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1.
Nat Commun ; 15(1): 3396, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649355

RESUMO

The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

2.
Biochem Biophys Res Commun ; 710: 149895, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38593620

RESUMO

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.


Assuntos
Antineoplásicos , Ferroptose , Furanos , Lignanas , Síndromes Neurotóxicas , Humanos , Cisteína , Cistina , Fluoruracila , Antineoplásicos/farmacologia , Sistema y+ de Transporte de Aminoácidos
3.
Chemistry ; : e202400348, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602023

RESUMO

Utilizing photocatalytic method to produce hydrogen by splitting water is an efficient strategy to solve the hotspot issues of energy crisis and environmental pollution. Herein, we systematically investigate the corresponding properties of the reported Cu-bearing ternary compound monolayer CuP2Se by using the first-principle calculations. The monolayer CuP2Se has quite small cleavage energy of 0.51 J/m2, indicating it can be easily produced by the mechanical exfoliation method experimentally. In addition, it is an indirect bandgap semiconductor material which has a moderate value of 1.91 eV. The conduction band minimum (CBM) and valence band maximum (VBM) can perfectly straddle the redox potentials of water when a biaxial strain of -4% to 4% is applied, unveiling the high photocatalytic thermodynamic stability of monolayer CuP2Se in response to the effect of solvent tension. Remarkably, the monolayer CuP2Se also demonstrates significant sunlight capturing ability in the visible region. The outstanding electronic and optical properties suggest that the monolayer CuP2Se is undoubtedly a viable material for photocatalytic water splitting.

4.
J Fluoresc ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602590

RESUMO

In the present research, novel lanthanide coordination compounds [DyL(PhCOO)(CH3OH)](ClO4)2·(CH3OH)2 (1) were characterized by the compression of 2,6-diformyl-4-methyl-phenol (dmp) and 1,3-diamino-2-propanol using benzoate as the secondary ligand, where L indicates the deprotonated macrocyclic ligand. Through the high structural rigidity driven by the coordination of the macrocyclic ligand formed by condensation in methanol solution and sodium benzoate with Dy(ClO4)3·6H2O, compound 1 exhibits outstanding cyan-emitting fluorescence performance and potential applications as a fluorescent material. Additionally, hyaluronic acid (HA)/ carboxymethyl chitosan (CMCS) hydrogels were prepared with loaded resveratrol metal-organic complexes according to the synthetic chemical approach. In biological study, we evaluated the effect of hydrogels on oxidative stress on human dermal fibroblasts. Examined by molecular docking simulation, the results showed that the binding interactions were from the phenol group, the carboxyl group and also the "-N=" group, indicating Dy metal complex has excellent biological capability.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38593466

RESUMO

The global annual vegetable and fruit waste accounts for more than one-fifth of food waste, mainly due to deterioration. In addition, agricultural product spoilage can produce foodborne illnesses and threaten public health. Eco-friendly preservation technologies for extending the shelf life of agricultural products are of great significance to socio-economic development. Here, we report a dual-functional TENG (DF-TENG) that can simultaneously prolong the storage period of vegetables and realize wireless storage condition monitoring by harvesting the rotational energy. Under the illumination of the self-powered high-voltage electric field, the deterioration of vegetables can be effectively slowed down. It can not only decrease the respiration rate and weight loss of pakchoi but also increase the chlorophyll levels (∼33.1%) and superoxide dismutase activity (∼11.1%) after preservation for 4 days. Meanwhile, by harvesting the rotational energy, the DF-TENG can be used to drive wireless sensors for monitoring the storage conditions and location information of vegetables during transportation in real time. This work provides a new direction for self-powered systems in cost-effective and eco-friendly agricultural product preservation, which may have far-reaching significance to the construction of a sustainable society for reducing food waste.

6.
Front Optoelectron ; 17(1): 9, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584213

RESUMO

This paper presents an efficient scheme for single-pixel imaging (SPI) utilizing a phase-controlled fiber laser array and an untrained deep neural network. The fiber lasers are arranged in a compact hexagonal structure and coherently combined to generate illuminating light fields. Through the utilization of high-speed electro-optic modulators in each individual fiber laser module, the randomly modulated fiber laser array enables rapid speckle projection onto the object of interest. Furthermore, the untrained deep neural network is incorporated into the image reconstructing process to enhance the quality of the reconstructed images. Through simulations and experiments, we validate the feasibility of the proposed method and successfully achieve high-quality SPI utilizing the coherent fiber laser array at a sampling ratio of 1.6%. Given its potential for high emitting power and rapid modulation, the SPI scheme based on the fiber laser array holds promise for broad applications in remote sensing and other applicable fields.

7.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473706

RESUMO

Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.


Assuntos
Injúria Renal Aguda , Animais , Camundongos , Flavonoides , Técnicas de Cultura de Células , Ácido Fólico
8.
Sci Adv ; 10(13): eadi9035, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552007

RESUMO

The pharyngeal endoderm, an innovation of deuterostome ancestors, contributes to pharyngeal development by influencing the patterning and differentiation of pharyngeal structures in vertebrates; however, the evolutionary origin of the pharyngeal organs in vertebrates is largely unknown. The endostyle, a distinct pharyngeal organ exclusively present in basal chordates, represents a good model for understanding pharyngeal organ origins. Using Stereo-seq and single-cell RNA sequencing, we constructed aspatially resolved single-cell atlas for the endostyle of the ascidian Styela clava. We determined the cell composition of the hemolymphoid region, which illuminates a mixed ancestral structure for the blood and lymphoid system. In addition, we discovered a cluster of hair cell-like cells in zone 3, which has transcriptomic similarity with the hair cells of the vertebrate acoustico-lateralis system. These findings reshape our understanding of the pharynx of the basal chordate and provide insights into the evolutionary origin of multiplexed pharyngeal organs.


Assuntos
Urocordados , Animais , Urocordados/genética , Faringe , Vertebrados , Evolução Biológica , Diferenciação Celular
9.
J Affect Disord ; 355: 190-199, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38548195

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is an immune-mediated and multi-systemic disease which may affect the nervous system, causing neuropsychiatric SLE (NPSLE). Recent neuroimaging studies have examined brain functional alterations in SLE. However, discrepant findings were reported. This meta-analysis aims to identify consistent resting-state functional abnormalities in SLE. METHODS: PubMed and Web of Science were searched to identify candidate resting-state functional MRI studies assessing SLE. A voxel-based meta-analysis was performed using the anisotropic effect-size version of the seed-based d mapping (AES-SDM). The abnormal intrinsic functional patterns extracted from SDM were mapped onto the brain functional network atlas to determine brain abnormalities at a network level. RESULTS: Twelve studies evaluating fifteen datasets were included in this meta-analysis, comprising 572 SLE patients and 436 healthy controls (HCs). Compared with HCs, SLE patients showed increased brain activity in the bilateral hippocampus and right superior temporal gyrus, and decreased brain activity in the left superior frontal gyrus, left middle temporal gyrus, bilateral thalamus, left inferior frontal gyrus and right cerebellum. Mapping the abnormal patterns to the network atlas revealed the default mode network and the limbic system as core neural systems commonly affected in SLE. LIMITATIONS: The number of included studies is relatively small, with heterogeneous analytic methods and a risk of publication bias. CONCLUSIONS: Brain functional alterations in SLE are predominantly found in the default mode network and the limbic system. These findings uncovered a consistent pattern of resting-state functional network abnormalities in SLE which may serve as a potential objective neuroimaging biomarker.


Assuntos
Encefalopatias , Lúpus Eritematoso Sistêmico , Humanos , Imageamento por Ressonância Magnética/métodos , Rede de Modo Padrão , Sistema Límbico/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Mapeamento Encefálico
10.
Chem Commun (Camb) ; 60(27): 3677-3680, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38456735

RESUMO

A strategy for the preparation of hydrogel layer MXene membranes by an F-free method was proposed. It maintained high permeance (2686.1 L m-2 h-1 bar-1) and separation efficiency (99.99%) even after 300 min of emulsion separation. The membrane resisted harsh chemical and microbiological environments and efficiently treated actual oily wastewater.

11.
J Natl Compr Canc Netw ; 22(3)2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498975

RESUMO

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Instabilidade de Microssatélites , Estudos Retrospectivos , Estudos Prospectivos , Neoplasias Retais/genética , Neoplasias Retais/terapia , Terapia Neoadjuvante , Imunoterapia , Reparo de Erro de Pareamento de DNA , Neoplasias Colorretais/genética
12.
Sci Rep ; 14(1): 7393, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548831

RESUMO

Investigating the impact of train-induced vibration loads on soil hydraulic properties, this study conducted experiments using a self-designed indoor soil seepage platform that incorporates vibration loads. The experiments were complemented with scanning electron microscopy to analyze the influence of train-induced vibration loads on soil hydraulic conductivity and its evolutionary characteristics under different vibration frequencies. The experimental results indicated that as the vibration frequency increases from no vibration (0 Hz) to 20 Hz, the time required for the soil volumetric moisture content to reach its peak and stabilize decreases rapidly. However, after the vibration frequency exceeds 20 Hz, the rate at which the time required for the volumetric moisture content to reach its peak and stabilize decreases slows down. Furthermore, the soil pore water pressure increases with the increase in vibration frequency. At a vibration frequency of 80 Hz, the peak value of pore water pressure increases by 105% compared to the non-vibration state, suggesting that higher vibration frequencies promote the development and acceleration of soil pore moisture migration. Additionally, as the vibration frequency increases, the soil hydraulic conductivity initially experiences a rapid increase, with a growth rate ranging from 40.1 to 47.4%. However, after the frequency exceeds 20 Hz, this growth rate significantly decreases, settling to only 18.6% to 7.8%. When the soil was subjected to a vibration load, the scanning electron microscopy test revealed alterations in its pore structure. Micropores and small pores transformed into macropores and mesopores. Additionally, the microstructural parameters indicated that vibration load decreased the complexity of soil pores, thereby speeding up the hydraulic conduction process. This, in turn, affected the hydraulic properties of the soil and established a relationship between pore structure complexity and soil hydraulic properties.

13.
Microbiol Spectr ; 12(3): e0360223, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38315121

RESUMO

Horizontal gene transfer (HGT) is the process through which genetic information is transferred between different genomes and that played a crucial role in bacterial evolution. HGT can enable bacteria to rapidly acquire antibiotic resistance and bacteria that have acquired resistance is spreading within the microbiome. Conventional methods of characterizing HGT patterns include short-read metagenomic sequencing (short-reads mNGS), long-read sequencing, and single-cell sequencing. These approaches present several limitations, such as short-read fragments, high amounts of input DNA, and sequencing costs, respectively. Here, we attempt to circumvent present limitations to detect HGT by developing a metagenomics co-barcode sequencing workflow (MECOS) and applying it to the human and mouse gut microbiomes. In addition to that, we have over 10-fold increased contig length compared to short-reads mNGS; we also obtained exceeding 30 million paired reads with co-barcode information. Applying the novel bioinformatic pipeline, we integrated this co-barcoding information and the context information from long reads, and observed over 50-fold HGT events after we corrected the potential wrong HGT events. Specifically, we detected approximately 3,000 HGT blocks in individual samples, encompassing ~6,000 genes and ~100 taxonomic groups, including loci conferring tetracycline resistance through ribosomal protection. MECOS provides a valuable tool for investigating HGT and advance our understanding on the evolution of natural microbial communities within hosts.IMPORTANCEIn this study, to better identify horizontal gene transfer (HGT) in individual samples, we introduce a new co-barcoding sequencing system called metagenomics co-barcoding sequencing (MECOS), which has three significant improvements: (i) long DNA fragment extraction, (ii) a special transposome insertion, (iii) hybridization of DNA to barcode beads, and (4) an integrated bioinformatic pipeline. Using our approach, we have over 10-fold increased contig length compared to short-reads mNGS, and observed over 50-fold HGT events after we corrected the potential wrong HGT events. Our results indicate the presence of approximately 3,000 HGT blocks, involving roughly 6,000 genes and 100 taxonomic groups in individual samples. Notably, these HGT events are predominantly enriched in genes that confer tetracycline resistance via ribosomal protection. MECOS is a useful tool for investigating HGT and the evolution of natural microbial communities within hosts, thereby advancing our understanding of microbial ecology and evolution.


Assuntos
Transferência Genética Horizontal , Metagenômica , Animais , Humanos , Camundongos , Metagenômica/métodos , Biologia Computacional/métodos , Metagenoma , Bactérias/genética , DNA
14.
BMC Cancer ; 24(1): 164, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302968

RESUMO

BACKGROUND: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. METHODS: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. RESULTS: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. CONCLUSIONS: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.


Assuntos
Neoplasias Encefálicas , Neoplasias do Colo , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Síndromes Neoplásicas Hereditárias , Humanos , Estudos Retrospectivos , Oxaliplatina/uso terapêutico , Estadiamento de Neoplasias , Antígeno Carcinoembrionário , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Prognóstico , Quimioterapia Adjuvante
15.
Adv Mater ; : e2313247, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359440

RESUMO

Low-dimensional metal halide perovskites are an emerging class of light-emitting materials for LED-based displays; however, their B-site cations are confined to ns2 , d5, and d10 metals. Here, the design of divalent rare earth ions at B-site is presented and a novel Eu(II)-based iodide hybrid is reported with efficient (PLQY ≈98%) narrow-band (FWHM ≈43 nm) green emission and high thermal stability (97%@150 °C). Owing to reduced lattice vibrations and shrunken average distance of Eu(II)-iodide bonds in the face-sharing 1D-structure, photoluminescence from Eu(II) 4f-5d transition appears along with elevated crystal-field splitting of 5d energy level. The Eu(II)-based iodide hybrid is further demonstrated for color-pure green phosphor-converted LEDs with a maximum brightness of ≈396 000 cd m-2 and photoelectric efficiency of 29.2%. High-resolution micrometer-scale light-emitting diode (micro-LED) displays (2540 PPI) via the solution-processed screen is also presented. This work thus showcases a compelling narrow-band green emitter for commercial micro-LED displays.

16.
Phys Chem Chem Phys ; 26(6): 5589-5596, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38284319

RESUMO

Two-dimensional magnetic materials are attracting widespread attention not only for their excellent applications in spintronic devices but also for their potential to regulate valley splitting, which is crucial for valleytronics. Herein, we design a monolayer Janus ferromagnetic semiconductor T-CrSH by using first-principles calculations. We reveal that monolayer T-CrSH has a magnetic moment of 3µB per unit cell, which is primarily contributed by the 3d orbitals of the Cr atom. Monte Carlo simulations suggest that the Curie temperature of T-CrSH is 193 K, and it can rise to 402 K when a 5% tensile strain is applied. Furthermore, the valley degeneracy of WS2 can be lifted when monolayer T-CrSH is used as a substrate. The obtained valley splitting in the conduction band is 13.7 meV and that in the valence band is 157.5 meV. In addition, the large valley polarization of 12.8 meV in the conduction band makes it easy to achieve an electron-doped valley Hall current and spin Hall current when performing in an in-plane electric field.

17.
Cancer Lett ; 585: 216663, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38246221

RESUMO

Colorectal melanoma (CRM) is a rare malignant tumor with severe complications, and there is currently a lack of systematic research. We conducted a study that combined proteomics and mutation data of CRM from a cohort of three centers over a 16-years period (2005-2021). The patients were divided into a training set consisting of two centers and a testing set comprising the other center. Unsupervised clustering was conducted on the training set to form two molecular subtypes for clinical characterization and functional analysis. The testing set was used to validate the survival differences between the two subtypes. The comprehensive analysis identified two subtypes of CRM: immune exhausted C1 cluster and DNA repair C2 cluster. The former subtype exhibited characteristics of metabolic disturbance, immune suppression, and poor prognosis, along with APC mutations. A machine learning algorithm named Support Vector Machine (SVM) was applied to predict the classification of CRM patients based on protein expression in the external testing cohort. Two subtypes of primary CRM with clinical and proteomic characteristics provides a reference for subsequent diagnosis and treatments.


Assuntos
Neoplasias Colorretais , Melanoma , Humanos , Melanoma/genética , Multiômica , Estudos Prospectivos , Proteômica , Prognóstico
18.
J Int Med Res ; 52(1): 3000605231208570, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38190846

RESUMO

The differential diagnosis of isolated ophthalmoplegia includes a range of pathologies. In this case, a 26-year-old man of Han nationality presented with ophthalmoplegia. Neuroimaging revealed an atypical focal lesion in the interpeduncular fossa. Initial systemic workup indicated intracranial Mycobacterium tuberculosis infection, but there was no evidence to support a diagnosis of other autoimmune diseases (e.g., myasthenia gravis or multiple sclerosis). Neuroimaging follow-up over the next 3 years revealed progression from atypical solitary lesions to multifocal lesions in the white matter of the brain. Key immunological markers were observed in cerebrospinal fluid during follow-up, suggesting the evolution of multiple sclerosis. Ophthalmoplegia with a focal lesion in the interpeduncular fossa was an unusual set of symptoms indicating multiple sclerosis onset. The findings in this case suggest that M. tuberculosis infection is an important but overlooked factor involved in the pathogenesis of multiple sclerosis. Upon initial detection, atypical lesions should receive sufficient attention and patients should undergo systematic screening to identify M. tuberculosis infection and its associated immunological abnormalities.


Assuntos
Esclerose Múltipla , Miastenia Gravis , Mycobacterium tuberculosis , Oftalmoplegia , Tuberculose , Humanos , Adulto , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico , Seguimentos , Oftalmoplegia/diagnóstico , Oftalmoplegia/etiologia
19.
J Immunol ; 212(2): 208-215, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38166246

RESUMO

The gut microbiota, predominantly residing in the colon, is a complex ecosystem with a pivotal role in the host immune system. Dysbiosis of the gut microbiota has been associated with various diseases, and there is an urgent need to develop new therapeutics that target the microbiome and restore immune functions. This Brief Review discusses emerging therapeutic strategies that focus on oral delivery systems for modulating the gut microbiome. These strategies include genetic engineering of probiotics, probiotic-biomaterial hybrids, dietary fibers, and oral delivery systems for microbial metabolites, antimicrobial peptides, RNA, and antibiotics. Engineered oral formulations have demonstrated promising outcomes in reshaping the gut microbiome and influencing immune responses in preclinical studies. By leveraging these approaches, the interplay between the gut microbiota and the immune system can be harnessed for the development of novel therapeutics against cancer, autoimmune disorders, and allergies.


Assuntos
Doenças Autoimunes , Microbioma Gastrointestinal , Microbiota , Probióticos , Humanos , Sistema Imunitário , Probióticos/uso terapêutico , Disbiose
20.
Cell Rep ; 43(1): 113654, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38175757

RESUMO

Deficiency of DNA repair pathways drives the development of colorectal cancer. However, the role of the base excision repair (BER) pathway in colorectal cancer initiation remains unclear. This study shows that Nei-like DNA glycosylase 1 (NEIL1) is highly expressed in colorectal cancer (CRC) tissues and associated with poorer clinical outcomes. Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors. Furthermore, NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1 and subsequently promotes the production of immunosuppressive cytokines in CRC cells. A NEIL1 peptide suppresses intestinal tumorigenesis in ApcMin/+ mice, and targeting NEIL1 demonstrates a synergistic suppressive effect on tumor growth when combined with a nuclear factor κB (NF-κB) inhibitor. These results suggest that combined targeting of NEIL1 and NF-κB may represent a promising strategy for CRC therapy.


Assuntos
Neoplasias Colorretais , DNA Glicosilases , Animais , Camundongos , Carcinogênese , Linfócitos T CD8-Positivos/metabolismo , Neoplasias Colorretais/genética , DNA Glicosilases/metabolismo , Reparo do DNA , NF-kappa B/metabolismo
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