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1.
Curr Cancer Drug Targets ; 24(5): 519-533, 2024.
Article in English | MEDLINE | ID: mdl-38804344

ABSTRACT

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine malignancy that originates from the parafollicular C cells of the thyroid gland. Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancer regions, which are critical regulators of tumorigenesis. However, the roles and regulatory mechanisms of eRNAs in MTC remain poorly understood. This study aims to identify key eRNAs regulating the malignant phenotype of MTC and to uncover transcription factors involved in the regulation of key eRNAs. METHODS: GSE32662 and GSE114068 were used for the identification of differentially expressed genes, eRNAs, enhancers and enhancer-regulated genes in MTC. Metascape and the transcription factor affinity prediction method were used for gene function enrichment and transcription factor prediction, respectively. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to assess the binding of histone H3 lysine 27 acetylation (H3K27ac)-enriched regions to anti- H3K27ac. RIP-qPCR was used to detect the binding between FOXQ1 and LINC00887. CCK8 and Transwell were performed to measure the proliferation and invasion of MTC cells, respectively. Intracellular reactive oxygen species (ROS) levels were quantified using a ROS assay kit. RESULTS: Four eRNAs (H1FX-AS1, LINC00887, MCM3AP-AS1 and A1BG-AS1) were screened, among which LINC00887 was the key eRNA promoting the proliferation and invasion of MTC cells. A total of 135 genes controlled by LINC00887-regulated enhancers were identified; among them, BCL2, PRDX1, SFTPD, TPO, GSS, RAD52, ZNF580, and ZFP36L1 were significantly enriched in the "ROS metabolic process" term. As a transcription factor regulating genes enriched in the "ROS metabolic process" term, FOXQ1 could recruit LINC00887. Overexpression of FOXQ1 restored LINC00887 knockdown-induced downregulation of GSS and ZFP36L1 transcription in MTC cells. Additionally, FOXQ1 overexpression counteracted the inhibitory effects of LINC00887 knockdown on the proliferation and invasion of MTC cells and the promotion of intracellular ROS accumulation induced by LINC00887 knockdown. CONCLUSION: LINC00887 was identified as a key eRNA promoting the malignant phenotype of MTC cells. The involvement of FOXQ1 was essential for LINC00887 to play a pro-tumorigenic role in MTC. Our findings suggest that the FOXQ1/LINC00887 axis is a potential therapeutic target for MTC.


Subject(s)
Carcinoma, Neuroendocrine , Cell Proliferation , Forkhead Transcription Factors , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding , Thyroid Neoplasms , Humans , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , RNA, Long Noncoding/genetics , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/metabolism , Enhancer Elements, Genetic , Disease Progression , Cell Line, Tumor , Cell Movement , Reactive Oxygen Species/metabolism , Enhancer RNAs
3.
Org Lett ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809099

ABSTRACT

A mild copper-catalyzed asymmetric Kinugasa/Michael addition cascade process is developed. The reaction of α, ß-unsaturated ester-tethered propiolamides with nitrones provides an efficient protocol for the construction of functionalized chiral 2,6-diazaspiro[3.4]octane-1,5-dione products in satisfactory yields and with high enantio- and diastereoselectivities.

4.
Front Cell Infect Microbiol ; 14: 1341545, 2024.
Article in English | MEDLINE | ID: mdl-38779561

ABSTRACT

Background: Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect. Methods: Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM. Results: The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts. Conclusion: As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.


Subject(s)
HIV Infections , Homosexuality, Male , RNA, Ribosomal, 16S , Saliva , Humans , Male , Saliva/microbiology , Saliva/virology , HIV Infections/microbiology , RNA, Ribosomal, 16S/genetics , Adult , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Microbiota , Metagenomics , CD4 Lymphocyte Count , Middle Aged , Young Adult , Sexual and Gender Minorities
5.
Org Lett ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767291

ABSTRACT

Genome mining of Emericella sp. XL-029 achieved a new type E sesterterpene synthase, EmES, which affored a novel bipolyhydroindenol sesterterpene, emerindanol A. Heterologous coexpression with the upstream P450 oxidase revealed C-4 hydroxylated product, emerindanol B. Notably, emerindanols A and B represented the first sesterterpenes featuring a unique 5/6-6/5 coupled ring system. EmES was postulated to initiate through C1-IV-V pathway and convert the fused ring intermediate into the final coupled ring product through a spiro skeleton.

6.
Int Immunopharmacol ; 134: 111997, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38759370

ABSTRACT

Cystitis is a common disease closely associated with urinary tract infections, and the specific mechanisms underlying its occurrence and development remain largely unknown. In this study, we discovered that IGFBP1 suppresses the occurrence and development of cystitis by stabilizing the expression of Umod through m6A modification, inhibiting the NF-κB and ERK signaling pathways. Initially, we obtained a bladder cystitis-related transcriptome dataset from the GEO database and identified the characteristic genes Umod and IGFBP1. Further exploration revealed that IGFBP1 in primary cells of cystitis can stabilize the expression of Umod through m6A modification. Overexpression of both IGFBP1 and Umod significantly inhibited cell apoptosis and the NF-κB and ERK signaling pathways, ultimately suppressing the production of pro-inflammatory factors. Finally, using a rat model of cystitis, we demonstrated that overexpression of IGFBP1 stabilizes the expression of Umod, inhibits the NF-κB and ERK signaling pathways, reduces the production of pro-inflammatory factors, and thus prevents the occurrence and development of cystitis. Our study elucidates the crucial role of IGFBP1 and Umod in cystitis and reveals the molecular mechanisms that inhibit the occurrence and development of cystitis. This research holds promise for offering new insights into the treatment of cystitis in the future.

7.
BMC Vet Res ; 20(1): 203, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755641

ABSTRACT

BACKGROUND: Avian influenza virus (AIV) not only causes huge economic losses to the poultry industry, but also threatens human health. Reverse transcription recombinase-aided amplification (RT-RAA) is a novel isothermal nucleic acid amplification technology. This study aimed to improve the detection efficiency of H5, H7, and H9 subtypes of AIV and detect the disease in time. This study established RT-RAA-LFD and real-time fluorescence RT-RAA (RF-RT-RAA) detection methods, which combined RT-RAA with lateral flow dipstick (LFD) and exo probe respectively, while primers and probes were designed based on the reaction principle of RT-RAA. RESULTS: The results showed that RT-RAA-LFD could specifically amplify H5, H7, and H9 subtypes of AIV at 37 °C, 18 min, 39 °C, 20 min, and 38 °C, 18 min, respectively. The sensitivity of all three subtypes for RT-RAA-LFD was 102 copies/µL, which was 10 ∼100 times higher than that of reverse transcription polymerase chain reaction (RT-PCR) agarose electrophoresis method. RF-RT-RAA could specifically amplify H5, H7, and H9 subtypes of AIV at 40 °C, 20 min, 38 °C, 16 min, and 39 °C, 17 min, respectively. The sensitivity of all three subtypes for RF-RT-RAA was 101 copies/µL, which was consistent with the results of real-time fluorescence quantification RT-PCR, and 100 ∼1000 times higher than that of RT-PCR-agarose electrophoresis method. The total coincidence rate of the two methods and RT-PCR-agarose electrophoresis in the detection of clinical samples was higher than 95%. CONCLUSIONS: RT-RAA-LFD and RF-RT-RAA were successfully established in this experiment, with quick response, simple operation, strong specificity, high sensitivity, good repeatability, and stability. They are suitable for the early and rapid diagnosis of Avian influenza and they have positive significance for the prevention, control of the disease, and public health safety.


Subject(s)
Chickens , Influenza A virus , Influenza in Birds , Nucleic Acid Amplification Techniques , Recombinases , Reverse Transcription , Animals , Influenza in Birds/virology , Influenza in Birds/diagnosis , Nucleic Acid Amplification Techniques/veterinary , Nucleic Acid Amplification Techniques/methods , Influenza A virus/genetics , Influenza A virus/classification , Influenza A virus/isolation & purification , Recombinases/metabolism , Sensitivity and Specificity , Poultry Diseases/virology , Poultry Diseases/diagnosis
8.
J Med Chem ; 67(10): 7973-7994, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38728549

ABSTRACT

Triple-negative breast cancer is a highly aggressive and heterogeneous breast cancer subtype characterized by early metastasis, poor prognosis, and high recurrence. Targeting histone citrullination-mediated chromatin dysregulation to induce epigenetic alterations shows great promise in TNBC therapy. We report the synthesis, optimization, and evaluation of a novel series of ß-carboline-derived peptidyl arginine deiminase 4 inhibitors that exhibited potent inhibition of TNBC cell proliferation. The most outstanding PAD4 inhibitor, compound 28, hindered the PAD4-H3cit-NET signaling pathway and inhibited the growth of solid tumors and pulmonary metastatic nodules in the 4T1 in situ mouse model. Furthermore, 28 improved the tumor immune microenvironment by reshaping neutrophil phenotype, upregulating the proportions of dendritic cells and M1 macrophages, and reducing the amount of myeloid-derived suppressor cells. In conclusion, our work offered 28 as an efficacious PAD4 inhibitor that exerts a combination of conventional chemotherapy and immune-boosting effects, which represents a potential therapy strategy for TNBC.


Subject(s)
Antineoplastic Agents , Carbolines , Neutrophils , Protein-Arginine Deiminase Type 4 , Triple Negative Breast Neoplasms , Tumor Microenvironment , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/immunology , Carbolines/pharmacology , Carbolines/chemistry , Carbolines/therapeutic use , Carbolines/chemical synthesis , Animals , Protein-Arginine Deiminase Type 4/antagonists & inhibitors , Female , Humans , Tumor Microenvironment/drug effects , Mice , Neutrophils/drug effects , Neutrophils/metabolism , Neutrophils/immunology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell Proliferation/drug effects , Mice, Inbred BALB C , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/therapeutic use , Phenotype , Structure-Activity Relationship
9.
ACS Appl Mater Interfaces ; 16(20): 26537-26546, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38739859

ABSTRACT

Water-stable organic radicals are promising photothermal conversion candidates for photothermal therapy (PTT). However, organic radicals are usually unstable in biological environments, which greatly hinders their wide application. Here, we have developed a chaotropic effect-based and photoinduced water-stable supramolecular radical (MB12-2) for efficient antibacterial PTT. The supramolecular radical precursor MB12-1 was constructed by the chaotropic effect between closo-dodecaborate cluster (B12H122-) and N,N'-dimethylated dipyridinium thiazolo [5,4-d] thiazole (MPT2+). Subsequently, with triethanolamine (TEOA) serving as an electron donor, MB12-1 could transform to its radical form MB12-2 through photoinduced electron transfer (PET) under 435-nm laser irradiation. The N2 adsorption-desorption analysis confirmed that MB12-2 was tightly packed through the introduction of B12H122-, which effectively enhanced its stability via a spatial site-blocked effect. Moreover, the half-life of MB12-2 in water was calculated through ultraviolet-visible light (UV-vis) absorption spectra results for periods as long as 20 days. In addition, in the skin infection model, MB12-2, as a wound dressing, showed remarkable photothermal antibacterial activity (>97%) under 660-nm laser irradiation and promoted wound healing. This study presents a simple method for designing long-term water-stable supramolecular radicals, offering a novel avenue for noncontact treatments for bacterial infections.


Subject(s)
Anti-Bacterial Agents , Photothermal Therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Animals , Water/chemistry , Mice , Free Radicals/chemistry , Boron/chemistry , Boron/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects
10.
Eur J Neurol ; : e16326, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709145

ABSTRACT

BACKGROUND AND PURPOSE: The causal association between inflammatory cytokines and the development of intracranial aneurysm (IA), unruptured IA (uIA) and subarachnoid hemorrhage (SAH) lacks clarity. METHODS: The summary-level datasets for inflammatory cytokines were extracted from a genome-wide association study of the Finnish Cardiovascular Risk in Young Adults Study and the FINRISK survey. The summary statistics datasets related to IA, uIA and SAH were obtained from the genome-wide association study meta-analysis of the International Stroke Genetics Consortium and FinnGen Consortium. The primary method employed for analysis was inverse variance weighting (false discovery rate), supplemented by sensitivity analyses to address pleiotropy and enhance robustness. RESULTS: In the International Stroke Genetics Consortium, 10, six and eight inflammatory cytokines exhibited a causal association with IA, uIA and SAH, respectively (false discovery rate, p < 0.05). In FinnGen datasets, macrophage Inflammatory Protein-1 Alpha (MIP_1A), MIP_1A and interferon γ-induced protein 10 (IP_10) were verified for IA, uIA and SAH, respectively. In the reverse Mendelian randomization analysis, the common cytokines altered by uIA and SAH were vascular endothelial growth factor (VEGF), MIP_1A, IL_9, IL_10 and IL_17, respectively. The meta-analysis results show that MIP_1A and IP_10 could be associated with the decreased risk of IA, and MIP_1A and IP_10 were associated with the decreased risk of uIA and SAH, respectively. Notably, the levels of VEGF, MIP_1A, IL_9, IL_10 and TNF_A were increased with uIA. Comprehensive heterogeneity and pleiotropy analyses confirmed the robustness of these results. CONCLUSION: Our study unveils a bidirectional association between inflammatory cytokines and IA, uIA and SAH. Further investigations are essential to validate their relationship and elucidate the underlying mechanisms.

11.
Front Bioeng Biotechnol ; 12: 1378031, 2024.
Article in English | MEDLINE | ID: mdl-38784765

ABSTRACT

Background: Abnormal, excessive, and repetitive knee load is a critical risk factor for osteoarthritis (OA). The gastrocnemius muscle-tendon unit (MTU) interacts with foot biomechanics and is vital in cushioning the knee load. Abnormal gastrocnemius activation and plantar pressure during walking in patients with knee OA may negatively affect gastrocnemius MTU stiffness, increasing knee load. Few studies investigated the relationship between gastrocnemius MTU stiffness and plantar pressure. This study aimed to evaluate the changes in gastrocnemius MTU stiffness in patients with knee OA and their correlations with plantar pressure and clinical symptoms. Methods: Thirty women patients with unilateral knee OA and 30 healthy women participants were recruited. Shear wave elastography was used to quantify gastrocnemius MTU stiffness in ankle resting and anatomical 0° positions, defined as natural and neutral positions in this study. A plantar pressure analysis system was used to collect the plantar pressure parameters on the symptomatic side in patients with knee OA. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) scores were used to measure the severity of clinical symptoms. Results: Medial and lateral gastrocnemius (MG and LG) stiffness on both the asymptomatic and symptomatic sides in patients with knee OA was increased compared with that in healthy participants. The MG and LG optimal cutoff stiffness in the natural position was 15.73 kPa and 14.25 kPa, respectively. The optimal cutoff stiffness in the neutral position was 36.32 kPa and 25.43 kPa, respectively, with excellent sensitivity and specificity. The MG and LG stiffness were positively correlated with the percentages of anterior and medial plantar pressure and negatively correlated with the length of pressure center path. The LG and MG were significantly correlated with WOMAC and VAS scores. Conclusion: Patients with knee OA have increased gastrocnemius muscle stiffness, closely related to plantar pressure and clinical symptoms. Monitoring the gastrocnemius muscle in patients with knee OA can provide an essential basis for its prevention and treatment.

12.
Gels ; 10(5)2024 May 09.
Article in English | MEDLINE | ID: mdl-38786241

ABSTRACT

Metal-coordinated hydrogels are becoming increasingly popular in the biomedical field due to their unique properties. However, the mechanism behind gel forming involving metal ions is not yet fully understood. In this work, terahertz spectroscopy was used to investigate the role of interfacial water in the gelation process of copper ion-coordinated poly(vinyl alcohol) hydrogels. The results showed that the binding of copper ions could alter the interfacial hydration dynamics of the poly(vinyl alcohol) polymers. Combined with the results of differential scanning calorimetry (DSC), we propose a possible hydration layer-mediated mechanism for the formation of cooper ion-coordinated hydrogel during the freeze-thaw cycle. These results highlight the value of terahertz spectroscopy as a sensor for studying the hydration process in hydrogels and provide an important clue for understanding the mechanism of hydrogelation in ion-coordinated hydrogels.

13.
Eur J Med Chem ; 272: 116471, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38704945

ABSTRACT

Honokiol (HNK) is a typical natural biphenyl polyphenol compound. It has been proven to have a wide range of biological activities, including pharmacological effects such as anti-cancer, anti-inflammatory, neuroprotective, and antimicrobial. However, due to the poor stability, water solubility, and bioavailability of HNK, HNK has not been used in clinical treatment. This article reviews the latest research on the pharmacological activity of HNK and summarizes the HNK derivatives designed and improved by several researchers. Reviewing these contents could promote the research process of HNK and guide the design of better HNK derivatives for clinical application in the future.


Subject(s)
Biphenyl Compounds , Lignans , Lignans/pharmacology , Lignans/chemistry , Lignans/chemical synthesis , Biphenyl Compounds/pharmacology , Biphenyl Compounds/antagonists & inhibitors , Biphenyl Compounds/chemistry , Humans , Structure-Activity Relationship , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/chemical synthesis , Molecular Structure , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Allyl Compounds , Phenols
14.
Phytochemistry ; 223: 114120, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705265

ABSTRACT

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.


Subject(s)
Anti-Inflammatory Agents , Artemisia , Cyclopentanes , Nitric Oxide , Oxylipins , Sesquiterpenes , Artemisia/chemistry , Mice , Oxylipins/pharmacology , Oxylipins/chemistry , Oxylipins/isolation & purification , Animals , RAW 264.7 Cells , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Cyclopentanes/chemistry , Cyclopentanes/pharmacology , Cyclopentanes/isolation & purification , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Molecular Structure , Structure-Activity Relationship , Molecular Docking Simulation , Humans , Dose-Response Relationship, Drug , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Plant Leaves/chemistry , Drug Screening Assays, Antitumor
15.
Int J Soc Psychiatry ; : 207640241250312, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38803229

ABSTRACT

BACKGROUND: Prior researches have established that suicide and non-suicidal self-injury (NSSI) exhibit familial transmission patterns. However, the extent to which these patterns vary across different income levels remains unclear, as well as the specific factors that influence them. This study aimed to explore these questions. METHODS: We analyzed data from 13,988 parent-child pairs in Chongqing, China, where the children were aged from 7 to 12 years old. Six income levels were considered, and the children's depression and anxiety symptoms were assessed using standardized scales (the Center for Epidemiological Studies Depression Scale for Children, [CES-DC], and the Screen for Child Anxiety Related Emotional Disorders [SCARED], respectively). Binary logistic regression analysis was employed to examine the transmission of suicide and NSSI across different income levels. RESULTS: Familial transmission of suicide was significant difference in all income levels except the highest, while familial transmission of NSSI was significant difference in all income levels except the lowest. Notably, in both low- and high-income levels, suicide and NSSI transmissions primarily occurred among male children, mothers with higher education, and children who spent long time with their mothers. Additionally, the transmissions were mediated partially or entirely by children's depression and anxiety symptoms. LIMITATIONS: Future studies should investigate the separate effects of fathers' and mothers' suicide and NSSI histories on familial transmission patterns. CONCLUSION: The familial transmissions of suicide and NSSI exhibited distinct patterns across different income levels.

16.
Contemp Clin Trials Commun ; 39: 101299, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38720913

ABSTRACT

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism. Methods and analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment. Discussion: Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated. Ethics and dissemination: Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. Trial registration: NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023.

17.
Transl Androl Urol ; 13(4): 537-547, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38721285

ABSTRACT

Background: Inflammation, fibrosis and autophagy represent closely related factors associated with the pathogenesis of diabetes mellitus erectile dysfunction (DMED). In this study, the therapeutic effect of nitro-oleic acid (NO2-OA) in a streptozotocin-induced rat model of DMED was evaluated. Methods: Sixty rats were randomly divided into four groups: control, DMED, DMED + Vehicle and DMED + NO2-OA. DMED was induced by intraperitoneal injection of streptozotocin in male rats. Blood glucose and body weight were measured every 2 weeks. After 4 weeks of NO2-OA treatment, erectile function was measured by electrical stimulation of cavernous nerve (CN). Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence and Masson's trichrome staining were used to verify the related factors and protein expression levels. Results: We found that NO2-OA could significantly increase erectile pressure in the corpus cavernosum of DMED rats. Results of western blot, confocal immunofluorescence and qRT-PCR assays revealed that NO2-OA significantly reduced inflammatory factors and the expression of nuclear factor kappa B (NF-κB). In addition, Masson staining results indicated that NO2-OA significantly reduced the display of fibrotic tissue in the corpus cavernosum. These beneficial effects may be related to reductions in the expression of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) and the increase in the expression of α-smooth muscle actin (α-SMA). Finally, NO2-OA treatment increased the expression of the autophagy marker, LC3, while P62 was decreased, effects suggesting that one of the underlying mechanisms of NO2-OA may involve an activation of the PI3K/AKT/mTOR pathway to enhance the capacity for autophagy within this tissue. Conclusions: NO2-OA enhances erectile function within a rat model of DMED by inhibiting inflammation and fibrosis along with activating autophagy.

18.
Sci China Life Sci ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38748354

ABSTRACT

Dynamic crosstalk between the embryo and mother is crucial during implantation. Here, we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium, identifying 4 different lineages in embryos and 13 cell types in the endometrium. Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations, showing development from undifferentiated trophectoderm to polar and mural trophectoderm. Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation. Then, we developed a novel tool, ExtraCellTalk, generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells. These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.

19.
J Glob Health ; 14: 04078, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38666515

ABSTRACT

Background: The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). Results: We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. Conclusions: People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. Registration: PROSPERO (CRD42021255508).


Subject(s)
Cardiovascular Diseases , HIV Infections , Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/complications , Cardiovascular Diseases/epidemiology , Risk Factors , Heart Disease Risk Factors
20.
ACS Appl Mater Interfaces ; 16(17): 22066-22078, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38629710

ABSTRACT

Development of crystalline porous materials for selective CO2 adsorption and storage is in high demand to boost the carbon capture and storage (CCS) technology. In this regard, we have developed a ß-keto enamine-based covalent organic framework (VM-COF) via the Schiff base polycondensation technique. The as-synthesized VM-COF exhibited excellent thermal and chemical stability along with a very high surface area (1258 m2 g-1) and a high CO2 adsorption capacity (3.58 mmol g-1) at room temperature (298 K). The CO2/CH4 and CO2/H2 selectivities by the IAST method were calculated to be 10.9 and 881.7, respectively, which were further experimentally supported by breakthrough analysis. Moreover, theoretical investigations revealed that the carbonyl-rich sites in a polymeric backbone have higher CO2 binding affinity along with very high binding energy (-39.44 KJ mol-1) compared to other aromatic carbon-rich sites. Intrigued by the best CO2 adsorption capacity and high CO2 selectivity, we have utilized the VM-COF for biogas purification produced by the biofermentation of municipal waste. Compared with the commercially available activated carbon, VM-COF exhibited much better purification ability. This opens up a new opportunity for the creation of functionalized nanoporous materials for the large-scale purification of waste-generated biogases to address the challenges associated with energy and the environment.

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