately leading to excellent metastasis inhibition in the two lung metastasis models. CONCLUSION: This study is a pioneer in focusing on the effect of anti-NET treatment on CCDC25. shCCDC25 is effectively delivered to tumor sites via the help of oncolytic bacteria and has broad application in the inhibition of cancer metastasis via anti-NETs.


Assuntos
Armadilhas Extracelulares , Neoplasias Pulmonares , Ácidos Nucleicos , Humanos , Armadilhas Extracelulares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neutrófilos/metabolismo , Ácidos Nucleicos/uso terapêutico
17.
Int J Biol Macromol ; 262(Pt 1): 129806, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325693

RESUMO

Emulsion gels with denser network microstructure and stronger mechanical properties have attracted increasing attentions for delivering lipophilic compounds. In this study, the effect of three distinct soluble dietary fiber (inulin (IN), resistant dextrin (RD) and stachyose (ST)) on the rheological, mechanical and microstructural properties of soy protein isolate (SPI) emulsion gel were firstly investigated. Compared with RD and IN, ST significantly accelerated water holding capacity and thermal stability, which exhibited more compact microstructure and more uniform emulsified oil droplets. Subsequently, the stability and bioavailability of vitamin D3 (VD3) in different delivery systems (medium chain triglycerides (MCT) embedding, SPI-ST emulsion embedding, SPI emulsion gel embedding and SPI-ST emulsion gel embedding) were continue evaluated. In vitro simulated digestion experiment demonstrated that the bioaccessibility of encapsulated VD3 in SPI-ST emulsion gel (69.95 %) was much higher than that of free embedding (48.99 %). In vivo pharmacokinetic experiment revealed that the bioavailability of VD3 was significantly enhanced in SPI-ST gel (p < 0.05), with the AUC0-24h value of 25-OH VD3 (the main circulating form of VD3) were 1.34-fold, 1.23-fold higher than that of free embedding, MCT embedding, respectively. These findings provide a possible approach for the development of high protein/fiber functional foods containing enhanced hydrophobic bioactives.


Assuntos
Colecalciferol , Proteínas de Soja , Emulsões/química , Proteínas de Soja/química , Inulina , Fibras na Dieta , Géis/química
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(2): 193-198, 2024 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-38311558

RESUMO

OBJECTIVE: To explore the genetic etiology of a child with delayed growth and development and carry out a literature review. METHODS: A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy. RESULTS: The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR-agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion. CONCLUSION: The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.


Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Criança , Feminino , Humanos , Masculino , Gravidez , Quinases Ciclina-Dependentes/genética , Éxons , Homozigoto , Deleção de Sequência
19.
Aging (Albany NY) ; 16(4): 3837-3855, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38376441

RESUMO

Immunotherapy is currently one of the most viable therapies for head and neck squamous cell carcinoma (HNSCC), characterized by high immune cell infiltration. The Wnt-signaling inhibitor and immune activation mediator, Dickkopf-1 (DKK1), has a strong correlation with tumor growth, tumor microenvironment, and, consequently, disease prognosis. Nevertheless, it is still unclear how DKK1 expression, HNSCC prognosis, and tumor-infiltrating lymphocytes are related. To better understand these associations, we examined how DKK1 expression varies across different tumor and normal tissues. In our study, we investigated the association between DKK1 mRNA expression and clinical outcomes. Next, we assessed the link between DKK1 expression and tumor immune cell infiltration. Additionally, using immunohistochemistry, we evaluated the expression of DKK1 in 15 healthy head and neck tissue samples, and the expression of CD3, CD4, and DKK1 in 27 HNSCC samples. We also explored aberrant DKK1 expression during tumorigenesis. DKK1 expression was remarkably higher in HNSCC tissues than in healthy tissues, and was shown to be associated with tumor stage, grade, lymph node metastasis, histology, and a dismal clinical prognosis in HNSCC. DKK1 expression in HNSCC tissues was inversely correlated with CD3+ (P < 0.0001) and CD4+ (P < 0.0001) immune cell infiltration, while that in immune cells was inversely associated with HNSCC prognosis. These findings offer a bioinformatics perspective on the function of DKK1 in HNSCC immunotherapy and provide justification for clinical research on DKK1-targeted HNSCC treatments. DKK1 is a central target for improving the efficacy of HNSCC immunotherapy.


Assuntos
Carcinogênese , Neoplasias de Cabeça e Pescoço , Humanos , Biomarcadores , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral
20.
Langmuir ; 40(10): 5326-5337, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38408337

RESUMO

Capacitors with zinc ions, with excellent stabilities, low cost, and high energy density, are expected to be promising energy storage devices. However, the development of zinc-ion capacitors is quietly restricted by low specific capacity and cycling stability. Herein, to overcome these limitations, honeycomb-structured S, N-codoped carbon (SNPC) is constructed by one-pot calcination of waste corn bracts and thiourea. The honeycomb structure of SNPC is demonstrated to provide abundant active sites that can enhance the extron/ion transport, conductivity for high power export, and ion adsorption capacity in energy storage applications, leading to a higher electrochemical performance achieved. The electrolytes of zinc salt have also been studied. It reveals that the SNPC electrode presents the best electrochemical performance in a 2 M ZnSO4 and 0.5 M ZnCl2 electrolyte mixture because in the electrolyte mixture, Cl- can replace the existing bound water in the solvation structure to form an anion-type water-free solvation structure ZnCl42-. The SNPC-800 electrode with a highly improved surface area (∼909.0 m2 g-1) is proved to be more suitable as the electrode than other materials. Aqueous zinc-ion capacitors (ZICs) have been assembled by the honeycomb-structured SNPC-800 as the cathode, which can achieve a relatively wide working voltage range of 0.1-1.8 V. The SNPC-800 ZICs exhibit a superior specific capacity of 179.1 mA h g-1 at 0.1 A g-1. The energy density of SNPC-800 ZICs reaches an impressive value of 89.6 Wh kg-1 at 53.8 W kg-1, and it sustains 28.3 Wh kg-1 at 1997.6 W kg-1. In addition, there is 99.8% capacity retention in the SNPC-800 ZICs over 5000 cycles. The absorption energy in SPNC is much higher than that in undoped CPC, as confirmed by density functional theory, which reveals that introducing of heteroatoms (S, N) has a comparatively active advantage at increasing the Zn-ion storage capacity. This work proposes a practical strategy for the effective recycling of waste biomass materials into honeycomb carbon electrode materials. Moreover, the honeycomb carbon-based ZICs with excellent electrochemical performance and long-term cycling stability possess great potential to be a superior cathode in practical applications.

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