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1.
Microb Pathog ; 192: 106684, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38759934

ABSTRACT

BACKGROUND: Gut bacteria have an important influence on colorectal cancer (CRC). The differences of gut bacteria between genders have been the hot spots. OBJECTIVE: To analyze the relationship between gut bacteria and gender differences in patients with CRC. METHODS: A total of 212 patients with CRC and 212 healthy volunteers were recruited. The subjects' fecal samples were obtained, and the fecal microorganisms were analyzed by the third-generation sequencing PacBio. The composition of gut bacteria was analyzed. Linear discriminant analysis Effect Size (LEfSe) was used to analyze the differences in gut bacteria. Pearson coefficient was used to calculate the correlation between differential bacteria. CRC risk prediction models were used to rank the importance of effective differential bacteria. RESULTS: Escherichia flexneri and Phocaeicola vulgatus were the most frequent bacteria in both male and female CRC patients. Bacteroides, Verrucomicrobia and Akkermansiaceae were highly enriched in male CRC group, while Bacteroidetes, Phocaeicola and Tissierellales were highly enriched in female CRC group. Peptostreptococcus anaerobius and Phocaeicola vulgatus were important CRC related bacteria in males and females, respectively. Peptostreptococcus anaerobius was the most important characteristic bacterium of males (AUC = 0.951), and the sensitivity and specificity of the discovery set were 78.74 % and 93.98 %, respectively. Blautia stercoris was the most important characteristic bacterium of females (AUC = 0.966), and the sensitivity and specificity of the discovery set were 90.63 % and 90.63 %, respectively. CONCLUSION: Gut bacteria varied in different genders. Therefore, gender should be considered when gut bacteria are applied in the diagnose and prevention of CRC.

2.
Invest Ophthalmol Vis Sci ; 65(5): 14, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38713483

ABSTRACT

Purpose: The purpose of this study was to assess the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on corneal stroma characteristics, ocular manifestations, and post-recovery refractive surgery outcomes after varying recovery durations. Methods: Fresh corneal lenticules from patients with post-coronavirus disease 2019 (COVID-19; recovered within 135 days) and healthy controls (HCs) after small incision lenticule extraction (SMILE) surgery were obtained for experimental validation of SARS-CoV-2 susceptibility, morphological changes, and immune response of the corneal stroma. Corneal optical density (CD) was measured using the Pentacam HR. Corneal epithelium thickness (ET) and endothelium parameters were evaluated by wide-field optical coherence tomography (OCT) and non-contact specular microscopy (SP-1P), respectively. All the patients were assessed after SMILE surgery until 3 month of follow-up. Results: The cornea was susceptible to SARS-CoV-2 with the presence of SARS-CoV-2 receptors (CD147 and ACE2) and spike protein remnants (4 out of 58) in post-recovery corneal lenticules. Moreover, SARS-CoV-2 infection triggered immune responses in the corneal stroma, with elevated IL-6 levels observed between 45 and 75 days post-recovery, which were then lower at around day 105. Concurrently, corneal mid-stromal nerve length and branching were initially higher in the 60D to 75D group and returned to control levels by day 135. A similar trend was observed in CD within zones 0 to 2 and 2 to 6 and in the hexagonal cells (HEX) ratio in endothelial cells, whereas ET remained consistent. Notably, these changes did not affect the efficacy, safety, or predictability of post-recovery SMILE surgery. Conclusions: SARS-CoV-2 induces temporal alterations in corneal stromal morphology and function post-recovery. These findings provided a theoretical basis for corneal health and refractive surgery management in the post-COVID-19 milieu.


Subject(s)
COVID-19 , Corneal Stroma , SARS-CoV-2 , Tomography, Optical Coherence , Humans , Corneal Stroma/pathology , Corneal Stroma/virology , Male , Female , Adult , Tomography, Optical Coherence/methods , Corneal Surgery, Laser/methods , Middle Aged
3.
Biomed Pharmacother ; 176: 116783, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796970

ABSTRACT

During tumor development, the tumor itself must continuously generate new blood vessels to meet their growth needs while also allowing for tumor invasion and metastasis. One of the most common features of tumors is hypoxia, which drives the process of tumor angiogenesis by regulating the tumor microenvironment, thus adversely affecting the prognosis of patients. In addition, to overcome unsuitable environments for growth, such as hypoxia, nutrient deficiency, hyperacidity, and immunosuppression, the tumor microenvironment (TME) coordinates angiogenesis in several ways to restore the supply of oxygen and nutrients and to remove metabolic wastes. A growing body of research suggests that tumor angiogenesis and hypoxia interact through a complex interplay of crosstalk, which is inextricably linked to the TME. Here, we review the TME's positive contribution to angiogenesis from an angiogenesis-centric perspective while considering the objective impact of hypoxic phenotypes and the status and limitations of current angiogenic therapies.

4.
SAGE Open Med Case Rep ; 12: 2050313X241240097, 2024.
Article in English | MEDLINE | ID: mdl-38559411

ABSTRACT

Idiopathic multicentric Castleman disease is a rare and complex disease characterized by systemic inflammation, lymphadenopathy, and multiorgan involvement. This case report presents a 66-year-old Chinese man with idiopathic multicenter Castleman disease without significant lymphadenopathy and challenging diagnosis. Patients present with fever, fatigue, loss of appetite, weight loss, and acute kidney injury. Initially, a urinary tract infection was suspected, but despite anti-infective treatment, the patient's symptoms persisted. Lymph node biopsy, although there is no significant lymphadenopathy, confirms idiopathic multicenter Castleman disease. Treatment includes thalidomide, cyclophosphamide, and dexamethasone, as well as supportive measures and infection control. After 8 months of follow-up, the patient's clinical symptoms, inflammatory markers and renal function were significantly improved, and there was no symptomatic recurrence. This case underscores the importance of considering idiopathic multicenter Castleman's disease in patients with persistent fever and systemic inflammation, even in the absence of significant lymphadenopathy. Early identification and accurate diagnosis of idiopathic multicenter Castleman's disease can lead to the initiation of targeted therapy strategies that ultimately yield favorable outcomes.

5.
BMC Plant Biol ; 24(1): 333, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664694

ABSTRACT

BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.


Subject(s)
Camellia sinensis , Circadian Rhythm , Photosynthesis , Photosynthesis/genetics , Camellia sinensis/genetics , Camellia sinensis/physiology , Circadian Rhythm/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Genes, Plant , Multigene Family , Chlorophyll Binding Proteins/genetics , Chlorophyll Binding Proteins/metabolism , Photoperiod
6.
Clin Transl Med ; 14(5): e1674, 2024 May.
Article in English | MEDLINE | ID: mdl-38685486

ABSTRACT

BACKGROUND: The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. METHODS: A single-arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi-omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Multi-omics analysis was assessed by whole-exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre- and post-neoadjuvant therapy. RESULTS: This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment-emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi-omics analysis correlated with treatment response, highlighting associations between HER2-positive and CTNNB1 mutations with treatment sensitivity and a favourable prognosis. This finding was further supported by immune cell infiltration analysis and mIF. Expression data uncovered a risk model with four genes (RALYL, SCGN, CCKBR, NTS) linked to poor response. Additionally, post-treatment infiltration of CD8+ T lymphocytes positively correlates with pathological response. CONCLUSION: The findings suggest the combination of PD-1-inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow-up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Neoadjuvant Therapy , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Male , Female , Middle Aged , Neoadjuvant Therapy/methods , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , Leucovorin/therapeutic use , Fluorouracil/therapeutic use , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/pharmacology , Treatment Outcome , Multiomics
7.
Genes Dis ; 11(4): 101129, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38545125

ABSTRACT

With the rapid development of histological techniques and the widespread application of single-cell sequencing in eukaryotes, researchers desire to explore individual microbial genotypes and functional expression, which deepens our understanding of microorganisms. In this review, the history of the development of microbial detection technologies was revealed and the difficulties in the application of single-cell sequencing in microorganisms were dissected as well. Moreover, the characteristics of the currently emerging microbial single-cell sequencing (Microbe-seq) technology were summarized, and the prospects of the application of Microbe-seq in microorganisms were distilled based on the current development status. Despite its mature development, the Microbe-seq technology was still in the optimization stage. A retrospective study was conducted, aiming to promote the widespread application of single-cell sequencing in microorganisms and facilitate further improvement in the technology.

8.
Article in English | MEDLINE | ID: mdl-38502350

ABSTRACT

PURPOSE: To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC). METHODS: In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups. RESULTS: The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05). CONCLUSIONS: Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus.

9.
Cancer Med ; 13(6): e7097, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38506253

ABSTRACT

BACKGROUND: Emergence of novel immuno-therapeutics has shown promising improvement in the clinical outcome of colorectal cancer (CRC). OBJECTIVE: To identify robust immune checkpoints based on expression and immune infiltration profiles of clinical CRC samples. METHODS: One dataset from The Cancer Genome Atlas database and two from Gene Expression Omnibus were independently employed for the analysis. Genes associated with overall survival were identified, and distribution of each immune checkpoint with respect to different clinical features was determined to explore key immune checkpoints. Multiple staining methods were used to verify the correlation between key immune checkpoint ICOS and clinical pathological features. Differentially expressed mRNA and long non-coding RNA (lncRNA) were then detected for gene set enrichment analysis and gene set variation analysis to investigate the differentially enriched biological processes between low- and high-expression groups. Significant immune-related mRNAs and lncRNA were subjected to competing endogenous RNA (ceRNA) network analysis. Correlation of inducible T-cell costimulator (ICOS) and top 10 genes in ceRNA network were further considered for validation. RESULTS: ICOS was identified from 14 immune checkpoints as the most highly correlated gene with survival and clinical features in CRC. The expression of ICOS protein in the poorly differentiated group was lower than that in the moderately differentiated group, and the expression in different pathological stages was significant. In addition, the expressions of ICOS were negatively correlated with Ki67. A conspicuous number of immune-related pathways were enriched in differentially expressed genes in the ICOS high- and low-expression groups. Integration with immune infiltration data revealed a multitude of differentially expressed immune-related genes enriched for ceRNA network. Furthermore, expression of top 10 genes investigated from ceRNA network showed high correlation with ICOS. CONCLUSION: ICOS might serve as a robust immune checkpoint for prognosis with several genes being potential targets of ICOS-directed immunotherapy in CRC.


Subject(s)
Colorectal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Immune Checkpoint Proteins/genetics , RNA, Long Noncoding/genetics , Cell Differentiation , Colorectal Neoplasms/genetics , T-Lymphocytes
10.
Plant J ; 118(5): 1312-1326, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38319894

ABSTRACT

Lignin is an important component of plant cell walls and plays crucial roles in the essential agronomic traits of tea quality and tenderness. However, the molecular mechanisms underlying the regulation of lignin biosynthesis in tea plants remain unclear. CsWRKY13 acts as a negative regulator of lignin biosynthesis in tea plants. In this study, we identified a GRAS transcription factor, phytochrome A signal transduction 1 (CsPAT1), that interacts with CsWRKY13. Silencing CsPAT1 expression in tea plants and heterologous overexpression in Arabidopsis demonstrated that CsPAT1 positively regulates lignin accumulation. Further investigation revealed that CsWRKY13 directly binds to the promoters of CsPAL and CsC4H and suppresses transcription of CsPAL and CsC4H. CsPAT1 indirectly affects the promoter activities of CsPAL and CsC4H by interacting with CsWRKY13, thereby facilitating lignin biosynthesis in tea plants. Compared with the expression of CsWRKY13 alone, the co-expression of CsPAT1 and CsWRKY13 in Oryza sativa significantly increased lignin biosynthesis. Conversely, compared with the expression of CsPAT1 alone, the co-expression of CsPAT1 and CsWRKY13 in O. sativa significantly reduced lignin accumulation. These results demonstrated the antagonistic regulation of the lignin biosynthesis pathway by CsPAT1 and CsWRKY13. These findings improve our understanding of lignin biosynthesis mechanisms in tea plants and provide insights into the role of the GRAS transcription factor family in lignin accumulation.


Subject(s)
Camellia sinensis , Gene Expression Regulation, Plant , Lignin , Plant Proteins , Transcription Factors , Lignin/metabolism , Lignin/biosynthesis , Transcription Factors/metabolism , Transcription Factors/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Camellia sinensis/genetics , Camellia sinensis/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Plants, Genetically Modified , Promoter Regions, Genetic/genetics
11.
Adv Mater ; 36(16): e2311970, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38198824

ABSTRACT

[4-(3,6-dimethyl-9H-carbazol-9yl)butyl]phosphonic acid (Me-4PACz) self-assembled molecules (SAM) are an effective method to solve the problem of the buried interface of NiOx in inverted perovskite solar cells (PSCs). However, the Me-4PACz end group (carbazole core) cannot forcefully passivate defects at the bottom of the perovskite film. Here, a Co-SAM strategy is employed to modify the buried interface of PSCs. Me-4PACz is doped with phosphorylcholine chloride (PC) to form a Co-SAM to improve the monolayer coverage and reduce leakage current. The phosphate group and chloride ions (Cl-) in PC can inhibit NiOx surface defects. Meantime, the quaternary ammonium ions and Cl- in PC can fill organic cations and halogen vacancies in the perovskite film to enable defects passivation. Moreover, Co-SAM can promote the growth of perovskite crystals, collaboratively solve the problem of buried defects, suppress nonradiative recombination, accelerate carrier transmission, and relieve the residual stress of the perovskite film. Consequently, the Co-SAM modified devices show power conversion efficiencies as high as 25.09% as well as excellent device stability with 93% initial efficiency after 1000 h of operation under one-sun illumination. This work demonstrates the novel approach for enhancing the performance and stability of PSCs by modifying Co-SAM on NiOx.

12.
Transl Vis Sci Technol ; 13(1): 14, 2024 01 02.
Article in English | MEDLINE | ID: mdl-38231497

ABSTRACT

Purpose: To assess changes in corneal epithelial thickness (ET) within 9-mm diameter cornea after photorefractive keratectomy (PRK) retreatment after small-incision lenticule extraction (SMILE). Methods: A total of 28 eyes of 19 patients with mean spherical equivalent of -1.30 ± 0.60 D who underwent retreatment after SMILE were included in this retrospective study. ET mapped across a 9-mm diameter area was obtained using wide-field optical coherence tomography (OCT) before and at one, three, and six months after surgery. The ET changes were compared between the different time points and analyzed zones. Results: Before enhancement, the ET were 63.64 ± 6.01 µm and 61.25 ± 4.32 µm in central and paracentral zones, respectively. The ET of central and paracentral zones significantly decreased at one month and subsequently increased until six months. Six months after surgery, significant epithelial thickening occurred in 2- to 9-mm diameter cornea (all P < 0.05), whereas no significant change was observed in central 2-mm diameter cornea (P = 0.460). There was no significant difference in the ET between the central and paracentral zones (P = 1.00). The degree of myopic correction significantly correlated with the average ET in the central (P = 0.046) and paracentral (P = 0.033) zones at six months after PRK enhancement. No significant correlation was detected between the average ET of all zones and the postoperative spherical equivalent at six months after surgery (all P > 0.05). Conclusions: PRK enhancement did not alter the overall trend of corneal epithelial remodeling induced by SMILE. An asymmetric and flatter lenticule-like pattern of epithelial remodeling was observed six months after surgery, which did not affect the refractive outcomes. Translational Relevance: An asymmetric and centrally flattened lenticule-like pattern of epithelial remodeling was observed after PRK enhancement. Surgeons should consider expanding the intended optical zones for enhancement surgery after SMILE.


Subject(s)
Myopia , Photorefractive Keratectomy , Humans , Retrospective Studies , Cornea/surgery , Myopia/surgery , Refraction, Ocular
13.
Int J Mol Sci ; 25(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38203827

ABSTRACT

The circadian clock refers to the formation of a certain rule in the long-term evolution of an organism, which is an invisible 'clock' in the body of an organism. As one of the largest TF families in higher plants, the MYB transcription factor is involved in plant growth and development. MYB is also inextricably correlated with the circadian rhythm. In this study, the transcriptome data of the tea plant 'Baiyeyihao' were measured at a photoperiod interval of 4 h (24 h). A total of 25,306 unigenes were obtained, including 14,615 unigenes that were annotated across 20 functional categories within the GO classification. Additionally, 10,443 single-gene clusters were annotated to 11 sublevels of metabolic pathways using KEGG. Based on the results of gene annotation and differential gene transcript analysis, 22 genes encoding MYB transcription factors were identified. The G10 group in the phylogenetic tree had 13 members, of which 5 were related to the circadian rhythm, accounting for 39%. The G1, G2, G8, G9, G15, G16, G18, G19, G20, G21 and G23 groups had no members associated with the circadian rhythm. Among the 22 differentially expressed MYB transcription factors, 3 members of LHY, RVE1 and RVE8 were core circadian rhythm genes belonging to the G10, G12 and G10 groups, respectively. Real-time fluorescence quantitative PCR was used to detect and validate the expression of the gene transcripts encoding MYB transcription factors associated with the circadian rhythm.


Subject(s)
Camellia sinensis , Circadian Clocks , Humans , Camellia sinensis/genetics , Phylogeny , Circadian Rhythm/genetics , Tea
14.
Mol Med ; 30(1): 10, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38216878

ABSTRACT

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.


Subject(s)
Melatonin , Osteoporosis , Animals , Mice , Osteogenesis , Osteoclasts/metabolism , Melatonin/pharmacology , Reactive Oxygen Species , Antioxidants/pharmacology , Oxidation-Reduction , Homeostasis , Cell Differentiation , NF-kappa B/metabolism
15.
Aging (Albany NY) ; 16(2): 1298-1317, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38244586

ABSTRACT

BACKGROUND: Cisplatin is a core chemotherapy regimen in non-small cell lung cancer (NSCLC). However, chemoresistance to cisplatin leads to a poor prognosis in NSCLC. α-Hederin is a natural compound extracted from Nigella sativa. The study aims to explore the effects of α-Hederin on cisplatin resistance in NSCLC. METHODS: NSCLC cisplatin-resistant cell lines A549/DPP and PC-9 were cultured to evaluate the efficacy of α-Hederin in the treatment of NSCLC in vitro and in vivo. Metabolomics and RNA-seq analysis were used to determine the potential mechanisms of action of α-Hederin. RESULTS: The results showed that α-Hederin inhibited cisplatin-resistant NSCLC cells proliferation and metastasis. Mice xenograft, orthotopic, and metastatic A549/DPP cell models also showed the anti-tumor effects of α-Hederin. The metabolomics and RNA-seq analysis results showed that α-Hederin activated DDIT3/ATF3 pathway and ferroptosis via silencing SLC7A11 and GPX4. Furthermore, α-Hederin enhanced the nuclear expression of EGR1. Bioinformatics and luciferase experiments confirmed that EGR1 binds to the miR-96-5p promoter region, inhibiting transcription. In addition, miR-96-5p directly suppressed the levels of DDIT3. CONCLUSION: This study revealed that α-Hederin activated EGR1 nuclear translocation and directly repressed miR-96-5p. It also promoted DDIT3/ATF3-mediated ferroptosis and reversed cisplatin resistance in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Ferroptosis , Lung Neoplasms , MicroRNAs , Saponins , Humans , Animals , Mice , Carcinoma, Non-Small-Cell Lung/genetics , Cisplatin/pharmacology , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Drug Resistance, Neoplasm , MicroRNAs/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation
16.
Arch Biochem Biophys ; 753: 109904, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38253247

ABSTRACT

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.


Subject(s)
Abietanes , Cartilage, Articular , Osteoarthritis , Mice , Animals , Vascular Endothelial Growth Factor A , Endothelial Cells/metabolism , Angiogenesis , Osteoarthritis/metabolism
17.
Digestion ; 105(2): 107-130, 2024.
Article in English | MEDLINE | ID: mdl-37995661

ABSTRACT

INTRODUCTION: Endoplasmic reticulum stress (ERS) is associated with the occurrence and development of colorectal cancer (CRC). METHODS: One thousand nine CRC samples and 3 ERS gene sets from GEO database were used to screen and validate genes related to stage and prognosis of CRC. Twenty thousand five hundred thirty samples from the TCGA database validated the ERS genes related to prognosis. PPI network construction and coexpression analysis were used to investigate the correlation of genes. ConsensusClusterPlus analysis was used to classify CRC subtypes. Cox regression and the LASSO algorithm were used to screen ERS genes related to prognosis. HE staining, immunohistochemical staining, and RT-qPCR of 50 owner-central samples were used to verify the genes. The ERscore model was constructed based on the ERS genes related to prognosis. The nomogram model was used to verify that different subtypes of CRC patients have different prognosis. RESULTS: Fifty ERS differentially expressed genes related to CRC stage and 8 ERS model genes related to prognosis were screened. Three subtypes of CRC were classified based on the former 50 genes. The clinical characteristics were significantly different among the subtypes. The ERscore model was constructed based on the latter 8 genes, and its accuracy was verified by clinical samples. Finally, the nomogram was constructed based on ERscore, age, and CRC stage, and the accuracy of the nomogram prediction was verified. CONCLUSION: ERS-related genes can be used as classification criteria for CRC, and the related clinical characteristics of different CRC subtypes are different.


Subject(s)
Colorectal Neoplasms , Nomograms , Humans , Databases, Factual , Endoplasmic Reticulum Stress/genetics , Colorectal Neoplasms/genetics , Prognosis
18.
Dig Dis Sci ; 69(1): 123-134, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37917212

ABSTRACT

BACKGROUND: Bile acids (BAs) are closely related to the occurrence and development of colorectal cancer (CRC), but the specific mechanism is still unclear. AIMS: To identify potential targets related to BAs in CRC and analyze the correlation with immunity. METHODS: The expression of BAs and CRC-related genes in TCGA was studied and screened using KEGG. GSE71187 was used for external validation of differentially expressed genes. Immunofluorescence, immunohistochemistry, and enzymatic cycling assays were used to detect the expression levels of the differentially expressed genes ki67 and BAs. Weighted gene coexpression network analysis (WGCNA) was used to identify genes associated with differential gene expression and immunity. The Cibersort algorithm was used to detect the infiltration of 22 kinds of immune cells in cancer tissues. The PPI network and ceRNA network were constructed to reveal the possible molecular mechanisms behind tumorigenesis. RESULTS: The BA-related gene UGT2A3 is positively correlated with good prognoses in CRC. The expression level of UGT2A3 was negatively related to the BA level and positively related to the Ki67 proliferation index. The expression level of UGT2A3 was higher in the moderately differentiation and advanced stage (stage IV) of CRC. In addition, the expression level of UGT2A3 is correlated with CD8+ T cells. A PPI network related to UGT2A3 and T-cell immune-related genes was constructed. A ceRNA network containing 32 miRNA‒mRNA and 40 miRNA‒lncRNA regulatory pairs was constructed. CONCLUSION: UGT2A3 is a potential molecular target of bile acids in the regulation of CRC and is related to T-cell immunity.


Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , Bile Acids and Salts , Ki-67 Antigen , Algorithms , Colorectal Neoplasms/genetics
19.
Adv Mater ; 36(6): e2309869, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38014776

ABSTRACT

Blade coating has been developed to be an essential technique for large-area fabrication of perovskite solar cells (PSCs). However, effective surface treatment of the perovskite layer, which is a critical step for improving PSC performance, remains challenges during blade coating due to the short interaction time between the modification solution and the perovskite layer, as well as the limited selection of available organic solvents. In this study, a novel modifier N,N-diphenylguanidine monohydrobromide (DPGABr) dissolved in acetonitrile (ACN) is blade coated on the MA0.7 FA0.3 PbI3 surface in air to reconstruct the perovskite surface in hundreds of milliseconds. This work finds that the solvent ACN rapidly dissolves organic iodide of the perovskite layer and leads to a PbI2 -rich surface, providing reactive sites for DPGABr to form a thin DPGABr/PbI2 complex layer. This surface reconstruction can effectively passivate defects and induce n-type doping on the perovskite surface to facilitate electron transfer. The resultant devices show a 15% improvement in average power conversion efficiency. More importantly, the devices with the surface reconstruction show outstanding long-term stability, with negligible performance degradation even after 1-year storage in air. This study presents a convenient and effective approach for improving the performance of blade-coated PSCs prepared in air.

20.
Br J Surg ; 111(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-37943801

ABSTRACT

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.


Subject(s)
Colonic Neoplasms , Laparoscopy , Humans , Anastomotic Leak/epidemiology , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Cohort Studies , Prospective Studies , Blood Loss, Surgical , Colonic Neoplasms/pathology , Colectomy/adverse effects , Colectomy/methods , Morbidity , Risk Factors , Laparoscopy/adverse effects , Laparoscopy/methods , Retrospective Studies
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