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1.
PLoS Pathog ; 20(5): e1012187, 2024 May.
Article En | MEDLINE | ID: mdl-38718038

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.


Carbapenems , Klebsiella pneumoniae , beta-Lactamases , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/metabolism , Klebsiella pneumoniae/drug effects , beta-Lactamases/genetics , beta-Lactamases/metabolism , Carbapenems/pharmacology , Humans , Gene Expression Regulation, Bacterial , Anti-Bacterial Agents/pharmacology , Klebsiella Infections/microbiology , Klebsiella Infections/drug therapy , Klebsiella Infections/genetics , Carbapenem-Resistant Enterobacteriaceae/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , RNA, Small Untranslated/genetics , RNA, Bacterial/genetics , Microbial Sensitivity Tests
2.
J Proteome Res ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38723043

Acupuncture is widely used to treat dry eye disease (DED), but its effect has not been reported in treating video display terminal (VDT)-related dry eye, and the mechanism of acupuncture on VDT-related dry eye is also unknown. In our study, the tear proteome was compared with identifying possible mechanisms and biomarkers for predicting acupuncture effectiveness in VDT-related dry eye. The results showed that the ocular surface disease index scores were significantly different between the acupuncture group (AC group) and artificial tears group (AT group) at the end of the study, whereas tear film breakup time (TFBUT) and Schirmer I test (SIT) were not significantly different between the groups. Proteome changes pre- and post-treatment in the AC group were associated with B cell-related immune processes, inflammation, glycolysis, and actin cytoskeleton. Furthermore, the proteins hexosaminidase A and mannose-binding lectin 1 could prospectively predict whether acupuncture treatment was effective. Therefore, we believe that acupuncture can provide greater improvement in the clinical symptoms of VDT-related dry eye than artificial tears. The mechanism of acupuncture in VDT-related dry eye treatment may be associated with glycolysis- and actin cytoskeleton remodeling-mediated inflammatory and immune processes. Additionally, hexosaminidase A and mannose-binding lectin 1 are biomarkers for predicting the efficacy of acupuncture for VDT-related dry eye.

3.
Article En | MEDLINE | ID: mdl-38723155

Lead and its compounds can have cumulative harmful effects on the nervous, cardiovascular, and other systems, and especially affect the brain development of children. We collected 4918 samples from 15 food categories in 11 districts of Guangzhou, China, from 2017 to 2022, to investigate the extent of lead contamination in commercial foods and assess the health risk from dietary lead intake of the residents. Lead was measured in the samples using inductively coupled plasma mass spectrometry. Dietary exposure to lead was calculated based on the food consumption survey of Guangzhou residents in 2011, and the health risk of the population was evaluated using the margin of exposure (MOE) method. Lead was detected in 76.5% of the overall samples, with an average lead content of 29.4 µg kg-1. The highest lead level was found in bivalves. The mean daily dietary lead intakes were as follows: 0.44, 0.34, 0.25, and 0.28 µg kg-1 body weight (bw) day-1 for groups aged 3-6, 7-17, 18-59, and ≥ 60 years, respectively. Rice and rice products, leafy vegetables, and wheat flour and wheat products were identified as the primary sources of dietary lead exposure, accounting for 73.1%. The MOE values demonstrated the following tendency: younger age groups had lower MOEs, and 95% confidence ranges for the groups aged 3-6 and 7-17 began at 0.6 and 0.7, respectively, indicating the potential health risk of children, while those for other age groups were all above 1.0. Continued efforts are needed to reduce dietary lead exposure in Guangzhou.

4.
Microbes Infect ; : 105350, 2024 May 07.
Article En | MEDLINE | ID: mdl-38723999

The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 =98.7%, p=0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.

5.
Article En | MEDLINE | ID: mdl-38743293

Recombinant human erythropoietin (rhEPO) is a glycoprotein that acts as the main hormone involved in regulating red blood cell production to treat anemia caused by chronic kidney disease or chemotherapy, which has three N-glycosylation sites and one O-glycosylation site. It contains a variety of different glycosylation modifications, such as sialyation, O-acetylation on sialic acids, etc., which causes a big challenge for the glycosylation analysis of rhEPO. In this study, a liquid chromatography-mass spectrometry (LC-MS) method combined with electron-activated dissociation (EAD) technology was used in qualitative and quantitative characterization of rhEPO N-glycosylation and O-glycosylation in just one injection. The usage of EAD not only generated abundant MS/MS fragment ions of glycopeptides and improved the MS/MS sequence coverage but also preserved the glycan structures in the MS/MS fragment ions and the integrity of the glycosidic bond between the glycans and peptides. Three N-glycosylation sites (N24, N38, and N83) and one O-glycosylation site (S126) of rhEPO samples were successfully identified. Among them, the glycosylation ratios of N24, N38, and N83 sites were 82.7%, 100%, and 100% respectively, and 15, 10, and 12 different N-glycans could be identified at the glycopeptide level. The total average number of sialic acids, N-hydroxyacetylneuraminoic acid, and O-acetylation on sialic acid were 7.28, 4.21, and 0.66 at the intact protein level, respectively. For O-glycosylation site S126, O-glycosylation ratios analyzed at the intact protein level and the glycopeptide level were 80.2% and 80.3%, respectively, and two O-glycans were identified, including Core1_S1 and Core1_S2. This study also compared the difference of the glycans and their relative contents in batch-to-batch rhEPO samples. The results proved that the workflow using EAD fragmentation in LC-MS method could be effectively applied for characterizing the glycosylation analysis of rhEPO samples and batch-to-batch consistency analysis, which would help to reasonably guide the optimization of rhEPO production process.

6.
Article En | MEDLINE | ID: mdl-38743900

Objective: This study aims to evaluate the effects of hydrogen therapy on nerve function and tumor progression markers in glioma patients, focusing on the modulation of oxidative stress and cadherin expression to establish its potential as a complementary treatment. Methods: 100 glioma patients were enrolled and divided into two groups using the random number table: routine treatment (50) and hydrogen inhalation plus routine treatment (50). After 2 weeks of treatment, clinical curative effect, levels of nerve function indexes [national institute of health stroke scale (NIHSS), central nervous specific protein (S100ß), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP)], oxidative stress indexes [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)] and E-cadherin before and after treatment, and occurrence of adverse reactions during treatment were compared between the two groups. Results: After treatment, the overall effect of the hydrogen inhalation group (90.00%) was significantly better than that of the conventional group (72.00%), which was statistically significant (P = .022). In terms of specific biomarkers, post-treatment levels of E-cadherin were elevated to 0.84±0.05 ng/mL in the hydrogen group compared to 0.72±0.06 ng/mL in the routine group. SOD and CAT levels rose to 63.21±5.36 U/L and 8.01±0.54 U/mL, respectively, versus 52.31±5.24 U/L and 5.25±0.59 U/mL in the routine group (P < .05 for both). Conversely, the NIHSS scores decreased significantly to 12.19±2.08 in the hydrogen group, compared to 16.92±2.23 in the routine group. Similarly, S100ß, NSE, GFAP, and MDA levels were found to be lower in the hydrogen group (0.41±0.09 µg/L, 8.24±1.64 ng/mL, 0.71±0.23 pg/mL, and 6.05±1.08 mmol/L respectively) than in the routine group (0.66±0.12 µg/L, 10.67±1.83 ng/mL, 0.93±0.29 pg/mL, and 7.21±1.12 mmol/L respectively) with P < .05 for all comparisons. The total incidence of adverse reactions was slightly lower in the hydrogen group (64.00%) compared to the routine group (68.00%), but this difference was not statistically significant (χ2=0.178, P = .673). Conclusion: Hydrogen inhalation therapy significantly enhances nerve function, reduces local oxidative stress levels, and increases E-cadherin levels in patients with brain glioma, suggesting its potential as an adjunct treatment. The findings underscore the therapy's role in enhancing patient recovery and guiding future research and treatment strategies.

7.
Talanta ; 276: 126250, 2024 May 11.
Article En | MEDLINE | ID: mdl-38743969

In this research, self-screening aptamer and MOFs-derived nanomaterial have been combined to construct electrochemical aptasensor for environmental detection. By utilizing the large specific surface area of reduced graphene oxide (rGO), ZIF-8 was grown in situ on surface of rGO, and the composites was pyrolyzed to obtain MOFs-derived porous carbon materials (rGO-NCZIF). Thanks to the synergistic effect between rGO and NCZIF, the complex exhibits remarkable characteristics, including a high electron transfer rate and electrocatalytic activity. In addition, the orderly arrangement of imidazole ligands within ZIF-8 facilitated the uniform doping of nitrogen elements into the porous carbon, thereby significantly enhancing its electrochemical performance. After carboxylation, rGO-NCZIF was functionalized with self-screening aptamer for fabricating electrochemical aptasensor, which can be used to detect Erwinia cypripedii, a kind of quarantine plant bacteria, with detection limit of 4.92 × 103 cfu/mL. Due to the simplicity and speed, the aptasensor is suitable for rapid customs inspection and quarantine. Additionally, the universality of this sensing strategy was verified through exosomes detection by changing the aptamer. The results indicated that the rGO-NCZIF-based electrochemical aptasensor had practical value in the environmental and medical fields.

8.
Nat Biotechnol ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38744947

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

9.
J Antibiot (Tokyo) ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38745102

Four new echinomycin congeners, quinomycins M-P (1-4) were isolated from the cultures of the soil-derived Streptomyces sp. CPCC205575. The planar structures were determined by comprehensive analyses of NMR and HRESIMS/MS data. The absolute configurations were elucidated by the advanced Marfey's method combined with biosynthetic gene analysis. Compounds 1-4 represent the first examples of quinomycin-type natural products with the sulfur atom at the N,S-dimethylcysteine residue oxidized as a sulfoxide group forming the unusual N-methyl-3-methylsulfinyl-alanine residue. Bioassay results revealed that the oxidation of the sulfur atom at the Cys or Cys' residues led to dramatic decrease of cytotoxicity and antimicrobial activity.

11.
Immunol Res ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38748318

Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a severe complication of sepsis characterized by acute respiratory distress, hypoxemia, and diffuse bilateral pulmonary infiltrates. The regulation of RIPK1 is an important part of the inflammatory response, and cIAP1/2 serves as the E3 ubiquitin ligase for RIPK1. In this study, we investigated the effect and mechanism of cIAP1/2 inhibition on sepsis-induced lung injury. Our results showed that cIAP1/2 inhibition can alleviate sepsis-induced lung injury and reduce the inflammatory response, which is accompanied by downregulation of RIPK1 phosphorylation and ubiquitination. Additionally, cIAP1/2 inhibition led to the up-regulation of programmed cell death, including apoptosis, necroptosis, and pyroptosis, and inhibiting these three cell death pathways can further reduce the inflammatory response, which is similar to the recently discovered programmed cell death pathway PANoptosis. Our findings suggest that cIAP1/2 and PANoptosis inhibition may be a new strategy for treating sepsis-induced lung injury and provide important references for further exploring the mechanism of sepsis-induced lung injury and identifying new therapeutic targets.

12.
Molecules ; 29(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38731479

Manganese molybdate has garnered considerable interest in supercapacitor research owing to its outstanding electrochemical properties and nanostructural stability but still suffers from the common problems of transition metal oxides not being able to reach the theoretical specific capacitance and lower electrical conductivity. Doping phosphorus elements is an effective approach to further enhance the electrochemical characteristics of transition metal oxides. In this study, MnMoO4·H2O nanosheets were synthesized on nickel foam via a hydrothermal route, and the MnMoO4·H2O nanosheet structure was successfully doped with a phosphorus element using a gas-solid reaction method. Phosphorus element doping forms phosphorus-metal bonds and oxygen vacancies, thereby increasing the charge storage and conductivity of the electrode material. The specific capacitance value is as high as 2.112 F cm-2 (1760 F g-1) at 1 mA cm-2, which is 3.2 times higher than that of the MnMoO4·H2O electrode (0.657 F cm-2). The P-MnMoO4//AC ASC device provides a high energy density of 41.9 Wh kg-1 at 666.8 W kg-1, with an 84.5% capacity retention after 10,000 charge/discharge cycles. The outstanding performance suggests that P-MnMoO4 holds promise as an electrode material for supercapacitors.

13.
Plants (Basel) ; 13(9)2024 May 06.
Article En | MEDLINE | ID: mdl-38732492

Tomato yellow leaf curl virus (TYLCV) is a prominent viral pathogen that adversely affects tomato plants. Effective strategies for mitigating the impact of TYLCV include isolating tomato plants from the whitefly, which is the vector of the virus, and utilizing transgenic lines that are resistant to the virus. In our preliminary investigations, we observed that the use of growth retardants increased the rate of TYLCV infection and intensified the damage to the tomato plants, suggesting a potential involvement of gibberellic acid (GA) in the conferring of resistance to TYLCV. In this study, we employed an infectious clone of TYLCV to inoculate tomato plants, which resulted in leaf curling and growth inhibition. Remarkably, this inoculation also led to the accumulation of GA3 and several other phytohormones. Subsequent treatment with GA3 effectively alleviated the TYLCV-induced leaf curling and growth inhibition, reduced TYLCV abundance in the leaves, enhanced the activity of antioxidant enzymes, and lowered the reactive oxygen species (ROS) levels in the leaves. Conversely, the treatment with PP333 exacerbated TYLCV-induced leaf curling and growth suppression, increased TYLCV abundance, decreased antioxidant enzyme activity, and elevated ROS levels in the leaves. The analysis of the gene expression profiles revealed that GA3 up-regulated the genes associated with disease resistance, such as WRKYs, NACs, MYBs, Cyt P450s, and ERFs, while it down-regulated the DELLA protein, a key agent in GA signaling. In contrast, PP333 induced gene expression changes that were the opposite of those caused by the GA3 treatment. These findings suggest that GA plays an essential role in the tomato's defense response against TYLCV and acts as a positive regulator of ROS scavenging and the expression of resistance-related genes.

14.
China CDC Wkly ; 6(16): 350-356, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38736468

Introduction: The current study aims to assess the performance of data mining techniques in detecting safety signals for adverse events following immunization (AEFI) using routinely obtained data in China. Four different methods for detecting vaccine safety signals were evaluated. Methods: The AEFI data from 2011 to 2015 was collected for our study. We analyzed the data using four different methods to detect signals: the proportional reporting ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). Each method was evaluated at 1-3 thresholds for positivity. To assess the performance of these methods, we used the published signal rates as gold standards to determine the sensitivity and specificity. Results: The number of identified signals varied from 602 for PRR1 (with a threshold of 1) to 127 for MGPS1. When considering the common reactions as the reference standard, the sensitivity ranged from 0.9% for MGPS1/2 to 38.2% for PRR1/2, and the specificity ranged from 85.2% for PRR1 and ROR1 to 96.7% for MGPS1. When considering the rare reactions as the reference standard, PRR1, PRR2, ROR1, ROR2, and BCPNN exhibited the highest sensitivity (73.3%), while MGPS1 exhibited the highest specificity (96.9%). Discussion: For common reactions, the sensitivities were modest and the specificities were high. For rare reactions, both the sensitivities and specificities were high. Our study provides valuable insights into the selection of signal detection methods and thresholds for AEFI data in China.

15.
Cytotechnology ; 76(3): 291-300, 2024 Jun.
Article En | MEDLINE | ID: mdl-38736725

Pulmonary fibrosis (PF) is a chronic lung disease that has a poor prognosis and a serious impact on the quality of life of patients. Here, we investigated the potential role of miR-92a-3p in PF. The mRNA level of miR-92a-3p was significantly increased in both the lung tissues of bleomycin (BLM)--treated mice and pulmonary microvascular endothelial cells (PMVECs). Overexpressing miR-92a-3p increased the mRNA and protein levels of α­SMA, vimentin, and Col-1 but downregulated E-cadherin. Additionally, the protein and mRNA expression levels of KLF2 were significantly decreased in the lung tissues of BLM-treated mice, suggesting that KLF2 participated in the progression of BLM-induced PF. Downregulating miR-92a-3p upregulated the expression of KLF2 and inhibited the endothelial-to-mesenchymal transition (EndoMT) process, thus alleviating PF in vivo. Altogether, a miR-92a-3p deficiency could significantly reduce the development of myofibroblasts and ameliorate PF progression.

16.
ACS Omega ; 9(18): 20119-20128, 2024 May 07.
Article En | MEDLINE | ID: mdl-38737085

A new biochar (N-BC) was fabricated by incorporating high-density positively charged quaternary ammonium groups into the pristine biochar without any adsorption for phosphate. N-BC can highly efficiently remove phosphate with an optimal pH of 5.0, a maximum experimental adsorption capacity of 30 mg of P/g, and an adsorption equilibrium time of 180 min. The predicted pore diffusion coefficient D (the diffused surface area of the adsorbate for unit time) for phosphate adsorption by N-BC was 5.3 × 10-9 cm2/s. N-BC can still capture phosphate in the copresence of anion Cl- with a molar concentration 50 times that of phosphate. The exhausted N-BC was completely regenerated using a 10 wt % NaOH solution and further reused without any observable loss in adsorption capacity. Moreover, N-BC yielded ∼324 bed volumes (BV) of wastewater containing 1 mg P/L phosphate and 50 mg/L Cl- before breakthrough occurring (<0.1 mg P/L in effluent) in a fixed-bed column operation system. The introduced quaternary ammonium groups covalently bound to biochar played a dominant role in phosphate sequestration by N-BC through forming the out-sphere complexation with phosphate. All results imply that it is of promising prospect for N-BC practical application for phosphate purification from waters. The present study provided a new strategy to expand the application of biochar, usually serving as an adsorbent for cationic pollutants, to the purification of anionic pollutants such as phosphate from waters.

17.
Front Neurosci ; 18: 1394169, 2024.
Article En | MEDLINE | ID: mdl-38737098

Objective: This study aims to compare gray matter volume changes in patients with chronic kidney disease (CKD) undergoing peritoneal dialysis (PD) and hemodialysis (HD) using voxel-based morphometry (VBM). Methods: A total of 27 PD patients, 25 HD patients, and 42 healthy controls were included. VBM analysis was performed, and cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment Scale (MoCA). The correlation between cognitive function and changes in brain gray matter volume was analyzed. Results: Both peritoneal dialysis and hemodialysis patients had partial gray matter volume reduction compared to the controls, but the affected brain regions were not uniform. The hemodialysis patients had greater volume reduction in certain brain regions than the PD patients. The MMSE and MoCA scores were positively correlated with gray matter volume changes. Conclusion: Different dialysis modalities cause damage to specific areas of the brain, which can be detected using VBM. VBM, combined with cognitive function assessment, can help detect structural brain changes and cognitive impairment in patients with different dialysis modalities. The comprehensive application of VBM in the field of neurological function deserves further exploration.

18.
Angew Chem Int Ed Engl ; : e202407898, 2024 May 13.
Article En | MEDLINE | ID: mdl-38739536

The quest for smart electronics with higher energy densities has intensified the development of high-voltage LiCoO2 (LCO). Despite their potential, LCO materials operating at 4.7 V faces critical challenges, including interface degradation and structural collapse. Herein, we propose a collective surface architecture through precise nanofilm coating and doping that combines an ultra-thin LiAlO2 coating layer and gradient doping of Al. This architecture not only mitigates side reactions, but also improves the Li+ migration kinetics on the LCO surface. Meanwhile, gradient doping of Al inhibited the severe lattice distortion caused by the irreversible phase transition of O3-H1-3-O1, thereby enhanced the electrochemical stability of LCO during 4.7 V cycling. DFT calculations further revealed that our approach significantly boosts the electronic conductivity. As a result, the modified LCO exhibited an outstanding reversible capacity of 230 mAh g-1 at 4.7 V, which is approximately 28% higher than the conventional capacity at 4.5 V. To demonstrate their practical application, our cathode structure shows improved stability in full pouch cell configuration under high operating voltage. LCO exhibited an excellent cycling stability, retaining 82.33% after 1000 cycles at 4.5 V. This multifunctional surface modification strategy offers a viable pathway for the practical application of LCO materials.

19.
Nat Commun ; 15(1): 3860, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719824

Dual blocker therapy (DBT) has the enhanced antitumor benefits than the monotherapy. Yet, few effective biomarkers are developed to monitor the therapy response. Herein, we investigate the DBT longitudinal plasma proteome profiling including 113 longitudinal samples from 22 patients who received anti-PD1 and anti-CTLA4 DBT therapy. The results show the immune response and cholesterol metabolism are upregulated after the first DBT cycle. Notably, the cholesterol metabolism is activated in the disease non-progressive group (DNP) during the therapy. Correspondingly, the clinical indicator prealbumin (PA), free triiodothyronine (FT3) and triiodothyronine (T3) show significantly positive association with the cholesterol metabolism. Furthermore, by integrating proteome and radiology approach, we observe the high-density lipoprotein partial remodeling are activated in DNP group and identify a candidate biomarker APOC3 that can reflect DBT response. Above, we establish a machine learning model to predict the DBT response and the model performance is validated by an independent cohort with balanced accuracy is 0.96. Thus, the plasma proteome profiling strategy evaluates the alteration of cholesterol metabolism and identifies a panel of biomarkers in DBT.


Cholesterol , Proteome , Humans , Cholesterol/blood , Cholesterol/metabolism , Proteome/metabolism , Female , Male , Middle Aged , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/metabolism , CTLA-4 Antigen/blood , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/blood , Biomarkers/blood , Aged , Triiodothyronine/blood , Machine Learning , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Neoplasms/drug therapy , Neoplasms/blood , Neoplasms/metabolism , Proteomics/methods
20.
Ann Gen Psychiatry ; 23(1): 16, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720347

BACKGROUND: Adolescents with depression who engage in non-suicidal self harming behaviors are more likely to adopt negative coping strategies when faced with negative events. Therefore, these patients should be introduced to positive coping strategies. Evidences have showed that mindfulness-based interventions can positively impact the psychology of patients with mental disorders. This study was to explore the impact of a combination of mindfulness therapy and mentalization-based family therapy (MBFT) on suicidal ideation in adolescents with depressive disorder. METHODS: Eighty adolescent patients with depression and suicidal ideation admitted to our hospital from September 2021 to February 2022 were selected as subjects. They were divided into a control group and a study group using the random number table method, with each group comprising 40 subjects. The control group received MBFT, whereas the study group received both mindfulness therapy and MBFT. The psychological status and suicidal ideations of the two groups were compared before and after the intervention. RESULTS: The psychological health scores of both groups of patients were lower after the intervention, with the scores of the study group being lower than those of the control group (P < 0.05). The scores on the suicidal ideation scales for both groups were lower after intervention, and the study group scored lower than the control group (P < 0.05). The absolute values of the differences in psychological health scale scores and suicidal ideation scale scores before and after the intervention were higher in the study group than in the control group (P < 0.05). CONCLUSION: The combination of mindfulness therapy and MBFT can improve the psychological condition of adolescents with depression, reduce their suicidal ideations, and help them develop a healthy and positive outlook toward life, making this method worthy of clinical recommendation.

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