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1.
BMC Vet Res ; 20(1): 242, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831422

ABSTRACT

BACKGROUND: ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. RESULTS: This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities. CONCLUSIONS: The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.


Subject(s)
Adenosine Triphosphatases , Antioxidants , Gastrointestinal Microbiome , Jejunum , Animals , Jejunum/microbiology , Jejunum/enzymology , Antioxidants/metabolism , Gastrointestinal Microbiome/physiology , Adenosine Triphosphatases/metabolism , Sheep , Male , Malondialdehyde/metabolism , Superoxide Dismutase/metabolism
2.
Cancer Immunol Immunother ; 73(8): 151, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832951

ABSTRACT

BACKGROUND: Immunotherapy for gastric cancer remains a challenge due to its limited efficacy. Metabolic reprogramming toward glycolysis has emerged as a promising avenue for enhancing the sensitivity of tumors to immunotherapy. Pyruvate dehydrogenase kinases (PDKs) play pivotal roles in regulating glycolysis. The importance of PDKs in the context of gastric cancer immunotherapy and their potential as therapeutic targets have not been fully explored. METHODS: PDK and PD-L1 expression was analyzed using data from the GSE66229 and The Cancer Genome Atlas (TCGA) cohorts. Additionally, the Immune Checkpoint Blockade Therapy Atlas (ICBatlas) database was utilized to assess PDK expression in an immune checkpoint blockade (ICB) therapy group. Subsequently, the upregulation of PD-L1 and the enhancement of anticancer effects achieved by targeting PDK were validated through in vivo and in vitro assays. The impact of PDK on histone acetylation was investigated using ChIP‒qPCR to detect changes in histone acetylation levels. RESULTS: Our analysis revealed a notable negative correlation between PD-L1 and PDK expression. Downregulation of PDK led to a significant increase in PD-L1 expression. PDK inhibition increased histone acetylation levels by promoting acetyl-CoA generation. The augmentation of acetyl-CoA production and concurrent inhibition of histone deacetylation were found to upregulate PD-L1 expression in gastric cancer cells. Additionally, we observed a significant increase in the anticancer effect of PD-L1 antibodies following treatment with a PDK inhibitor. CONCLUSIONS: Downregulation of PDK in gastric cancer cells leads to an increase in PD-L1 expression levels, thus potentially improving the efficacy of PD-L1 immune checkpoint blockade therapy.


Subject(s)
B7-H1 Antigen , Glycolysis , Immunotherapy , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Stomach Neoplasms , Up-Regulation , B7-H1 Antigen/metabolism , Humans , Animals , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/immunology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Immunotherapy/methods , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays , Mice, Nude
3.
PeerJ ; 12: e17480, 2024.
Article in English | MEDLINE | ID: mdl-38827288

ABSTRACT

Background: Barbronia, a genus of freshwater macrophagous leeches, belongs to Erpobdelliformes (Salifidae: Clitellata: Annelida), and B. weberi, a well-known leech within this genus, has a worldwide distribution. However, the systematics of Barbronia have not yet been adequately investigated, primarily due to a few molecular markers, and only 20 Barbronia sequences available in the GenBank database. This gap significantly limits our understanding of the Barbronia species identification, as well as the phylogenetic placement of the genus Barbronia within Salifidae. Methods: Next-generation sequencing (NGS) was used to simultaneously capture the entire mitochondrial genome and the full-length 18S/28S rDNA sequences. The species boundary of Barbronia species was estimated using bGMYC and bPTP methods, based on all available Barbronia COI sequences. Uncorrected COI p-distance was calculated in MEGA. A molecular data matrix consisting of four loci (COI, 12S, 18S, and 28S rDNA) for outgroups (three Haemopis leeches) and 49 erpobdellid leeches, representing eight genera within the Suborder Erpobdelliformes was aligned using MAFFT and LocARNA. This matrix was used to reconstruct the phylogenetic relationship of Barbronia via Bayesian inference (BI) and the maximum likelihood (ML) method. Results: The full lengths of the mitochondrial genome, 18S and 28S rDNAs of B. cf. gwalagwalensis, are 14847 bp, 1876 bp 1876 bp, and 2863 bp, respectively. Both bGMYC and bPTP results based on COI data are generally congruent, suggesting that the previously proposed taxa (B. arcana, B. weberi formosana, and B. wuttkei or Erpobdella wuttkei) are synonyms of B. weberi. The specimens listed in the B. gwalagwalensis group, however, are split into at least two Primary Species Hypotheses (PSHs). The p-distance of the first PSH is less than 1.3% but increased to 4.5% when including the secondary PSH (i.e., B. cf. gwalagwalensis). In comparison, the interspecific p-distance between the B. weberi group and the B. gwalagwalensis group ranged from 6.4% to 8.7%, and the intraspecific p-distance within the B. weberi group is less than 0.8%. Considering the species delimitation results and the sufficient large p-distance, the specimen sampled in China is treated as B. cf. gwalagwalensis. The monophyly of the four Erpobdelliformes families Salifidae, Orobdellidae, Gastrostomobdellidae sensu stricto and Erpobdellidae is well supported in ML and BI analysis based on a data of four markers. Within the Salifidae, a well-supported Barbronia is closely related to a clade containing Odontobdella and Mimobdella, and these three genera are sister to a clade consisted of Salifa and Linta. According to the results of this study, the strategy of simultaneous obtaining both whole mitochondria and nuclear markers from extensively sampled Salifids species using NGS is expected to fathom both the species diversity of B. gwalagwalensis and the evolutionary relationship of Salifidae.


Subject(s)
Phylogeny , Animals , Genome, Mitochondrial/genetics , Leeches/genetics , Leeches/classification , High-Throughput Nucleotide Sequencing , RNA, Ribosomal, 28S/genetics
4.
J Vasc Surg ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38777158

ABSTRACT

OBJECTIVE: Spontaneous carotid artery dissections (sCAD) are the common cause of stroke in middle-aged and young people. There is still a lack of clinical classification to guide the management of sCAD. We reviewed our experience with 179 sCAD patients and proposed a new classification for sCAD with prognostic and therapeutic significance. METHODS: This is a retrospective review of prospectively collected data from June 2018 to June 2023 of sCAD patients treated at a large tertiary academic institution in an urban city in China. Based on imaging results, we categorize sCAD into four types. Type Ⅰ: intramural hematoma or dissection with < 70% luminal narrowing; type Ⅱ: intramural hematoma or dissection with ≥ 70% luminal narrowing; type Ⅲ: dissecting aneurysm; type ⅣA: extracranial carotid artery occlusion; type ⅣB: tandem occlusion. We compared the clinical data and prognostic outcomes among various types of sCAD. RESULTS: A total of 179 patients and 197 dissected arteries met the inclusion criteria. The mean age of the 179 sCAD patients was 49.5 years, 78% were male, 18 patients (10%) had bilateral sCAD. According to our classification, there were 56 (28.4%) type Ⅰ, 50 (25.4%) type Ⅱ, 60 (30.5%) type Ⅲ, and 31 (15.7%) type Ⅳ dissections. During a mean hospitalization length of 11.4±47.0 days, there were 9 recurrent strokes (4.6%) after medical treatment, 2 (1.0%) type Ⅲ dissections, 7 (3.6%) type Ⅳ dissections, all ipsilateral, and 1 death. Overall, there were 7 (3.6%, 1 type Ⅰ dissection, 3 type Ⅱ dissections, 2 type Ⅲ dissections, and 1 type Ⅳ dissection) recurrent stroke and 3 (1.5%, all type Ⅲ dissections) recurrent TIA in patients treated with just medical therapy during the follow-up period, all ipsilateral, with a mean follow-up of 26 months (3-59 months). These patients did not undergo further intervention due to the high difficulty associated with endovascular treatment or the mild nature of recurrent cerebral ischemic symptoms. Twenty-nine (51.8%) type I dissections were completely recanalized after antithrombotic therapy. A total of 19 (38 %) of type II dissections and 44 (73%) of type III dissections received endovascular treatment (EVT) for persistent flow-limited dissections, enlargement of dissecting aneurysms, or aggravation of neurological symptoms despite antithrombotic therapy. Type Ⅳ dissections are more likely to lead to the occurrence of ischemic stroke and presented with more severe symptoms. Eight (33%) type IVB dissections received acute phase intervention due to distal thromboembolism or aggravation of neurological symptoms after medical treatment. In terms of cerebral ischemic events and mortality, there were no statistically significant differences among the four types of sCAD (all p > .05). Favorable outcome was achieved in 168 (93.9%) patients. CONCLUSIONS: This study proposed a novel and more comprehensive classification method and the modern management strategy for sCAD. Antithrombotic therapy is beneficial to reduce the risk of recurrent stroke for stable sCAD. Non-emergent EVT can be an alternative therapeutic approach for patients who meet indications as in type II to IVA dissections. Urgent procedure with neurovascular intervention is necessary for some type IVB dissections. The short-term results of EVT for sCAD are encouraging, and long-term device-related and functional outcome should undergo further research.

5.
J Am Chem Soc ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814730

ABSTRACT

Combining metal-organic frameworks (MOFs) with liquid crystals to construct liquid crystalline MOFs (LCMOF) offers the advantage of endowing and enhancing their functionality, yet it remains a challenging task. Herein, we report chiral liquid crystalline MOF (CLCMOF) thin films by cross-linking the chiral liquid crystals (CLC) with MOF thin films to realize highly circular polarization luminescence (CPL) performance with photo and thermal switching. By layer by layer cross-linking stilbene-containing CLC with stilbene-based MOF (CLC/MOF) thin film, the CLCMOF thin films were successfully obtained after UV irradiation due to the abundant [2 + 2] photocycloaddition. The resulted CLCMOF thin films have strong chirality, obvious photochromic fluorescent, and strong CPL performance (the asymmetry factor reaches to 0.4). Furthermore, due to the photochromic fluorescent MOF and thermotropic CLC, the CPL can be reversed and red-shifted after heating and UV irradiation treatment, showing photo- and thermal CPL switching. Such MOF-based CPL thin films with photo/thermal CPL switching were prepared to patterns and codes for the demonstration of potential application in advanced information anticounterfeit and encryption. This study not only opens a strategy for developing chiral thin films combining MOFs and liquid crystals but also offers a new route to achieve CPL switching in optical applications.

6.
Adv Drug Deliv Rev ; 210: 115343, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782093
7.
Cell Metab ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38703762

ABSTRACT

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

8.
Asian J Surg ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38744652
9.
Nat Commun ; 15(1): 4009, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740761

ABSTRACT

Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

10.
J Health Popul Nutr ; 43(1): 63, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741213

ABSTRACT

BACKGROUND: According to national guidelines, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is a second-line therapy option for irritable bowel syndrome (IBS) and improves functional intestinal symptoms. Numerous noteworthy results have been published in this field over the past fifteen years. This study aims to analyze the global research trend and hotspot of the low FODMAP diet research, and provide a comprehensive perspective and direction for researchers. METHODS: The Science Citation Index-Expanded of the Web of Science Core Collection (WoSCC) was used to identify low FODMAP diet-related articles and reviews. Three bibliometric programs (CiteSpace, VOSviewer, Scimago Graphic) were utilized to analyze and visualize the annual publications, authors, countries, institutions, journals, citations, and keywords. RESULTS: In total, 843 documents related to the low FODMAP diet research were published in 227 journals by 3,343 authors in 1,233 institutions from 59 countries. The United States, which was the most engaged nation in international collaboration, had the largest annual production and the fastest growth. The most productive organization was Monash University, and the most fruitful researcher was Gibson PR. Nutrients ranked first in terms of the number of published documents. The article "A diet low in FODMAPs reduces symptoms of irritable bowel syndrome" (Halmos EP, 2014) received the most co-citations. Keywords that appear frequently in the literature mainly involve two main aspects: the clinical efficacy evaluation and mechanism exploration of the low FODMAP diet. The term "gut microbiota" stands out as the most prominent keyword among the burst keywords that have remained prevalent till date. CONCLUSION: The restriction stage of the low FODMAP diet is superior to other dietary therapies for IBS in terms of symptom response, but it has a negative impact on the abundance of gut Bifidobacteria and diet quality. Identification of biomarkers to predict response to the low FODMAP diet is of great interest and has become the current research hotspot.


Subject(s)
Bibliometrics , Diet, Carbohydrate-Restricted , Fermentation , Irritable Bowel Syndrome , Oligosaccharides , Humans , Irritable Bowel Syndrome/diet therapy , Diet, Carbohydrate-Restricted/methods , Oligosaccharides/administration & dosage , Disaccharides/administration & dosage , Monosaccharides/analysis , Polymers , Biomedical Research , FODMAP Diet
11.
Sci Rep ; 14(1): 11299, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760436

ABSTRACT

The relationship between the Systemic Inflammatory Response Index (SIRI) and the Fibrinogen-to-albumin ratio (FAR) has not been extensively investigated. The objective of this study was to determine the independent relationship between FAR and SIRI in people with osteoporotic fractures (OPF). A cross-sectional study was conducted using retrospective data from 3431 hospitalized OPF patients. The exposure variable in this study was the baseline FAR, while the outcome variable was the SIRI. Covariates, including age, gender, BMI, and other clinical and laboratory factors, were adjusted. Cross-correlation analysis and linear regression models were applied. The generalized additive model (GAM) investigated non-linear relationships. Adjusted analysis revealed an independent negative association between FAR and SIRI in OPF patients (ß = - 0.114, p = 0.00064, 95% CI - 0.180, - 0.049). A substantial U-shaped association between FAR and SIRI was shown using GAM analysis (p < 0.001). FAR and SIRI indicated a negative association for FAR below 6.344% and a positive correlation for FAR over 6.344%. The results of our study revealed a U-shaped relationship between SIRI and FAR. The lowest conceivable FAR for a bone-loose inflammatory disease might be 6.344%, suggesting that this has particular significance for the medical diagnosis and therapy of persons with OPF. Consequently, the term "inflammatory trough" is proposed. These results offer fresh perspectives on controlling inflammation in individuals with OPF and preventing inflammatory osteoporosis.


Subject(s)
Fibrinogen , Osteoporotic Fractures , Humans , Female , Fibrinogen/metabolism , Fibrinogen/analysis , Male , Osteoporotic Fractures/blood , Osteoporotic Fractures/epidemiology , Aged , Cross-Sectional Studies , Retrospective Studies , Middle Aged , Inflammation/blood , Aged, 80 and over , Serum Albumin/analysis
12.
Heliyon ; 10(9): e30641, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765098

ABSTRACT

Background: Lung adenosquamous carcinoma (ASC) is a rare tumor with high invasive and metastatic potential. Few studies have explored metastatic patterns in patients with advanced-stage ASC. Methods: Patients diagnosed with ASC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015 were selected. Descriptive statistics were obtained to characterize the metastatic sites of the study participants. The Kaplan-Meier method was applied to compare survival curves among patients with different metastatic patterns. Cox regression analysis was performed to evaluate risk factors for metastasis. Results: A total of 858 eligible patients with ASC were enrolled; the mean age was 71.5 years (standard deviation ± 7.8 years). There was a slightly higher proportion of male patients (54.0 %). A total of 63.2 % of patients harbored single-site metastasis (median OS: 5 months), 23.6 % of patients had two-site metastasis (median OS: 4 months), and approximately 10 % of patients harbored three or more sites metastasis (median OS: 3 months). Bone (56.9 %) was the most frequent site of metastasis (median OS: 4 months), followed by lung metastasis (37.6 %, median OS: 5 months), liver metastasis (22.1 %, median OS: 5 months), and brain metastasis (21.4 %, median OS: 4 months). Chemotherapy decreased the risk of death by 70 % (HR = 0.296, 95 % CI 0.241-0.363), 70 % (HR = 0.302, 95 % CI 0.224-0.406), 78 % (HR = 0.218, 95 % CI 0.151-0.314), and 70 % (HR = 0.302, 95 % CI 0.231-0.396) in patients harboring bone, liver, brain and lung metastases, respectively. The brain increased the risk of death by 50 % (HR = 1.501, 95 % CI 1.209-1.865), 64 % (HR = 1.644, 95 % CI 1.126-2.402), and 128 % (HR = 2.284, 95 % CI 1.653-3.157) in patients harboring bone, liver and lung metastases, respectively. Conclusion: Patients with advanced-stage ASC have unfavorable outcomes. Early detection and aggressive treatment can improve patients outcomes.

13.
Osteoporos Int ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771526

ABSTRACT

This large-scale prospective study showed that a significant association between longer duration of daily outdoor walking and reduced osteoporosis risk was found among older adults, particularly among those with a low genetic predisposition to osteoporosis, which highlighted the importance of outdoor walking as a simple, cost-effective adjunct for preventing osteoporosis. PURPOSE: The available cross-sectional data and small-scale studies indicate that outdoor walking benefits bone metabolism. Nevertheless, there is a scarcity of comprehensive prospective research investigating the enduring correlation between outdoor walking and osteoporosis. This study aims to conduct a prospective analysis of the correlation between outdoor walking and osteoporosis while also examining potential variations influenced by genetic susceptibility to osteoporosis. METHODS: 24,700 older adults without osteoporosis at baseline were enrolled. These individuals were followed up until December 31, 2021, during which data on outdoor walking was gathered. The genetic risk score for osteoporosis was comprised of 14 single-nucleotide polymorphisms. RESULTS: 4,586 cases of osteoporosis were identified throughout a median follow-up period of 37.3 months. Those who walked outside for > 30 but ≤ 60 min per day had a hazard ratio (HR) of 0.83 (95% confidence interval (CI): 0.72-0.95) for incident osteoporosis, whereas those who walked outside for > 60 min per day had an HR of 0.60 (95% CI: 0.39-0.92). We found that osteoporosis risk exhibited a declining trend in individuals with low genetic risk. Individuals walking outside for > 60 min per day tended to have the lowest overall osteoporosis risk among those with high genetic risk. CONCLUSIONS: A significant negative correlation exists between an extended period of daily outdoor walking and osteoporosis incidence risk. This correlation is particularly pronounced among individuals with low genetic risk. The results above underscore the significance of outdoor walking as a simple and economical adjunct to public health programs to prevent osteoporosis.

14.
Nat Commun ; 15(1): 3987, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734698

ABSTRACT

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.


Subject(s)
Blood-Brain Barrier , Brain , Cerebrovascular Circulation , Nanoparticles , Vinca Alkaloids , Animals , Vinca Alkaloids/pharmacology , Vinca Alkaloids/pharmacokinetics , Vinca Alkaloids/administration & dosage , Vinca Alkaloids/chemistry , Nanoparticles/chemistry , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Mice , Cerebrovascular Circulation/drug effects , Male , Brain/metabolism , Brain/drug effects , Brain/blood supply , Humans , Neuroprotective Agents/pharmacokinetics , Neuroprotective Agents/pharmacology , Mice, Inbred C57BL , Tissue Distribution , Drug Delivery Systems , Mice, Transgenic
15.
Front Immunol ; 15: 1407649, 2024.
Article in English | MEDLINE | ID: mdl-38812510

ABSTRACT

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists.


Subject(s)
Papillomaviridae , Papillomavirus Infections , Toll-Like Receptors , Humans , Toll-Like Receptors/metabolism , Toll-Like Receptors/agonists , Toll-Like Receptors/immunology , Papillomavirus Infections/immunology , Papillomavirus Infections/therapy , Papillomavirus Infections/virology , Papillomaviridae/physiology , Papillomaviridae/immunology , Signal Transduction , Neoplasms/therapy , Neoplasms/immunology , Animals , Immunotherapy/methods , Female , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/immunology , Host-Pathogen Interactions/immunology
16.
J Nanobiotechnology ; 22(1): 215, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693585

ABSTRACT

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs.


Subject(s)
Cell Culture Techniques, Three Dimensional , Extracellular Vesicles , Stem Cells , Extracellular Vesicles/metabolism , Humans , Stem Cells/cytology , Stem Cells/metabolism , Animals , Cell Culture Techniques, Three Dimensional/methods , Cell Culture Techniques/methods
17.
ACS Nano ; 18(21): 13583-13598, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38740518

ABSTRACT

A significant gap exists in the demand for safe and effective drugs for inflammatory bowel disease (IBD), and its associated intestinal fibrosis. As oxidative stress plays a central role in the pathogenesis of IBD, astaxanthin (AST), a good antioxidant with high safety, holds promise for treating IBD. However, the application of AST is restricted by its poor solubility and easy oxidation. Herein, different protein-based nanoparticles (NPs) are fabricated for AST loading to identify an oral nanovehicle with potential clinical applicability. Through systematic validation via molecular dynamics simulation and in vitro characterization of properties, whey protein isolate (WPI)-driven NPs using a simple preparation method without the need for cross-linking agents or emulsifiers were identified as the optimal carrier for oral AST delivery. Upon oral administration, the WPI-driven NPs, benefiting from the intrinsic pH sensitivity and mucoadhesive properties, effectively shielded AST from degradation by gastric juices and targeted release of AST at intestinal lesion sites. Additionally, the AST NPs displayed potent therapeutic efficacy in both dextran sulfate sodium (DSS)-induced acute colitis and chronic colitis-associated intestinal fibrosis by ameliorating inflammation, oxidative damage, and intestinal microecology. In conclusion, the AST WPI NPs hold a potential therapeutic value in treating inflammation and fibrosis in IBD.


Subject(s)
Inflammatory Bowel Diseases , Nanoparticles , Prebiotics , Reactive Oxygen Species , Whey Proteins , Whey Proteins/chemistry , Whey Proteins/pharmacology , Animals , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/pathology , Reactive Oxygen Species/metabolism , Administration, Oral , Nanoparticles/chemistry , Prebiotics/administration & dosage , Fibrosis/drug therapy , Inflammation/drug therapy , Inflammation/pathology , Inflammation/metabolism , Mice , Xanthophylls/pharmacology , Xanthophylls/chemistry , Xanthophylls/administration & dosage , Dextran Sulfate , Mice, Inbred C57BL , Male , Antioxidants/chemistry , Antioxidants/pharmacology , Humans
18.
J Med Case Rep ; 18(1): 140, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38566262

ABSTRACT

BACKGROUND: Castleman's disease is a rare lymphoproliferative disorder that is often misdiagnosed because of its untypical clinical or imaging features except for a painless mass. Besides, it is also difficult to cure Castleman's disease due to its unclear pathogenesis. CASE PRESENTATION: We present a Castleman's disease case with diagnostic significance regarding a 54-year-old Chinese male who has a painless mass in his left parotid gland for 18 months with a 30-years history of autoimmune disease psoriasis. Computed tomography scan showed a high-density nodule with clear boundaries in the left parotid and multiple enlarged lymph nodes in the left submandibular and neck region. General checkup, the extremely elevated serum interleukin-6 and lymph node biopsy in the left submandibular region gave us an initial suspicion of Castleman's disease. Then the patient underwent a left superficial parotidectomy. Based on histopathologic analysis, we made a certain diagnosis of Castleman's disease and gave corresponding treatments. In 18 months of follow-up, the patient showed no evidence of recurrence, with the level of serum interleukin-6 decreased. CONCLUSIONS: Clinicians should be aware of the possibility of Castleman's disease when faced with masses or enlarged lymph nodes in the parotid gland to avoid misdiagnosis, especially in patients with autoimmune diseases and elevated serum interleukin-6.


Subject(s)
Autoimmune Diseases , Castleman Disease , Lymphadenopathy , Male , Humans , Middle Aged , Castleman Disease/complications , Castleman Disease/diagnosis , Castleman Disease/surgery , Parotid Gland/diagnostic imaging , Parotid Gland/pathology , Interleukin-6 , Biopsy , Neck/pathology , Lymphadenopathy/diagnostic imaging
19.
Acta Pharm Sin B ; 14(4): 1560-1591, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38572104

ABSTRACT

Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i.e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments.

20.
Front Med (Lausanne) ; 11: 1334524, 2024.
Article in English | MEDLINE | ID: mdl-38585148

ABSTRACT

Background: Vitamin D is a crucial fat-soluble vitamin that has garnered significant attention due to its potential impact on respiratory health. It is noteworthy that many patients with chronic obstructive pulmonary disease (COPD) often experience deficiencies or insufficiencies of vitamin D. To address this issue, our retrospective study aimed to explore the potential association between serum 25-hydroxyvitamin D concentration and the prognoses of COPD patients in the Intensive Care Unit (ICU). Methods: This study utilised data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV), a database of patients admitted to the Intensive Care Unit at Beth Israel Deaconess Medical Center (BIDMC) in the United States of America, with a focus on patients with a diagnosis of COPD. These patients were categorized into two groups: those who received vitamin D supplementation during their ICU stay and those who did not. We assessed in-hospital mortality and ICU mortality outcomes. Our analysis involved various analytical tools, including Kaplan-Meier survival curves, Cox proportional risk regression models, and subgroup analyses, to investigate the relationship between vitamin D supplementation and these outcomes. Additionally, we employed propensity-score matching (PSM) to enhance the reliability of our findings. Results: The study included a total of 3,203 COPD patients, with 587 in the vitamin D group and 2,616 in the no-vitamin D group. The Kaplan-Meier survival curve demonstrated a significant difference in survival probability between the two groups. After adjusting for potential confounders using Cox regression models, the vitamin D group exhibited a substantially lower risk of in-hospital and ICU mortalities compared to the no-vitamin D group. The hazard ratios for in-hospital and ICU mortalities in the vitamin D group were 1.7 (95% CI: 1.3, 2.3) and 1.8 (95% CI: 1.2, 2.6), respectively. Propensity-score matching (PSM) estimation yielded consistent results. Furthermore, in the subgroup analysis, female patients who received vitamin D supplementation showed a reduced risk of in-hospital mortality. Conclusion: The study suggests that vitamin D supplementation may be linked to a reduction in in-hospital and ICU mortalities among COPD patients in the ICU. Of particular note is the potential benefit observed in terms of in-hospital mortality, especially for female patients.

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