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1.
Arch Med Res ; 55(4): 103017, 2024 06.
Article in English | MEDLINE | ID: mdl-38937005

ABSTRACT

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editorial Board of the Archives of Medical Research after receiving a complaint reporting that the article was based on an unreliable or non-existent statistical method. After analyzing the complaint and carefully reviewing the article, the Editorial Board contacted the corresponding author following due process and received no response. The Editorial Board no longer has confidence in the article and therefore decided to retract the article. Apologies are offered to readers of the journal that this was not detected during the review process.

2.
Pharmacotherapy ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884415

ABSTRACT

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

3.
Eur J Med Res ; 29(1): 334, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38880878

ABSTRACT

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.


Subject(s)
Cognition , Genotype , Parkinson Disease , Humans , Parkinson Disease/genetics , Parkinson Disease/complications , Parkinson Disease/psychology , Parkinson Disease/physiopathology , Male , Female , Middle Aged , Aged , Cognition/physiology , Cognitive Dysfunction/genetics , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Apolipoproteins E/genetics , Amyloid beta-Peptides/cerebrospinal fluid , Apolipoprotein E4/genetics
4.
Ann Hematol ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886191

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.

5.
Cell Rep Med ; 5(6): 101592, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38843841

ABSTRACT

Environmental lipids are essential for fueling tumor energetics, but whether these exogenous lipids transported into cancer cells facilitate immune escape remains unclear. Here, we find that CD36, a transporter for exogenous lipids, promotes acute myeloid leukemia (AML) immune evasion. We show that, separately from its established role in lipid oxidation, CD36 on AML cells senses oxidized low-density lipoprotein (OxLDL) to prime the TLR4-LYN-MYD88-nuclear factor κB (NF-κB) pathway, and exogenous palmitate transfer via CD36 further potentiates this innate immune pathway by supporting ZDHHC6-mediated MYD88 palmitoylation. Subsequently, NF-κB drives the expression of immunosuppressive genes that inhibit anti-tumor T cell responses. Notably, high-fat-diet or hypomethylating agent decitabine treatment boosts the immunosuppressive potential of AML cells by hijacking CD36-dependent innate immune signaling, leading to a dampened therapeutic effect. This work is of translational interest because lipid restriction by US Food and Drug Administration (FDA)-approved lipid-lowering statin drugs improves the efficacy of decitabine therapy by weakening leukemic CD36-mediated immunosuppression.


Subject(s)
CD36 Antigens , Decitabine , Leukemia, Myeloid, Acute , Lipid Metabolism , Lipoproteins, LDL , CD36 Antigens/metabolism , CD36 Antigens/genetics , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Lipid Metabolism/drug effects , Decitabine/pharmacology , Decitabine/therapeutic use , Lipoproteins, LDL/metabolism , Animals , NF-kappa B/metabolism , Cell Line, Tumor , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/genetics , Mice , Signal Transduction/drug effects , Tumor Escape/drug effects , Drug Resistance, Neoplasm/drug effects , Toll-Like Receptor 4/metabolism , Acyltransferases/genetics , Immunity, Innate/drug effects , Mice, Inbred C57BL
6.
Article in English | MEDLINE | ID: mdl-38909990

ABSTRACT

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

7.
Front Microbiol ; 15: 1396663, 2024.
Article in English | MEDLINE | ID: mdl-38873155

ABSTRACT

Klebsiella pneumoniae (K. pneumoniae) infection and the rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. Polymyxin E (colistin), a group of cationic antimicrobial polypeptides, is currently one of the last resort treatment options against carbapenem-resistant Gram-negative pathogens. The effectiveness of colistin has been compromised due to its intensive use. This study found that fingolimod (FLD), a natural product derivative, exhibited a significant synergistic bactericidal effect on K. pneumoniae when combined with colistin, both in vitro and in vivo. The checkerboard method was employed to assess the in vitro synergistic effect of FLD with colistin. FLD enhanced the susceptibility of bacteria to colistin and lowered effectively minimum inhibitory concentrations (MIC) when compared to colistin MIC, and the fractional inhibitory concentrations (FIC) value was less than 0.3. The time-kill curve demonstrated that the combination treatment of FLD and colistin had significant bactericidal efficacy. The in vitro concurrent administration of colistin and FLD resulted in heightening membrane permeability, compromising cell integrity, diminishing membrane fluidity, and perturbing membrane homeostasis. They also induced alterations in membrane potential, levels of reactive oxygen species, and adenosine triphosphate synthesis, ultimately culminating in bacterial death. Moreover, the combination of FLD with colistin significantly influenced fatty acid metabolism. In the mouse infection model, the survival rate of mice injected with K. pneumoniae was significantly improved to 67% and pathological damage was significantly relieved with combination treatment of FLD and colistin when compared with colistin treatment. This study highlights the potential of FLD in combining with colistin for treating infections caused by MDR isolates of K. pneumoniae.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 768-773, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926965

ABSTRACT

OBJECTIVE: To analyze the prognostic value of del(1p32) in patients with newly diagnosed multiple myeloma (MM). METHODS: The clinical data of 341 newly diagnosed MM attended in Jiangsu Province Hospital were retrospective analyzed. Clinical characteristic combined with genetic features, especially del(1p32), were analyzed for survival and prognostic of patients. RESULTS: Among the 341 patients with newly diagnosed MM, 24(7.0%) patients were del(1p32) positive. The progression-free survival (PFS) and overall survival (OS) were significantly shorter in MM patients with del(1p32) than those without del(1p32) (PFS: P < 0.001;OS: P < 0.001). The COX proportional-hazards model showed that del (1p32) was an independent risk factor for PFS and OS of patients with MM. The patients with both 1q21 gain/amplification and del(1p32), as "double-hit chromosome 1", have worse prognosis than those with only 1q21 gain/amplification or only del(1p32) (PFS: P < 0.001; OS: P < 0.001). CONCLUSION: Del(1p32) is an independent risk factor for PFS and OS of patients with MM. Del(1p32) detection should be widely used in the prognostic analysis for newly diagnosed MM patients.


Subject(s)
Chromosomes, Human, Pair 1 , Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Prognosis , Retrospective Studies , Chromosomes, Human, Pair 1/genetics , Risk Factors , Chromosome Deletion , Proportional Hazards Models , Male , Female , Middle Aged
9.
Int J Biol Sci ; 20(7): 2640-2657, 2024.
Article in English | MEDLINE | ID: mdl-38725843

ABSTRACT

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , HMGA1a Protein , MTOR Inhibitors , Proto-Oncogene Protein c-ets-1 , Tacrolimus Binding Protein 1A , Animals , Humans , Mice , Cell Line, Tumor , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , HMGA1a Protein/metabolism , HMGA1a Protein/genetics , Mice, Nude , MTOR Inhibitors/pharmacology , MTOR Inhibitors/therapeutic use , Proto-Oncogene Protein c-ets-1/metabolism , Proto-Oncogene Protein c-ets-1/genetics , Signal Transduction/drug effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , Tacrolimus Binding Protein 1A/metabolism , Tacrolimus Binding Protein 1A/genetics , TOR Serine-Threonine Kinases/metabolism
10.
Leukemia ; 38(7): 1541-1552, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38750139

ABSTRACT

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Lymphoma, Large B-Cell, Diffuse , Mutation , Humans , Lymphoma, Large B-Cell, Diffuse/cerebrospinal fluid , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/diagnosis , Female , Male , Middle Aged , Biomarkers, Tumor/cerebrospinal fluid , Biomarkers, Tumor/genetics , Aged , Adult , Circulating Tumor DNA/cerebrospinal fluid , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Prognosis , Aged, 80 and over , Young Adult , Prospective Studies
11.
Plant Divers ; 46(3): 421-424, 2024 May.
Article in English | MEDLINE | ID: mdl-38798722

ABSTRACT

•Four newly recorded species of Podostemaceae from southern China were identified by molecular and morphological evidence.•17 plastomes of Podostemaceae were newly sequenced and two novel polymorphic barcodes (ccsA and ndhA) detected.•Our findings reveal greater species richness (15 species from five genera) of Podostemaceae in China and supply molecular resources for research on taxonomy and phylogenomics of this enigmatic aquatic family.

12.
Sci Rep ; 14(1): 10647, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724510

ABSTRACT

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.


Subject(s)
Body Weight , Moringa oleifera , Rats, Sprague-Dawley , Animals , Moringa oleifera/chemistry , Rats , Male , Body Weight/drug effects , Eating/drug effects , Female , Animal Feed/analysis , Diarrhea/chemically induced , Diarrhea/veterinary
13.
Pest Manag Sci ; 80(8): 4069-4073, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38563512

ABSTRACT

BACKGROUND: The tomato leafminer, Phthorimaea absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a destructive invasive pest that originated in South America and has spread within China since 2017. A rapid method for on-site identification of P. absoluta is urgently needed for interception of this pest across China. RESULTS: We developed a loop-mediated isothermal amplification (LAMP) technique to differentiate P. absoluta from Liriomyza sativae, Chromatomyia horticola, and Phthorimaea operculella using extracted genomic DNA, which was then refined to create an on-site LAMP diagnostic method that can be performed under field conditions without the need for laboratory equipment. CONCLUSION: In the present research, we developed an on-site diagnostic method for rapid differentiation of P. absoluta from other insects with similar morphology or damage characteristics in China. © 2024 Society of Chemical Industry.


Subject(s)
Introduced Species , Moths , Nucleic Acid Amplification Techniques , Animals , Moths/genetics , Nucleic Acid Amplification Techniques/methods , Larva , Molecular Diagnostic Techniques/methods , China
14.
Food Microbiol ; 121: 104525, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38637087

ABSTRACT

The lack of vitamin B12 in unprocessed plant-based foods can lead to health problems in strict vegetarians and vegans. The main aim of this study was to investigate the potential synergy of co-culturing Bifidobacterium animalis subsp. lactis and Propionibacterium freudenreichii in improving production of vitamin B12 and short-chain fatty acids in soy whey. Different strategies including mono-, sequential and simultaneous cultures were adopted. Growth, short-chain fatty acids and vitamin B12 were assessed throughout the fermentation while free amino acids, volatiles, and isoflavones were determined on the final day. P. freudenreichii monoculture grew well in soy whey, whereas B. lactis monoculture entered the death phase by day 4. Principal component analysis demonstrates that metabolic changes in both sequential cultures did not show drastic differences to those of P. freudenreichii monoculture. However, simultaneous culturing significantly improved vitamin B12, acetic acid and propionic acid contents (1.3 times, 5 times, 2.5 times, compared to the next highest treatment [sequential cultures]) in fermented soy whey relative to other culturing modes. Hence, co-culturing of P. freudenreichii and B. lactis would provide an alternative method to improve vitamin B12, acetic acid and propionic acid contents in fermented foods.


Subject(s)
Bifidobacterium animalis , Propionibacterium freudenreichii , Propionates , Propionibacterium freudenreichii/metabolism , Bifidobacterium animalis/metabolism , Whey , Vitamin B 12/analysis , Vitamin B 12/metabolism , Propionibacterium/metabolism , Fatty Acids, Volatile/metabolism , Fermentation , Acetic Acid/metabolism , Whey Proteins/metabolism , Vitamins/metabolism
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 639-642, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660879

ABSTRACT

Berberine, a traditional Chinese medicine, is an isoquinoline alkaloid extracted from the rhizome of Coptis chinensis. It has anti-inflammatory and antidiarrheal effects and is commonly used in the treatment of infections and gastrointestinal diseases. In recent years, studies have found that berberine can play a wide range of anti-cancer effects in the treatment of leukemia, lymphoma, multiple myeloma, etc. In hematologic malignancies, berberine can induce autophagy, promote apoptosis, regulate cell cycle, inhibit inflammatory response, cause oxidative damage to cancer cells and interact with miRNA to inhibit the proliferation, migration and colony formation of cancer cells. This paper will review the role and related mechanisms of berberine in hematological malignancies.


Subject(s)
Apoptosis , Berberine , Hematologic Neoplasms , Berberine/pharmacology , Humans , Hematologic Neoplasms/drug therapy , Apoptosis/drug effects , Autophagy/drug effects , Cell Proliferation/drug effects , Cell Cycle/drug effects , MicroRNAs
16.
Inorg Chem ; 63(18): 8462-8475, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38642052

ABSTRACT

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.


Subject(s)
Azabicyclo Compounds , Chelating Agents , Contrast Media , Gadolinium , Magnetic Resonance Imaging , Contrast Media/chemistry , Animals , Mice , Chelating Agents/chemistry , Chelating Agents/chemical synthesis , Gadolinium/chemistry , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Molecular Structure , Stereoisomerism , Humans , Female
17.
Mol Phylogenet Evol ; 196: 108084, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38688440

ABSTRACT

The tribe Collabieae (Epidendroideae, Orchidaceae) comprises approximately 500 species. Generic delimitation within Collabieae are confusing and phylogenetic interrelationships within the Collabieae have not been well resolved. Plastid genomes and nuclear internal transcribed spacer (ITS) sequences were used to estimate the phylogenetic relationships, ancestral ranges, and diversification rates of Collabieae. The results showed that Collabieae was subdivided into nine clades with high support. We proposed to combine Ancistrochilus and Pachystoma into Spathoglottis, merge Collabium and Chrysoglossum into Diglyphosa, and separate Pilophyllum and Hancockia as distinctive genera. The diversification of the nine clades of Collabieae might be associated with the uplift of the Himalayas during the Late Oligocene/Early Miocene. The enhanced East Asian summer monsoon in the Late Miocene may have promoted the rapid diversification of Collabieae at a sustained high diversification rate. The increased size of terrestrial pseudobulbs may be one of the drivers of Collabieae diversification. Our results suggest that the establishment and development of evergreen broadleaved forests facilitated the diversification of Collabieae.


Subject(s)
Orchidaceae , Phylogeny , Orchidaceae/genetics , Orchidaceae/classification , Forests , Genome, Plastid/genetics , Phylogeography , DNA, Ribosomal Spacer/genetics , Sequence Analysis, DNA , Asia , DNA, Plant/genetics
18.
Cancer Lett ; 591: 216877, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38615930

ABSTRACT

Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.


Subject(s)
Cell Proliferation , Fatty Acid Synthase, Type I , Lipid Metabolism , Lymphoma, Mantle-Cell , Protein-Arginine N-Methyltransferases , Proto-Oncogene Proteins c-myc , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/metabolism , Lymphoma, Mantle-Cell/pathology , Humans , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Fatty Acid Synthase, Type I/metabolism , Fatty Acid Synthase, Type I/genetics , Cell Line, Tumor , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 2/metabolism , Sterol Regulatory Element Binding Protein 2/genetics , Gene Expression Regulation, Neoplastic , Animals , Mice , Male , Prognosis , Female , Cholesterol/metabolism , CRISPR-Cas Systems , Metabolic Reprogramming
19.
Clin. transl. oncol. (Print) ; 26(3): 720-731, mar. 2024.
Article in English | IBECS | ID: ibc-230801

ABSTRACT

Purpose The International Extranodal Lymphoma Study Group (IELSG) score is widely used in clinical practice to stratify the risk of primary central nervous system lymphoma (PCNSL) patients. Our study aims to confirm and improve the IELSG score in PCNSL patients based on Chinese populations. Materials and methods A total of 79 PCNSL patients were retrospectively analyzed. All patients treated with high-dose methotrexate (HD-MTX)-based therapy collected clinical data. The receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values for the factors in IELSG score. Progression of disease (POD) at the most landmark time point was determine by Epanechnikov kernel and the area under the ROC curve (AUROC). Kaplan–Meier and multivariable regression methods were used to analyze survival data. Nomogram was generated for calculating the weight of each selected factor. Results The traditional IELSG score had no significant difference on OS and PFS except ECOG ≥ 2 and could not stratify the risk groups in PCNSL. The improved IELSG scoring system was established, which incorporated age ≥ 54 years, ECOG ≥ 2, deep brain structure, elevated CSF protein, and LDH/ULN > 0.75. On the other hand, POD18 was identified as a new powerful prognostic factor for PCNSL. In multivariate analysis, POD18 and the improved IELSG scoring system were independent prognostic factors for OS. Nomogram including the two significant variables showed the best performance (C-index = 0.828). Conclusions In this study, the IELSG score was improved and a new prognostic indicator POD18 was incorporated to construct a nomogram prognostic model, thereby further improving the predictive ability of the model (AU)


Subject(s)
Humans , Middle Aged , Composite Lymphoma/drug therapy , Composite Lymphoma/metabolism , Methotrexate/therapeutic use , Retrospective Studies , Treatment Outcome , Brain/metabolism , Prognosis
20.
Biomed Pharmacother ; 173: 116400, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484560

ABSTRACT

Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough. In this study, the mechanism and potential key pathways of AEE on improving hyperlipidemia in mice were investigated through the transcriptome and proteome study of ApoE-/- mice liver and the verification study on high-fat HepG2 cells. The results showed that AEE significantly decreased the serum TC and LDL-C levels of hyperlipidemia ApoE-/- mice, and significantly increased the enzyme activity of CYP7A1. After AEE intervention, the results of mice liver transcriptome and proteome showed that differential genes and proteins were enriched in lipid metabolism-related pathways. The results of RT-qPCR showed that AEE significantly regulated the expression of genes related to lipid metabolism in mice liver tissue. AEE significantly upregulated the protein expression of CYP7A1 in hyperlipidemia ApoE-/- mice liver tissue. The results in vitro showed that AEE significantly decreased the levels of TC and TG, and improved lipid deposition in high-fat HepG2 cells. AEE significantly increased the expression of CYP7A1 protein in high-fat HepG2 cells. AEE regulates the expression of genes related to lipid metabolism in high-fat HepG2 cells, mainly by FXR-SHP-CYP7A1 and FGF19-TFEB-CYP7A1 pathways. To sum up, AEE can significantly improve the hyperlipidemia status of ApoE-/- mice and the lipid deposition of high-fat HepG2 cells, and its main pathway is probably the bile acid metabolism-related pathway centered on CYP7A1.


Subject(s)
Hyperlipidemias , Mice , Rats , Animals , Hyperlipidemias/drug therapy , Hyperlipidemias/genetics , Hyperlipidemias/metabolism , Proteomics , Proteome/metabolism , Diet, High-Fat/adverse effects , Lipids , Lipid Metabolism/genetics , Gene Expression Profiling , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Liver/metabolism
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