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1.
Front Chem ; 12: 1447831, 2024.
Article in English | MEDLINE | ID: mdl-39119517

ABSTRACT

In this work, a series of new diarylpyrimidine derivatives as microtubule destabilizers were designed, synthesized, and evaluated for anticancer activities. Based on restriction configuration strategy, we introduced the pyrimidine moiety containing the hydrogen-bond acceptors as cis-olefin bond of CA-4 analogs to improve structural stability. Compounds 11a-t exerted antiproliferative activities against three human cancer cell lines (SGC-7901, HeLa, and MCF-7), due to tubulin polymerization inhibition, showing high selectivity toward cancer cells in comparison with non-tumoral HSF cells, as evidenced by MTT assays. In mechanistic investigations, compound 11s remarkably inhibited tubulin polymerization and disorganized microtubule in SGC-7901 cells by binding to tubulin. Moreover, 11s caused G2/M phase cell cycle arrest in SGC-7901 cells in a concentration-dependent manner. Furthermore, molecular modeling analysis revealed that 11s interacts with tubulin through binding to the colchicine site. In addition, the prediction of physicochemical properties disclosed that 11s conformed well to the Lipinski's rule of five. This work offered a fresh viewpoint for the discovery of new tubulin-targeting anticancer drugs.

2.
Nat Commun ; 15(1): 6737, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112475

ABSTRACT

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.


Subject(s)
Acute Lung Injury , Cell Movement , Interleukin-17 , Lung , Mice, Inbred C57BL , Sepsis , Animals , Sepsis/immunology , Sepsis/complications , Acute Lung Injury/immunology , Acute Lung Injury/pathology , Mice , Interleukin-17/metabolism , Interleukin-17/immunology , Lung/immunology , Lung/pathology , Male , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Wnt Signaling Pathway/immunology , Macrophages, Alveolar/immunology , Intestine, Small/immunology , Intestine, Small/pathology , Intraepithelial Lymphocytes/immunology , Disease Models, Animal , Antigens, Ly/metabolism , Immunologic Memory
3.
ACS Nano ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39141682

ABSTRACT

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by arterial intimal lipid plaques. Small interfering ribonucleic acid (siRNA)-based therapies, with their ability to suppress specific genes with high targeting precision and minimal side effects, have shown great potential for AS treatment. However, targets of siRNA therapies based on macrophages for AS treatment are still limited. Olfactory receptor 2 (Olfr2), a potential target for plaque formation, was discovered recently. Herein, anti-Olfr2 siRNA (si-Olfr2) targeting macrophages was designed, and the theranostic platform encapsulating si-Olfr2 to target macrophages within atherosclerotic lesions was also developed, with the aim of downregulating Olfr2, as well as diagnosing AS through photoacoustic imaging (PAI) in the second near-infrared (NIR-II) window with high resolution. By utilization of a reactive oxygen species (ROS)-responsive nanocarrier system, the expression of Olfr2 on macrophages within atherosclerotic plaques was effectively downregulated, leading to the inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 ß (IL-1ß) secretion, thereby reducing the formation of atherosclerotic plaques. As manifested by decreased Olfr2 expression, the lesions exhibited a significantly alleviated inflammatory response that led to reduced lipid deposition, macrophage apoptosis, and a noticeable decrease in the necrotic areas. This study provides a proof of concept for evaluating the theranostic nanoplatform to specifically deliver si-Olfr2 to lesional macrophages for AS diagnosis and treatment.

4.
JCI Insight ; 9(16)2024 08 22.
Article in English | MEDLINE | ID: mdl-39171524

ABSTRACT

Decidual regulatory T cells (Tregs) are essential for successful pregnancy outcome. A subset of Tregs, T cell immunoglobulin and mucin domain-containing protein 3-positive regulatory T cells (TregsTim-3+), plays a central role in the acceptance of the fetus during early stages of normal pregnancy. The molecular mechanism regulating the differentiation and function of TregsTim-3+ is unknown. Here, we investigated the role of the transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) on decidual TregTim-3+ differentiation. We demonstrated that Blimp-1 enhanced the coexpression of negative costimulatory molecules (Tim-3, T cell immunoreceptor with Ig and ITIM domains, and programmed cell death protein 1) on Tregs and improved their immunosuppressive functions, including increased IL-10 secretion, suppression of effector T cell proliferation, and promotion of macrophage polarization toward the M2 phenotype. Furthermore, we showed that IL-27 regulated the expression of Tim-3 and Blimp-1 through the STAT1 signaling pathway and that transfer of TregsBlimp-1+ into an abortion-prone mouse model effectively reduced embryo absorption rate. We postulated that abnormalities in the IL-27/Blimp-1 axis might be associated with recurrent pregnancy loss (RPL). These findings provided insights for developing more efficient immunotherapies for women with RPL.


Subject(s)
Cell Differentiation , Hepatitis A Virus Cellular Receptor 2 , Positive Regulatory Domain I-Binding Factor 1 , T-Lymphocytes, Regulatory , Female , Animals , Pregnancy , Positive Regulatory Domain I-Binding Factor 1/metabolism , Positive Regulatory Domain I-Binding Factor 1/genetics , Hepatitis A Virus Cellular Receptor 2/metabolism , Mice , Cell Differentiation/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , STAT1 Transcription Factor/metabolism , Signal Transduction , Humans , Decidua/immunology , Decidua/metabolism , Decidua/cytology , Interleukin-10/metabolism , Interleukins/metabolism , Interleukins/immunology , Interleukin-27/metabolism
5.
Nutr Metab (Lond) ; 21(1): 67, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160585

ABSTRACT

Methionine, an indispensable amino acid crucial for dietary balance, intricately governs metabolic pathways. Disruption in its equilibrium has the potential to heighten homocysteine levels in both plasma and tissues, posing a conceivable risk of inducing inflammation and detriment to the integrity of vascular endothelial cells. The intricate interplay between methionine metabolism, with a specific focus on S-adenosyl-L-methionine (SAM), and the onset of thoracic aortic dissection (TAD) remains enigmatic despite acknowledging the pivotal role of inflammation in this vascular condition. In an established murine model induced by ß-aminopropionitrile monofumarate (BAPN), we delved into the repercussions of supplementing with S-adenosyl-L-methionine (SAM) on the progression of TAD. Our observations uncovered a noteworthy improvement in aortic dissection and rupture rates, accompanied by a marked reduction in mortality upon SAM supplementation. Notably, SAM supplementation exhibited a considerable protective effect against BAPN-induced degradation of elastin and the extracellular matrix. Furthermore, SAM supplementation demonstrated a robust inhibitory influence on the infiltration of immune cells, particularly neutrophils and macrophages. It also manifested a notable reduction in the inflammatory polarization of macrophages, evident through diminished accumulation of MHC-IIhigh macrophages and reduced expression of inflammatory cytokines such as IL1ß and TNFα in macrophages. Simultaneously, SAM supplementation exerted a suppressive effect on the activation of CD4 + and CD8 + T cells within the aorta. This was evidenced by an elevated proportion of CD44- CD62L + naïve T cells and a concurrent decrease in CD44 + CD62L- effector T cells. In summary, our findings strongly suggest that the supplementation of SAM exhibits remarkable efficacy in alleviating BAPN-induced aortic inflammation, consequently impeding the progression of thoracic aortic dissection.

6.
Small ; : e2404199, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949393

ABSTRACT

The performance of perovskite solar cells has been continuously improving. However, humidity stability has become a key problem that hinders its promotion in the process of commercialization. A buffer layer deposited by atomic layer deposition is a very helpful method to solve this problem. In this work, MgO film is deposited between Spiro-OMeTAD and electrode by low-temperature atomic layer deposition at 80 °C, which resists the erosion of water vapor, inhibits the migration of electrode metal ions and the decomposition products of perovskite, then finally improves the stability of the device. At the same time, the MgO buffer layer can passivate the defects of porous Spiro, thus enhancing carrier transport efficiency and device performance. The Cs0.05(FAPbI3)0.85(MAPbBr3)0.15 perovskite device with a MgO buffer layer has displayed PCE of 22.74%, also with a high Voc of 1.223 V which is an excellent performance in devices with same perovskite component. Moreover, the device with a MgO buffer layer can maintain 80% of the initial efficiency after 7200 h of storage at 35% relative humidity under room temperature. This is a major achievement for humidity stability in the world, providing more ideas for further improving the stability of perovskite devices.

7.
J Natl Cancer Cent ; 4(1): 86-92, 2024 Mar.
Article in English | MEDLINE | ID: mdl-39036380

ABSTRACT

Background: Approximately 10%-30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9-46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2-23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

8.
Front Immunol ; 15: 1434688, 2024.
Article in English | MEDLINE | ID: mdl-39040114

ABSTRACT

Sepsis is described as a life-threatening organ dysfunction and a heterogeneous syndrome that is a leading cause of morbidity and mortality in intensive care settings. Severe sepsis could incite an uncontrollable surge of inflammatory cytokines, and the host immune system's immunosuppression could respond to counter excessive inflammatory responses, characterized by the accumulated anti-inflammatory cytokines, impaired function of immune cells, over-proliferation of myeloid-derived suppressor cells and regulatory T cells, depletion of immune effector cells by different means of death, etc. In this review, we delve into the underlying pathological mechanisms of sepsis, emphasizing both the hyperinflammatory phase and the associated immunosuppression. We offer an in-depth exploration of the critical mechanisms underlying sepsis, spanning from individual immune cells to a holistic organ perspective, and further down to the epigenetic and metabolic reprogramming. Furthermore, we outline the strengths of artificial intelligence in analyzing extensive datasets pertaining to septic patients, showcasing how classifiers trained on various clinical data sources can identify distinct sepsis phenotypes and thus to guide personalized therapy strategies for the management of sepsis. Additionally, we provide a comprehensive summary of recent, reliable biomarkers for hyperinflammatory and immunosuppressive states, facilitating more precise and expedited diagnosis of sepsis.


Subject(s)
Sepsis , Humans , Sepsis/immunology , Animals , Biomarkers , Cytokines/metabolism , Cytokines/immunology , Immune Tolerance
9.
World J Clin Cases ; 12(19): 3692-3700, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38994290

ABSTRACT

BACKGROUND: Dietary fiber is essential for human health and can help reduce the symptoms of constipation. However, the relationship between dietary fiber and diarrhea is, poorly understood. AIM: To evaluate the relationship between dietary fiber and chronic diarrhea. METHODS: This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey, conducted between 2005 and 2010. Participants over the age of 20 were included. To measure dietary fiber consumption, two 24-hour meal recall interviews were conducted. The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis. RESULTS: Data from 12829 participants were analyzed. Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea (29.7 vs 28.5, P = 0.004). Additionally, in participants with chronic diarrhea, a correlation between sex and dietary fiber intake was present: Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea. CONCLUSION: Dietary fiber can reduce the occurrence of chronic diarrhea.

10.
Case Rep Cardiol ; 2024: 3766536, 2024.
Article in English | MEDLINE | ID: mdl-39015672

ABSTRACT

Frank's sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient's chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.

11.
J Food Sci ; 89(8): 4899-4913, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38980988

ABSTRACT

Nonenzymatic glycosylation of proteins can generate advanced glycosylation end products, which are closely associated with the pathogenesis of certain chronic physiological diseases and aging. In this study, we characterized the covalent binding of cyanidin-3-glucoside (C3G) to bovine serum albumin (BSA) and investigated the mechanism by which this covalent binding inhibits the nonenzymatic glycosylation of BSA. The results indicated that the covalent interaction between C3G and BSA stabilized the protein's secondary structure. Through liquid chromatography-electrospray ionization tandem mass spectrometry analysis, we identified the covalent binding sites of C3G on BSA as lysine, arginine, asparagine, glutamine, and cysteine residues. This covalent interaction significantly suppressed the nonenzymatic glycosylation of BSA, consequently reducing the formation of nonenzymatic glycosylation products. C3G competitively binds to nonenzymatic glycosylation sites (e.g., lysine and arginine) on BSA, thereby impeding the glycosylation process and preventing the misfolding and structural alterations of BSA induced by fructose. Furthermore, the covalent attachment of C3G to BSA preserves the secondary structure of BSA and hinders subsequent nonenzymatic glycosylation events.


Subject(s)
Anthocyanins , Glucosides , Serum Albumin, Bovine , Glycosylation , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/metabolism , Anthocyanins/chemistry , Anthocyanins/metabolism , Glucosides/metabolism , Glucosides/chemistry , Animals , Binding Sites , Cattle , Protein Structure, Secondary , Glycation End Products, Advanced/chemistry , Glycation End Products, Advanced/metabolism , Protein Binding , Tandem Mass Spectrometry , Spectrometry, Mass, Electrospray Ionization
12.
Nanomaterials (Basel) ; 14(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38998712

ABSTRACT

Magnetic metal absorbing materials have exhibited excellent absorptance performance. However, their applications are still limited in terms of light weight, low thickness and wide absorption bandwidth. To address this challenge, we design a broadband and low-profile multilayer absorber using cobalt-iron (CoFe) alloys doped with rare earth elements (REEs) lanthanum (La) and Neodymium (Nd). An improved estimation of distribution algorithm (IEDA) is employed in conjunction with a mathematical model of multilayer absorbing materials (MAMs) to optimize both the relative bandwidth with reflection loss (RL) below -10 dB and the thickness. Firstly, the absorption performance of CoFe alloys doped with La/Nd with different contents is analysed. Subsequently, IEDA is introduced based on a mathematical model to achieve an optimal MAM design that obtains a balance between absorption bandwidth and thickness. To validate the feasibility of our proposed method, a triple-layer MAM is designed and optimized to exhibit wide absorption bandwidth covering C, X, and Ku bands (6.16-12.82 GHz) and a total thickness of 2.39 mm. Then, the electromagnetic (EM) absorption mechanisms of the triple-layer MAMs are systematically investigated. Finally, the triple-layer sample is further fabricated and measured. The experimental result is in good agreement with the simulated result. This paper presents a rapid and efficient optimization method for designing MAMs, offering promising prospects in microwave applications, such as radar-stealth technology, EM shielding, and reduced EM pollution for electronic devices.

13.
BMC Gastroenterol ; 24(1): 237, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075373

ABSTRACT

BACKGROUND: The research aims to explore the characteristics of intestinal flora, nutritional status and immune function in patients with different types of obese colon cancer. METHODS: A retrospective analysis is conducted on 64 cases of obese colon cancer diagnosed from June 2018 to January 2020. According to the histological staging of the cancer, they are classified into adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma, with corresponding cases of 24, 22 and 18, respectively. The intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI), immune function (IgG, IgM, IgA, CD4+, CD8+, and CD4+/CD8+) are analyzed in the different groups of patients. Survival curves are evaluated by Kaplan-Meier method and log-rank test for tumour death, local recurrence, and distant metastasis. RESULTS: There were no statistically significant differences in intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI) and immune function (IgG, IgM, IgA, CD4+, CD8+, and CD4+/CD8+) between different groups. There was a significant correlation between intestinal flora, nutritional status and immune function for all three. The survival curves of tumour death, local recurrence and distant metastasis in different groups of obese colon cancer patients were statistically significant. The tumor mortality rate, local recurrence, and distant metastasis rate in adenocarcinoma were 78.65%, 54.25% and 48.26% respectively. CONCLUSION: There are differences in intestinal flora, nutritional status and immune function among different types of obese colon cancer patients, but adenocarcinoma has the least benefit in intestinal flora, poor nutritional status, and weakest immune function.


Subject(s)
Colonic Neoplasms , Gastrointestinal Microbiome , Nutritional Status , Obesity , Humans , Gastrointestinal Microbiome/immunology , Male , Female , Middle Aged , Retrospective Studies , Colonic Neoplasms/immunology , Colonic Neoplasms/microbiology , Colonic Neoplasms/pathology , Obesity/complications , Obesity/immunology , Aged , Adenocarcinoma/immunology , Adenocarcinoma/microbiology , Adenocarcinoma/pathology , Adult
14.
Comput Biol Med ; 179: 108844, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38981214

ABSTRACT

This review delves into the burgeoning field of explainable artificial intelligence (XAI) in the detection and analysis of lung diseases through vocal biomarkers. Lung diseases, often elusive in their early stages, pose a significant public health challenge. Recent advancements in AI have ushered in innovative methods for early detection, yet the black-box nature of many AI models limits their clinical applicability. XAI emerges as a pivotal tool, enhancing transparency and interpretability in AI-driven diagnostics. This review synthesizes current research on the application of XAI in analyzing vocal biomarkers for lung diseases, highlighting how these techniques elucidate the connections between specific vocal features and lung pathology. We critically examine the methodologies employed, the types of lung diseases studied, and the performance of various XAI models. The potential for XAI to aid in early detection, monitor disease progression, and personalize treatment strategies in pulmonary medicine is emphasized. Furthermore, this review identifies current challenges, including data heterogeneity and model generalizability, and proposes future directions for research. By offering a comprehensive analysis of explainable AI features in the context of lung disease detection, this review aims to bridge the gap between advanced computational approaches and clinical practice, paving the way for more transparent, reliable, and effective diagnostic tools.


Subject(s)
Artificial Intelligence , Biomarkers , Lung Diseases , Humans , Lung Diseases/diagnosis , Biomarkers/metabolism
16.
Aesthetic Plast Surg ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38914881

ABSTRACT

Epigenetic alterations of non-coding RNA (ncRNA) are pivotal in the continuous activation and differentiation of fibroblasts in keloid. However, the epigenetic mechanism of circRNA in keloid is still not clear yet. In this study, we aimed to investigate the interplay among differentially expressed circRNAs, miRNAs, and mRNAs during wound healing in keloid-prone individuals, construct a competing endogenous RNA (ceRNA) network, and gain an in-depth insight into the pathophysiological mechanisms underlying keloid development. Utilizing bioinformatic methods, we analyzed the expression profiles from the GSE113621 database. We identified 29 differentially expressed circRNAs (DEcircRNAs) in keloid-prone individuals during wound healing, from which we constructed 14 ceRNA networks. Subsequently, we validated the expression of predicted DEcircRNAs in keloid tissues and elucidated the ceRNA network involving circ_064002 and fibronectin-1 (FN1) through competing miR-30a/b-5p. Knocking down circ_064002 led to down-regulation of FN1 expression and various cellular functions in keloid-derived fibroblasts (KFs), including cell viability, migration, invasion, and repair capacity. Our study introduces a novel approach to explore the presence of DEcircRNAs and the ceRNA regulatory network during wound healing in keloid-prone individuals through in-depth mining of GEO data and also proves the epigenetic regulatory mechanism of circ_064002 in KFs. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

17.
Orthop Surg ; 16(8): 1884-1892, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38887157

ABSTRACT

OBJECTIVE: Surgical site infection (SSI) after spinal surgery is still a persistent worldwide health concern as it is a worrying and devastating complication. The number of samples in previous studies is limited and the role of conservative antibiotic therapy has not been established. This study aims to evaluate the clinical efficacy and feasibility of empirical antibiotic treatment for suspected early-onset deep spinal SSI. METHODS: We conducted a retrospective study to identify all cases with suspected early-onset deep SSI after lumbar instrumented surgery between January 2009 and December 2018. We evaluated the potential risks for antibiotic treatment, examined the antibiotic treatment failure rate, and applied logistic regression analysis to assess the risk factors for empirical antibiotic treatment failure. RESULTS: Over the past 10 years, 45 patients matched the inclusion criteria. The success rate of antibiotic treatment was 62.2% (28/45). Of the 17 patients who failed antibiotic treatment, 16 were cured after a debridement intervention and the remaining one required removal of the internal fixation before recovery. On univariate analysis, risk factors for antibiotic treatment failure included age, increasing or persisting back pain, wound dehiscence, localized swelling, and time to SSI (cut-off: 10 days). Multivariate analysis revealed that infection occurring 10 days after primary surgery and wound dehiscence were independent risk factors for antibiotic treatment failure. CONCLUSION: Appropriate antibiotic treatment is an alternative strategy for suspected early-onset deep SSI after lumbar instrumented surgery. Antibiotic treatment for suspected SSI occurring within 10 days after primary surgery may improve the success rate of antibiotic intervention. Patients with wound dehiscence have a significantly higher likelihood of requiring surgical intervention.


Subject(s)
Anti-Bacterial Agents , Lumbar Vertebrae , Surgical Wound Infection , Humans , Retrospective Studies , Surgical Wound Infection/etiology , Male , Female , Middle Aged , Anti-Bacterial Agents/therapeutic use , Lumbar Vertebrae/surgery , Aged , Adult , Risk Factors , Treatment Failure , Debridement
18.
Arch Biochem Biophys ; 758: 110072, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38914215

ABSTRACT

The role of fat mass and obesity-associated protein (FTO)-mediated N6-methyladenosine (m6A)-demethylation has been investigated in various types of cancers, but it is still unclear whether FTO participates in the progression of diffuse large B-cell lymphoma (DLBCL). Here, by conducting Real-Time qPCR and Western Blot analysis, we verified that FTO was especially enriched in the DLBCL cells (RCK-8, LY-3, DHL-6 and U2932) compared to normal WIL2S cells. Then, the overexpression and silencing vectors for FTO were delivered into the LY-3 and U2932 cells, and our functional experiments confirmed that silencing of FTO suppressed cell viability and division, and induced apoptotic cell death in the DLBCL cells, whereas FTO-overexpression exerted opposite effects. Further mechanical experiments showed that FTO demethylated m6A modifications in flotillin-2 (FLOT2) mRNA to sustain its stability for FLOT2 upregulation, and elevated FLOT2 subsequently increased the expression levels of phosphorylated PI3K (p-PI3K), p-Akt and p-mTOR to activate the tumor-initiating PI3K/Akt/mTOR signal pathway. Of note, FLOT2 also serve as an oncogene to enhance cancer malignancy in DLBCL, and the rescuing experiments showed that FTO-ablation induced suppressing effects on the malignant phenotypes in DLBCL were all abrogated by overexpressing FLOT2. Taken together, those data hinted that FTO-mediated m6A-demethylation upregulated FLOT2 to activate the downstream PI3K/Akt/mTOR signal pathway, leading to the aggressiveness of DLBCL, which potentially provided diagnostic, therapeutic and prognostic biomarkers for DLBCL.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO , Lymphoma, Large B-Cell, Diffuse , Membrane Proteins , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Up-Regulation , Humans , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Proto-Oncogene Proteins c-akt/metabolism , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Membrane Proteins/metabolism , Membrane Proteins/genetics , TOR Serine-Threonine Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Apoptosis
19.
World J Gastroenterol ; 30(19): 2603-2611, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38817661

ABSTRACT

BACKGROUND: The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis. CASE SUMMARY: A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as Escherichia fergusonii and Romboutsia timonensis, were more in the patient. Beneficial bacteria such as Faecalibacterium prausnitzii, Fusicatenibacter saccharivorans, Ruminococcus bromii, and Bifidobacterium longum were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as Eubacterium rectale, and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms. CONCLUSION: Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.


Subject(s)
Enteritis , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Radiation Injuries , Uterine Cervical Neoplasms , Humans , Female , Middle Aged , Enteritis/microbiology , Enteritis/diagnosis , Enteritis/etiology , Enteritis/therapy , Radiation Injuries/diagnosis , Radiation Injuries/microbiology , Radiation Injuries/etiology , Radiation Injuries/surgery , Gastrointestinal Microbiome/radiation effects , Fecal Microbiota Transplantation/methods , Uterine Cervical Neoplasms/radiotherapy , RNA, Ribosomal, 16S/genetics , Treatment Outcome , Chronic Disease , Colonoscopy , Intestines/microbiology , Intestines/radiation effects , Feces/microbiology , Radiotherapy/adverse effects
20.
World J Clin Cases ; 12(13): 2194-2200, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38808341

ABSTRACT

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage. Wendan Decoction (WDD) is a traditional Chinese herbal formula used to treat various gastrointestinal disorders, such as gastritis, functional dyspepsia, and irritable bowel syndrome. Mosapride, a prokinetic agent, functions as a selective 5-hydroxytryptamine 4 agonist, enhancing gastrointestinal motility. AIM: To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery. METHODS: Eighty patients with GERD were randomly divided into treatment (receiving WDD combined with mosapride) and control (receiving mosapride alone) groups. The treatment was conducted from January 2021 to January 2023. The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire (RDQ). The secondary outcomes were improved esophageal motility (measured using esophageal manometry), gastric emptying (measured using gastric scintigraphy), and quality of life [measured via the Short Form-36 (SF-36) Health Survey]. RESULTS: The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters, such as lower esophageal sphincter pressure, peristaltic amplitude, and peristaltic velocity compared to the control group. The treatment group showed significantly higher gastric emptying rates and SF-36 scores (in both physical and mental domains) compared to the control group. No serious adverse effects were observed in either group. CONCLUSION: WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery. It can improve GERD symptoms, esophageal motility, gastric emptying, and the quality of life of patients. Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

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