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1.
Imeta ; 3(2): e174, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38882499

RESUMO

The Lachnospiraceae family holds promise as a source of next-generation probiotics, yet a comprehensive delineation of its diversity is lacking, hampering the identification of suitable strains for future applications. To address this knowledge gap, we conducted an in-depth genomic and functional analysis of 1868 high-quality genomes, combining data from public databases with our new isolates. This data set represented 387 colonization-selective species-level clusters, of which eight genera represented multilineage clusters. Pan-genome analysis, single-nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography together shape the functional diversity of Lachnospiraceae. Moreover, analyses of associations with atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD) indicated that several strains of potentially novel Lachnospiraceae species possess the capacity to reduce the abundance of opportunistic pathogens, thereby imparting potential health benefits. Our findings shed light on the untapped potential of novel species enabling knowledge-based selection of strains for the development of next-generation probiotics holding promise for improving human health and disease management.

2.
Front Neurol ; 15: 1418247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882687

RESUMO

Background: Stroke survivors often face challenges in motor learning and motivation during rehabilitation, which can impede their recovery progress. Traditional rehabilitation methods vary in effectiveness, prompting the exploration of novel approaches such as reward strategies. Previous research indicates that rewards can enhance rehabilitation motivation and facilitate motor learning. However, most reward paradigms have utilized fixed reward amounts, which also have limitations. Exploring alternative, more effective reward strategies, such as probabilistic rewards, is warranted to optimize stroke patient rehabilitation. Methods: A total of 81 stroke patients will be recruited and randomly assigned to control, fixed reward, or probabilistic reward groups at a ratio of 1:1:1 using a randomized number table method. Participants will undergo 10 days of daily hand motor function rehabilitation training, with sessions lasting 20 min each. The training will involve pegboard tests and box and block tests. Control group participants will receive standard training, while fixed reward group members will receive monetary incentives for completing tests, and probabilistic reward group members will have the chance to win monetary rewards through a lottery box. Rehabilitation motivation and motor performance and functional near-infrared spectroscopy brain imaging will be conducted at designated time points. The primary outcome measure is the stroke rehabilitation motivation scale, and the second outcome measures include motor performance, simple test for evaluating hand function, motivation and pleasure scale self-report, and Pittsburgh rehabilitation participation scale. Discussion: Reward-based training enhance rehabilitation participation and adherence, it also improve motor learning speed and memory retention of stroke patients. The fixed reward applied in the past studies could diminish the sensitivity of stroke patients to rewards, while probabilistic reward may provide unpredictable or variable incentives or reinforcements for motor rehabilitation. This study will compare the efficacy of different reward strategies in enhancing motor learning ability and rehabilitation motivation among stroke patients. By conducting a randomized controlled trial, the study seeks to provide valuable insights into optimizing stroke rehabilitation protocols and improving patient outcomes.Clinical Trial Registration:https://www.chictr.org.cn/, ChiCTR2400082419.

3.
Sci Transl Med ; 16(752): eabq7074, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896602

RESUMO

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.


Assuntos
Receptores ErbB , Exantema , Inibidores de Janus Quinases , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Ratos , Administração Tópica , Afatinib/farmacologia , Afatinib/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Exantema/induzido quimicamente , Exantema/patologia , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases/metabolismo , Janus Quinases/antagonistas & inibidores , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Prospectivos
4.
Front Microbiol ; 15: 1379500, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873165

RESUMO

Introduction: Faecalibacterium is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of Faecalibacterium genomes from cultured strains and the distribution of different species in populations may differ among different sources. Methods: We here performed an extensive analysis of pan-genomes, functions, and safety evaluation of 136 Faecalibacterium genomes collected from 10 countries. Results: The genomes are clustered into 11 clusters, with only five of them were characterized and validly nomenclated. Over 80% of the accessory genes and unique genes of Faecalibacterium are found with unknown function, which reflects the importance of expanding the collection of Faecalibacterium strains. All the genomes have the potential to produce acetic acid and butyric acid. Nine clusters of Faecalibacterium are found significantly enriched in the healthy individuals compared with patients with type II diabetes.. Discussion: This study provides a comprehensive view of genomic characteristic and functions and of culturable Faecalibacterium bacterium from human gut, and enables clinical advances in the future.

5.
Front Neurol ; 15: 1390811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863513

RESUMO

Objective: Insufficient motivation among post-stroke survivors may be an important factor affecting their motor function recovery. This study seeks to investigate the relationship between motivation and functional recovery in stroke patients undergoing rehabilitation training. Materials and methods: 103 stroke patients with upper limb impairments were studied during their hospital stays. Assessments were done before and after rehabilitation training to measure motivation, emotional state, motor function, and independence in daily activities. Data analysis was conducted to examine the distribution of these factors among the participants. Pearson and Spearman correlation analyses were used to study the relationships between motivation, emotional state, and motor function. Patients were divided into high and low motivation groups based on the Rehabilitation Motivation Scale (RMS), and chi-square and rank-sum tests were used to compare functional differences before and after treatment among patients with varying levels of motivation. Results: 66 participants were found to have low motivation in the initial assessment of the RMS (64.08%). Consistency in motivation levels was observed among patients with high motivation (r = 0.648, P<0.001). Apathy was identified as the main factor affecting motivation in patients with low motivation (p = 0.027), while depression and anxiety were not significantly correlated. Motivation was strongly linked to improvements in upper limb motor function, daily living activities, and self-exercise duration (p < 0.001) for stroke patients undergoing rehabilitation. Post-training, there was a notable increase in motivation, motor function, and independence in daily activities (p < 0.001). Increased rehabilitation motivation was linked to better upper limb motor function and daily independence in patients, particularly those with low motivation. This correlation was significant for both the FMA-UE and FIM scores. Discussion: Old patients with poor upper limb motor function often have low motivation, which hinders their recovery. Using strategies to boost motivation in stroke patients with impaired upper limb function could greatly improve their rehabilitation and motor skills. It is crucial to prioritize these intervention strategies. Conclusion: Enhancing rehabilitation motivation in stroke patients with low motivation and upper limb motor impairments can foster the restoration of their functional capabilities.

6.
IEEE Trans Image Process ; 33: 3470-3485, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38809731

RESUMO

Recent years have witnessed the incredible performance boost of data-driven deep visual object trackers. Despite the success, these trackers require millions of sequential manual labels on videos for supervised training, implying the heavy burden of human annotating. This raises a crucial question: how to train a powerful tracker from abundant videos using limited manual annotations? In this paper, we challenge the conventional belief that frame-by-frame labeling is indispensable, and show that providing a small number of annotated bounding boxes in each video is sufficient for training a strong tracker. To facilitate that, we design a novel SParsely-supervised Object Tracking (SPOT) framework. It regards the sparsely annotated boxes as anchors and progressively explores in the temporal span to discover unlabeled target snapshots. Under the teacher-student paradigm, SPOT leverages the unique transitive consistency inherent in the tracking task as supervision, extracting knowledge from both anchor snapshots and unlabeled target snapshots. We also utilize several effective training strategies, i.e., IoU filtering, asymmetric augmentation, and temporal calibration to further improve the training robustness of SPOT. The experimental results demonstrate that, given less than 5 labels for each video, trackers trained via SPOT perform on par with their fully-supervised counterparts. Moreover, our SPOT exhibits two desirable properties: 1) SPOT enables us to fully exploit large-scale video datasets by efficiently allocating sparse labels to more videos even under a limited labeling budget; 2) when equipped with a target discovery module, SPOT can even learn from purely unlabeled videos for performance gain. We hope this work could inspire the community to rethink the current annotation principles and make a step towards practical label-efficient deep tracking.

7.
Br J Pharmacol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698493

RESUMO

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes. EXPERIMENTAL APPROACH: Adult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation. KEY RESULTS: Post-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation. CONCLUSIONS AND IMPLICATIONS: Post-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

8.
RSC Adv ; 14(20): 13944-13945, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38686303

RESUMO

[This corrects the article DOI: 10.1039/D0RA05640E.].

9.
Bioorg Chem ; 147: 107369, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640721

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a complex pathogenic metabolic syndrome characterized by increased inflammation and endoplasmic reticulum stress. In recent years, natural polysaccharides derived from traditional Chinese medicine have shown significant anti-inflammatory effects, making them an attractive therapeutic option. However, little research has been conducted on the therapeutic potential of dried tangerine peel polysaccharide (DTPP) - one of the most important medicinal resources in China. The results of the present study showed that DTPP substantially reduced macrophage infiltration in vivo and suppressed the expression of pro-inflammatory factors and endoplasmic reticulum stress-related genes. Additionally, surface plasmon resonance analysis revealed that DTPP had a specific affinity to myeloid differentiation factor 2, which consequently suppressed lipopolysaccharide-induced inflammation via interaction with the toll-like receptor 4 signaling pathway. This study provides a potential molecular mechanism underlying the anti-inflammatory effects of DTPP on NAFLD and suggests DTPP as a promising therapeutic strategy for NAFLD treatment.


Assuntos
Estresse do Retículo Endoplasmático , Inflamação , Polissacarídeos , Receptor 4 Toll-Like , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Polissacarídeos/farmacologia , Polissacarídeos/química , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Antígeno 96 de Linfócito/antagonistas & inibidores , Antígeno 96 de Linfócito/metabolismo , Carthamus tinctorius/química , Camundongos Endogâmicos C57BL , Estrutura Molecular , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
10.
Biomaterials ; 307: 122512, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38430646

RESUMO

Proteotoxic stress, caused by the accumulation of abnormal unfolded or misfolded cellular proteins, can efficiently activate inflammatory innate immune response. Initiating the mitochondrial proteotoxic stress might go forward to enable the cytosolic release of intramitochondrial DNA (mtDNA) for the immune-related mtDNA-cGAS-STING activation, which however is easily eliminated by a cell self-protection, i.e., mitophagy. In light of this, a nanoinducer (PCM) is reported to trigger mitophagy-inhibited cuproptotic proteotoxicity. Through a simple metal-phenolic coordination, PCMs reduce the original Cu2+ with the phenolic group of PEG-polyphenol-chlorin e6 (Ce6) into Cu+. Cu+ thereby performs its high binding affinity to dihydrolipoamide S-acetyltransferase (DLAT) and aggregates DLAT for cuproptotic proteotoxic stress and mitochondrial respiratory inhibition. Meanwhile, intracellular oxygen saved from the respiratory failure can be utilized by PCM-conjugated Ce6 to boost the proteotoxic stress. Next, PCM-loaded mitophagy inhibitor (Mdivi-1) protects proteotoxic products from being mitophagy-eliminated, which allows more mtDNA to be released in the cytosol and successfully stimulate the cGAS-STING signaling. In vitro and in vivo studies reveal that PCMs can upregulate the tumor-infiltrated NK cells by 24% and enhance the cytotoxic killing of effector T cells. This study proposes an anti-tumor immunotherapy through mitochondrial proteotoxicity.


Assuntos
DNA Mitocondrial , Neoplasias , Estresse Proteotóxico , Mitocôndrias , Nucleotidiltransferases , Imunoterapia , Di-Hidrolipoil-Lisina-Resíduo Acetiltransferase , Neoplasias/terapia
11.
Heliyon ; 10(5): e27270, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463766

RESUMO

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

12.
Adv Mater ; 36(19): e2312588, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38316447

RESUMO

Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.


Assuntos
Epigênese Genética , Imunoterapia , Proteínas Proto-Oncogênicas c-myc , Radiossensibilizantes , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Epigênese Genética/efeitos dos fármacos , Terapia de Imunossupressão/métodos , Imunoterapia/métodos , Interferon Tipo I/metabolismo , Nanopartículas/química , Neoplasias/terapia , Neoplasias/imunologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Radiossensibilizantes/farmacologia , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Metilases de Modificação do DNA/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico
13.
Int J Biol Macromol ; 262(Pt 1): 129998, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336326

RESUMO

How to effectively improve the poor interfacial adhesion between polylactic acid/poly(butylene adipate-co-terephthalate) (PLA/PBAT) matrix and thermoplastic starch (TPS) is still a challenge. Therefore, this work aims to introduce a convenient method to enhance the performance of PLA/PBAT/TPS blend by melt reactive extrusion. Here, using 4,4'-methylene-bis(N,N-diglycidyl-aniline) (MBDG) containing four epoxy groups as a reactive compatibilizer, and respectively using 1-methylimidazole (MI) or triethylenediamine (TD) as a catalyzer, serial PLA/PBAT/TPS ternary bio-composites are successfully prepared via melt reactive extrusion. The results showed that, under the catalysis of organic base, especially MI, the epoxy groups of MBDG can effectively react with hydroxyl and carboxyl groups of PLA/PBAT and hydroxyl groups in TPS to form chain-expanded and cross-linked structures. The tensile strength of the composites is increased by 20.0 % from 21.1 MPa, and the elongation at break is increased by 182.4 % from 17.6 % owing to the chain extension and the forming of cross-linked structures. The molecular weight, thermal stability, crystallinity, and surface hydrophobicity of the materials are gradually improved with the increase of MBDG content. The melt fluidity of the composites is also improved due to the enhancement of compatibility. The obtained PLA/PBAT/TPS materials have the potential to be green plastic products with good properties.


Assuntos
Alcenos , Resinas Epóxi , Ácidos Ftálicos , Poliésteres , Adipatos , Amido
14.
Tissue Cell ; 87: 102324, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354685

RESUMO

Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle.


Assuntos
Ácido Láctico , Proteínas Quinases p38 Ativadas por Mitógeno , Espécies Reativas de Oxigênio/metabolismo , Ácido Láctico/metabolismo , Ácido Láctico/farmacologia , Diferenciação Celular , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Mioblastos/metabolismo
15.
Heliyon ; 10(4): e26270, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38375243

RESUMO

The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the "molecular-cellular" mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.

16.
Sci Rep ; 14(1): 1292, 2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-38221534

RESUMO

The Illumina HiSeq platform has been a commonly used option for bacterial genome sequencing. Now the BGI DNA nanoball (DNB) nanoarrays platform may provide an alternative platform for sequencing of bacterial genomes. To explore the impact of sequencing platforms on bacterial genome assembly, quality assessment, sequence alignment, functional annotation, mutation detection, and metagenome mapping, we compared genome assemblies based on sequencing of cultured bacterial species using the HiSeq 2000 and BGISEQ-500 platforms. In addition, simulated reads were used to evaluate the impact of insert size on genome assembly. Genome assemblies based on BGISEQ-500 sequencing exhibited higher completeness and fewer N bases in high GC genomes, whereas HiSeq 2000 assemblies exhibited higher N50. The majority of assembly assessment parameters, sequences of 16S rRNA genes and genomes, numbers of single nucleotide variants (SNV), and mapping to metagenome data did not differ significantly between platforms. More insertions were detected in HiSeq 2000 genome assemblies, whereas more deletions were detected in BGISEQ-500 genome assemblies. Insert size had no significant impact on genome assembly. Taken together, our results suggest that DNBSEQ platforms would be a valid substitute for HiSeq 2000 for bacterial genome sequencing.


Assuntos
DNA , Genoma Bacteriano , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Bactérias/genética
18.
Adv Healthc Mater ; 13(6): e2302811, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37909376

RESUMO

Malignant melanoma is an aggressive skin cancer with a high metastatic and mortality rate. Owing to genetic alterations, melanoma cells are resistant to apoptosis induction, which reduces the efficacy of most adjuvant systemic anticancer treatments in clinical. Here, a noninvasive strategy for anti-melanoma immunotherapy based on a manganese-coordinated nanomedicine is provided. Supplemented with photoirradiation, photon-mediated reactive oxygen species generation by photosensitizer chlorin e6 initiates photon-controlled pyroptosis activation (PhotoPyro) and promotes antitumor immunity. Simultaneously, photoirradiation-triggered double-stranded DNA generation in the cytosol would activate the Mn2+ -sensitized cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which further augment the PhotoPyro-induced immune response. The syngeneic effect of these immunostimulatory pathways significantly benefits dendritic cell maturation by damage-associated molecular patterns and proinflammatory cytokines secretion, thereby activating T cells and remarkably eliciting a systemic antitumor immune response to inhibiting both primary and distant tumor growth. Collaboratively, the photoirradiation-triggered PhotoPyro and cGAS-STING pathway activation by nanomedicine administration could enhance the antitumor capacity of immunotherapy and serve as a promising strategy for melanoma treatment.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/terapia , Manganês/farmacologia , Nanomedicina , Imunoterapia
19.
Lett Appl Microbiol ; 77(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38126115

RESUMO

An important risk factor for cardiovascular disease is dyslipidemia, especially abnormal cholesterol levels. The relation between probiotics and cholesterol-lowering capability has been extensively studied. Lactobacillus acidophilus plays a significant role in affecting host health, and produces multitudinous metabolites, which have prohibitory functions against pathogenic microorganisms. In this study, we identified a cholesterol-lowering strain AM13-1, isolated from a fecal sample obtained from a healthy adult male, and performed comprehensive function analysis by whole-genome analysis and in vitro experiments. Genome analyses of L. acidophilus AM13-1 revealed that carbohydrate and amino acid transport, metabolism, translation, ribosomal structure, and biogenesis are abundant categories of functional genes. No virulence factors or toxin genes with experimentally verified were found in the genome of strain AM13-1. Besides, plenty of probiotic-related genes were predicted from the L. acidophilus AM13-1 genome, such as cbh, atpA-D, and dltD, with functions related to cholesterol-lowering and acid resistance. And strain AM13-1 showed high-efficiency of bile salt hydrolase activity and the capacity for removing cholesterol with efficiency rates of 70%. These function properties indicate that strain AM13-1 can be considered as a probiotic candidate for use in food and health care products.


Assuntos
Lactobacillus acidophilus , Probióticos , Humanos , Masculino , Lactobacillus acidophilus/genética , Lactobacillus acidophilus/metabolismo , Probióticos/metabolismo , Colesterol/metabolismo , Fezes
20.
J Appl Microbiol ; 134(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38040628

RESUMO

AIMS: Lactobacillus acidophilus has been extensively applied in plentiful probiotic products. Although several studies have been performed to investigate the beneficial characteristics and genome function of L. acidophilus, comparative genomic analysis remains scarce. In this study, we collected 74 L. acidophilus genomes from our gut bacterial genome collection and the public database and conducted a comprehensive comparative genomic analysis. METHODS AND RESULTS: This study revealed the potential correlation of the genomic diversity and niche adaptation of L. acidophilus from different perspectives. The pan-genome of L. acidophilus was found to be open, with metabolism, information storage, and processing genes mainly distributed in the core genome. Phage- and peptidase-associated genes were found in the genome of the specificity of animal-derived strains, which were related to the adaptation of the animal gut. SNP analysis showed the differences of the utilization of vitamin B12 in cellular of L. acidophilus strains from animal gut and others. CONCLUSIONS: This work provides new insights for the genomic diversity analysis of L. acidophilus and uncovers the ecological adaptation of the specific strains.


Assuntos
Lactobacillus acidophilus , Probióticos , Animais , Lactobacillus acidophilus/genética , Genoma Bacteriano , Genômica
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