Improved Anti-Oxidant and Anti-Bacterial Capacities of Skim Milk Fermented by Lactobacillus plantarum.

Milk, on account of its abundant protein content, is recognized as a vital source of bioactive substances. In this study, the bioactive ingredients in milk were obtained by a combination of protease hydrolysis and fermentation with Lactobacillus plantarum. The compositions of protease hydrolysate (PM) and fermentation supernatant (FM) were determined, and their anti-oxidant and anti-bacterial activities were evaluated. Using LC-MS/MS, the molecular weights and sequences of the peptides were characterized, among which a total of 25 bioactive peptides were identified. The DPPH radical scavenging results demonstrated that FM exhibited an enhanced anti-oxidant capacity compared to PM. The bacterial survival rate results revealed that FM had a remarkable anti-bacterial ability compared to PM. Additionally, the anti-bacterial component and potential anti-bacterial mechanisms were determined. The results of cytoplasmic membrane depolarization, cell membrane permeability, and morphological observation indicated that FM could interact with bacterial membranes to achieve its anti-bacterial effect. These findings suggested that FM, as a bioactive substance of natural origin, holds potential applications in the functional food, pharmaceutical, and cosmetic industries.

Rapid Differential Detection of Wild-Type Classical Swine Fever Virus and Hog Cholera Lapinized Virus Vaccines by TaqMan MGB-Based Dual One-Step Real-Time RT-PCR.

To establish a rapid real-time RT-PCR method for differentiating wild-type classical swine fever virus (CSFV) strains from vaccine strains (HCLV), we designed a universal primer targeting the NS3 gene to detect wild-type CSFV strains and vaccine strains simultaneously, and two TaqMan-MGB probes were designed to differentiate between wild-type and vaccine strains. After optimizing the RT-qPCR conditions, a rapid dual TaqMan-MGB RT-qPCR method for the detection and identification of CSFV and HCLV was developed. The results showed that method could specifically detect CSFV and HCLV with no cross-reactivity with other swine pathogens. The analytic sensitivity for the NS3 gene of CSFV and HCLV were 1.67 × 101 copies/µL, respectively. For precision testing, the repeatability and reproducibility of the test was less than 2%. This method was successfully used for the rapid detection of 193 biological samples collected from CSFV-vaccinated pigs. This fast and accurate detection technology can be used for the detection of CSFV and is suitable for differentiating between wild-type CSFV strains and vaccine strains.

Facile Preparation of Silica/Tannic Acid/Zein Microcapsules Templated from Non-Aqueous Pickering Emulsions and their Application in Cargo Protection.

Microcapsules have attracted significant attention in academia and industry due to their unique properties for protecting and controlling the release of active substances. However, based on water-insoluble biopolymers, developing a straightforward approach to prepare microcapsules with improved biocompatibility and functional shells remains a great challenge. In this study, zein, a water-insoluble protein, is employed to prepare robust microcapsules facilely using oil-in-aqueous ethanol Pickering emulsions as templates. First, the emulsion template is stabilized by hydrophobic silica nanoparticles with in situ surface modification of tannic acid. The zein is then precipitated at the interface in a controlled manner using antisolvent approach to obtain silica/tannic acid/zein (STZ) microcapsules. It is found that the concentration of zein and the presence of tannic acid played a significant role in the formation of STZ microcapsules with well-defined morphology and a robust shell. The uniform deposition of zein on the surface of template droplets is facilitated by the interactions between tannic acid and zein via hydrogen bond and electrostatic force. Finally, the resulting STZ microcapsules showed super resistance to ultraviolet (UV) radiation and high temperature for the unstable, lipophilic, and active substance of ß-carotene.

Simple and rapid identification of beef within 30 min using a new food nucleic acid release agent combined with direct-fast qPCR.

Simple and rapid molecular detection technologies for authenticating animal species are urgently needed for food safety and authenticity. This study established a new direct-fast quantitative polymerase chain reaction (qPCR) detection technology for beef to achieve rapid and on-site nucleic acid detection in food. This technology can complete nucleic acid extraction in 4 min using a new type of food nucleic acid-releasing agent, followed by direct amplification of the DNA sample by fast qPCR in 25 min. The results indicated that direct-fast qPCR can specifically identify beef and can also identify 0.00001% of beef components in artificially simulated meat mixtures, with a detection precision variation coefficient of <4%. This method can be used to effectively identify beef in different food samples. As a simple, fast, and accurate molecular detection technology for beef, this method may provide a new tool for the on-site detection of beef components in food.

One-Step Formation of Pickering Double Emulsion Costabilized by Hydrophobic Silica Nanoparticles and Sodium Alginate.

Pickering double emulsions exhibit higher stability and biocompatibility compared with surfactant-stabilized double emulsions. However, tailored synthesis of particle stabilizers with appropriate wettability is time consuming and complicated and usually limits their large-scale adoption. Using binary stabilizers may be a simple and scalable strategy for Pickering double emulsion formation. Herein, commercially available hydrophobic silica nanoparticles (SNPs) and sodium alginate (SA) as binary stabilizers are used to prepare O/W/O Pickering double emulsions in one-step emulsification. The influence of system composition on double emulsion preparation is identified by optical microscopy, confocal laser scanning microscopy, and interfacial tension and water contact angle analyses. The formation of the O/W/O Pickering double emulsion depends critically on the aqueous phase viscosity and occurrence of emulsion inversion. Both hydrophobic SNPs and SA adsorb at the droplet surface to provide a steric barrier, while SA also reduces interfacial tension and increases aqueous phase viscosity, giving double emulsion long-term stability. Their microstructure and stability are controlled by adjusting the SA concentration, water-oil volume ratio, concentration and wettability of the particle stabilizer, and oil type. As a demonstration, the middle layer of the as-prepared O/W/O Pickering double emulsions can be cross-linked in situ with calcium ions to produce calcium alginate porous microspheres. We believe that our strategy for double emulsion formation holds great potential for practical applications in food, cosmetics, or pharmaceuticals.

Morpholine-modified Ru-based agents with multiple antibacterial mechanisms as metalloantibiotic candidates against Staphylococcus aureus infection.

Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently needed to develop new antibacterial drugs with unique mechanisms of action. As a versatile moiety, morpholine has been widely employed to enhance the potency of numerous bioactive molecules. In this study, a series of ruthenium-based antibacterial agents modified with the morpholine moiety were designed and characterized, aiming to obtain a promising metalloantibiotic with a multitarget mechanism. Antibacterial activity screening demonstrated that the most active complex Ru(ii)-3 exhibited the strongest potency against Staphylococcus aureus (S. aureus) with an MIC value of only 0.78 µg mL-1, which is better than most clinically used antibiotics. Notably, Ru(ii)-3 not only possessed excellent bactericidal efficacy, but could also overcome bacterial resistance. Importantly, Ru(ii)-3 very efficiently removed biofilms produced by bacteria, inhibited the secretion of bacterial exotoxins, and enhanced the activity of many existing antibiotics. The results of mechanism studies confirmed that Ru(ii)-3 could destroy the bacterial membrane and induce ROS production in bacteria. Furthermore, animal infection models confirmed that Ru(ii)-3 showed significant anti-infective activity in vivo. Overall, this work demonstrated that a morpholine-modified ruthenium-based agent is a promising antibiotic candidate in tackling the crisis of drug-resistant bacteria.

Preparation and Application of High Internal Phase Pickering Emulsion Gels Stabilized by Starch Nanocrystal/Tannic Acid Complex Particles.

Herein, the starch nanocrystal/tannic acid (ST) complex particles, which were prepared based on the hydrogen bond between starch nanocrystal (SNC) and tannic acid (TA), were successfully used to stabilize the HIPPE gels. The optimal TA concentration of the ST complex particles resulted in better water dispersibility, surface wettability, and interfacial activity as compared to SNC. The hydrogen bond responsible for the formation of ST complex particles and subsequent stable emulsions was demonstrated by varying the pH and ionic strength of the aqueous phase. Notably, the HIPPE gels stabilized via the ST complex particles can maintain long-term stability for up to three months. The HIPPEs stabilized via the ST complex particles all displayed gel-like features and had smaller droplets and denser droplet networks than the SNC-stabilized HIPPEs. The rheological behavior of HIPPE gels stabilized via the ST complex particles can be readily changed by tuning the mass ratio of SNC and TA as well as pH. Finally, the prepared HIPPE gels used to effectively protect encapsulated ß-carotene against high temperatures and ultraviolet radiation and its controllable release at room temperature were demonstrated. It is anticipated that the aforementioned findings will provide new perspectives on the preparation of Pickering emulsion for delivery systems.

Evaluation of multi-target iridium(iii)-based metallodrugs in combating antimicrobial resistance and infections caused by Staphylococcus aureus.

The rapid emergence and spread of multidrug-resistant bacteria pose a serious challenge to human life and health, necessitating the development of novel antibacterial agents. Herein, to address this challenge, three iridium-based antibacterial agents were prepared and their antimicrobial activity were explored. Importantly, the three complexes all showed robust potency against S. aureus with MIC values in the range of 1.9-7.9 µg mL-1. Notably, the most active complex Ir3 also exhibited relative stability in mammalian fluids and a significant antibacterial effect on clinically isolated drug-resistant bacteria. Mechanism studies further demonstrated that the complex Ir3 can kill S. aureus by disrupting the integrity of the bacterial membrane and inducing ROS production. This multi-target advantage allows Ir3 to not only effectively combat bacterial resistance but also efficiently clear the bacterial biofilm. In addition, when used together, complex Ir3 could enhance the antibacterial potency of some clinical antibiotics against S. aureus. Moreover, both G. mellonella wax worms and mouse infection model demonstrated that Ir3 has low toxicity and robust anti-infective efficacy in vivo. Overall, complex Ir3 can serve as a new antibacterial agent for combating Gram-positive bacterial infections.

Compound Microalgae-Type Biofunctional Hydrogel for Wound Repair during Full-Thickness Skin Injuries.

A dual biofunctional hydrogel (HQCS-SP) wound dressing, offering antibacterial properties and a biological response, was innovatively designed and developed to repair full-layer skin defects. The HQCS-SP hydrogel creates an artificial matrix that facilitates cell recruitment, extracellular matrix deposition, exhibiting exceptional tissue affinity, robust self-healing, effective hemostatic capabilities and accelerates wound healing. It is synthesized by crosslinking modified chitosan (HQCS) with spirulina protein (SP) and Fe3+. The HQCS provides antibacterial, antioxidant, good tissue affinity and excellent hemostasis performance. The incorporation of SP not only reinforces the antioxidant, antibacterial, anti-inflammatory, and pro-angiogenesis effects but also participates in the regulation of signal pathways and promotes wound healing. Therefore, this study offers a new visual angle for the design of advanced functional trauma dressings with great application potential in the bio-medical field.

Static charge is an ionic molecular fragment.

What is static charge? Despite the long history of research, the identity of static charge and mechanism by which static is generated by contact electrification are still unknown. Investigations are challenging due to the complexity of surfaces. This study involves the molecular-scale analysis of contact electrification using highly well-defined surfaces functionalized with a self-assembled monolayer of alkylsilanes. Analyses show the elementary molecular steps of contact electrification: the exact location of heterolytic cleavage of covalent bonds (i.e., Si-C bond), exact charged species generated (i.e., alkyl carbocation), and transfer of molecular fragments. The strong correlation between charge generation and molecular fragments due to their signature odd-even effects further shows that contact electrification is based on cleavage of covalent bonds and transfer of ionic molecular fragments. Static charge is thus an alkyl carbocation; in general, it is an ionic molecular fragment. This mechanism based on cleavage of covalent bonds is applicable to general types of insulating materials, such as covalently bonded polymers. The odd-even effect of charging caused by the difference of only one atom explains the highly sensitive nature of contact electrification.

Dysregulation of Serum UCA1 and Its Clinical Significance in Patients with Acute Cerebral Infarction.

OBJECTIVE: To investigate the expression of lncRNA UCA1 in serum of patients with acute cerebral infarction (ACI) and its relationship with prognosis. METHODS: The serum lncRNA UCA1 level in participants was detected, and the correlation between the neurological function score (NIHSS score) of ACI patients and lncRNA UCA1 expression was analyzed. Patients were followed up at 3 months after discharge and were divided into favorable and unfavorable prognostic groups according to the modified Rankin scale (mRs). The risk factors of ACI patients with poor prognosis were analyzed, and the predictive value of each index for ACI prognosis was evaluated by ROC curve. RESULTS: The level of lncRNA UCA1 in ACI group was increased (P<0.001). ROC analysis showed that high lncRNA UCA1 expression had clinical significance for the diagnosis of ACI. Spearman correlation analysis revealed that NIHSS score was positively correlated with lncRNA UCA1 expression level in ACI group (r=0.6537, P<0.001). Hcy level and NIHSS score in poor prognosis group (n=63) were higher than those in good prognosis group (n=84), and lncRNA UCA1 level in serum in poor prognosis group was increased in comparison to good prognosis group (P<0.05). Logistic regression analysis investigated that admission NIHSS score, infarct size, and increased lncRNA UCA1 were the risk factors affecting the prognosis of ACI. CONCLUSION: Serum lncRNA UCA1 is abnormally elevated in ACI patients, and the elevated lncRNA UCA1 not only shows high accuracy in the diagnosis of ACI, but also has a certain predictive value for poor prognosis of ACI.

Establishment and Validation of the LI-RADS Morphologic Type II Hepatocellular Carcinoma Early Recurrence Risk Scoring System.

BACKGROUND: Tumor morphology links to early recurrence of hepatocellular carcinoma. Controversy exists regarding the recurrence risk of Liver Imaging Reporting and Data System morphologic Type II hepatocellular carcinoma. This study aims to explore risk factors for early recurrence of Type II hepatocellular carcinoma. METHODS: Retrospective analysis of hepatocellular carcinoma patients who underwent curative resection and preoperative contrast-enhanced MRI from June 2016 to June 2020. Our patients formed the development set, and hepatocellular carcinoma patients from the TCIA database served as validation. Univariable and multivariable Cox regression identified independent risk factors for early recurrence. A risk scoring system was established for risk stratification, and an early recurrence prediction model was developed and validated. RESULTS: 95 Type II hepatocellular carcinoma patients were in the development set, and 29 cases were in the validation set. Early recurrence rates were 33.7% and 37.9%, respectively. Multivariate analysis revealed age, histological grade, AFP, and intratumoral hemorrhage as independent risk factors for early recurrence. The model's diagnostic performance for early recurrence was AUC = 0.817 in the development set. A scoring system classified patients into low-risk (scores ≤ 3) and high-risk (scores > 3) groups. The high-risk group had significantly lower recurrence-free survival (40.0% vs 73.2%, P = 0.001), consistent with the validation set (25.0% vs 73.3%, P = 0.028). CONCLUSIONS: The risk scoring system demonstrated excellent discrimination and predictive ability, aiding clinicians in assessing early recurrence risk and identifying high-risk individuals effectively.

Cognitive status and its risk factors in patients with hypertension and diabetes in a low-income rural area of China: A cross-sectional study.

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.

Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics.

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB. Methods: The mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein-protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA. Results: A total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD. Conclusion: The seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

Identification of cuproptosis-related lncRNAs for prognosis and immunotherapy in glioma.

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.

CD20-positive subcutaneous panniculitis-like T-cell lymphoma presenting as polycranial neuropathy: A CARE-compliant case report and literature review.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma(SPTCL) is a very rare cytotoxic T-cell skin lymphoma involving subcutaneous tissue, and mainly affects young females. T-cell phenotype is characterized by CD3+, CD8+, and CD4-. SPTCT with polycranial neuropathy has rarely been described. SPTCL is believed to show an indolent clinical course unless patients develop haemophagocytic syndrome or sudden respiratory failure. Its treatment has not been established yet. CASE PRESENTATION: We report a case of intractable SPTCT in a 66-year-old woman with multiple cranial nerve palsies and diabetes. She showed involvement of the bilateral facial nerve, left trigeminal nerve, left auditory nerve, and right oculomotor nerve. The single inconspicuous skin lesion in the trunk presented with an erythematous nodule with a diameter of <5 cm and a slightly pink infiltrated plaque. Electromyography revealed bilateral damage to the facial nerve. Differential immunohistochemical characteristics were observed. Immunohistochemistry demonstrated diffuse CD20 positivity. Cerebral spinal fluid analysis revealed elevated protein levels of 0.92 (0.15-0.45) g/L. Her condition regressed severely over time. She was treated with chemotherapy but died 10 months later, the probable cause of death was lung involvement. CONCLUSION: The patient's involvement with the central nervous system may be associated with positivity for CD20. Molecular biomarkers may act as therapeutic targets for SPTCL.

Derivation and validation of a 18F-FDG PET/CT scoring model to predict malignant pleural effusion.

OBJECTIVE: To develop an 18F-fluorodeoxyglucose PET/computed tomography (CT) scoring model based on metabolic and radiologic findings of the pleura and fluid to identify malignant pleural effusion. METHODS: The PET and CT findings from patients with pleural effusion in the derivation dataset were used to develop a scoring model. Then, the diagnostic accuracy of the predictive score was verified by the validation dataset. RESULTS: Eight parameters independently predicting malignancy were retained in the scoring model, including pleural nodules or masses (4 points), focal pleural thickening (2 points), absence of pleural loculation (2 points), thickness of mediastinal pleura involvement ≥0.5 cm (2 points), maximum standardized uptake value (SUVmax) of mediastinal pleura involvement ≥2.3 (2 points), thickness of nonmediastinal pleura involvement ≥0.5 cm (1 point), SUVmax of nonmediastinal pleura involvement ≥3.0 (1 point) and fluid SUVmax ≥1.6 (1 point). The operating characteristics of the PET/CT score were 0.958 area under the curve (AUC), 88.6% sensitivity, 91.2% specificity, 10.09 positive likelihood ratio and 0.13 negative likelihood ratio, with 6 points as the threshold. These values in the validation dataset were 0.947, 91.7%, 88.4%, 7.91 and 0.094, respectively. No difference was found in AUCs between the derivation and validation datasets (z = 0.517, P = 0.697). The negative predictive value was 99.4% in the score from 0 to 2, and the positive predictive value was 98.3% for patients with score between 9 and 15. CONCLUSIONS: The PET/CT scoring model is a valuable strategy to help physicians to distinguish malignant-benign pleural effusion and stratify patients who will benefit from invasive procedures.

Response Evaluation and Survival Prediction Following PD-1 Inhibitor in Patients With Advanced Hepatocellular Carcinoma: Comparison of the RECIST 1.1, iRECIST, and mRECIST Criteria.

BACKGROUND: Precise evaluation of the efficacy of immunotherapy is critical in the effective management and treatment of advanced hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to compare the response assessments achieved by different criteria and to evaluate the correlation between survival outcome and response assessment in HCC treated with programmed cell death protein 1 (PD-1) inhibitor. METHODS: Fifty patients with advanced HCC treated with first-line PD-1 inhibitor with baseline and follow-up CT images were analyzed. The patients were categorized into responders and nonresponders according to the criteria. RESULTS: When the response assessments between RECIST 1.1 and mRECIST were compared, no statistically significant differences were observed. Overall response rate was 16% by RECIST 1.1 and iRECIST and was 24% by mRECIST. According to RECIST 1.1 and mRECIST, overall survival (OS) and progression-free survival (PFS) were not statistically different between the complete response (CR) and partial response (PR) groups and the stable disease (SD) and progressive disease (PD) groups. The OS and PFS were significantly different between responders and nonresponders according to mRECIST. The Cohen's Kappa for RECIST 1.1, iRECIST, and mRECIST was 0.534, 0.438, and 0.363, respectively. CONCLUSION: The mRECIST criteria have a powerful ability to discriminate between responders and nonresponders and demonstrated significantly longer OS and PFS in responders than in nonresponders. However, mRECIST needs to be further improved in order for it to be widely used in the clinical evaluation of immunotherapy in HCC.

miRNA-223-3p modulates ibrutinib resistance through regulation of the CHUK/Nf-κb signaling pathway in mantle cell lymphoma.

Since the use of Bruton's tyrosine kinase (BTK) inhibitor ibrutinib in relapsed/refractory (R/R) mantle cell lymphoma (MCL), the problem of drug resistance has become increasingly prominent. Though it has been proven that the nonclassic nuclear factor κB pathway (nonclassic NF-κB pathway) correlates with ibrutinib resistance in MCL, the upstream regulator is unknown. In the present study, conserved helix-loop-helix ubiquitous kinase (CHUK) overexpression accelerated proliferation and suppressed apoptosis of MCL cells after ibrutinib treatment in vitro. The results of luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot revealed that CHUK was targeted and negatively regulated by miRNA-223-3p. miRNA-223-3p knockdown promoted proliferation and inhibited apoptosis of MCL cells after ibrutinib treatment in vitro and vivo, whereas CHUK knockdown reversed downregulated miRNA-223-3p-promoted cell proliferation after ibrutinib treatment in vitro. In conclusion, miRNA-223-3p modulates ibrutinib resistance through regulation of the CHUK/NF-κB signaling pathway in MCL, which is crucial in providing a marker to predict disease response.

LncRNA LUADT1 is Upregulated in Mantle Cell Lymphoma and Modulates TRIM11 by Sponging miR-24-3p to Inhibit Cell Apoptosis.

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.