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1.
Sci Rep ; 14(1): 15358, 2024 07 04.
Article in English | MEDLINE | ID: mdl-38965390

ABSTRACT

Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system and inflammation intricately entwined in its pathogenesis. This study endeavors to elucidate gender-specific patterns in immune cell infiltration and diverse forms of cell demise within the AS milieu. The aim is to refine the diagnosis and treatment of gender-specific AS patients, thereby advancing patient outcomes. In the pursuit of our investigation, two datasets (GSE25101 and GSE73754) pertinent to ankylosing spondylitis (AS) were meticulously collected and normalized from the GEO database. Employing the CIBERSORT algorithm, we conducted a comprehensive analysis of immune cell infiltration across distinct demographic groups and genders. Subsequently, we discerned differentially expressed genes (DEGs) associated with various cell death modalities in AS patients and their healthy counterparts. Our focus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female patients. Leveraging machine learning (ML) methodologies, we formulated disease prediction models employing cell death-related DEGs (CDRDEGs) and identified biomarkers intertwined with cell death in AS. Relative to healthy controls, a myriad of differentially expressed genes (DEGs) linked to cell death surfaced in AS patients. Among AS patients, 82 FRDEGs, 29 CRDEGs, 54 AURDEGs, 21 ARDEGs, and 74 PRDEGs were identified. In male AS patients, these numbers were 78, 33, 55, 24, and 94, respectively. Female AS patients exhibited 66, 41, 40, 17, and 82 DEGs in the corresponding categories. Additionally, 36 FRDEGs, 14 CRDEGs, 19 AURDEGs, 10 ARDEGs, and 36 PRDEGs exhibited differential expression between male and female AS patients. Employing machine learning techniques, LASSO, RF, and SVM-RFE were employed to discern key DEGs related to cell death (CDRDDEGs). The six pivotal CDRDDEGs in AS patients, healthy controls, were identified as CLIC4, BIRC2, MATK, PKN2, SLC25A5, and EDEM1. For male AS patients, the three crucial CDRDDEGs were EDEM1, MAP3K11, and TRIM21, whereas for female AS patients, COX7B, PEX2, and RHEB took precedence. Furthermore, the trio of DDX3X, CAPNS1, and TMSB4Y emerged as the key CDRDDEGs distinguishing between male and female AS patients. In the realm of immune correlation, the immune infiltration abundance in female patients mirrored that of healthy controls. Notably, key genes exhibited a positive correlation with T-cell CD4 memory activation when comparing male and female patient samples. This study engenders a more profound comprehension of the molecular underpinnings governing immune cell infiltration and cell death in ankylosing spondylitis (AS). Furthermore, the discernment of gender-specific disparities among AS patients underscores the clinical significance of these findings. By identifying DEGs associated with diverse cell death modalities, this study proffers invaluable insights into potential clinical targets for AS patients, taking cognizance of gender-specific nuances. The identification of gender-specific biological targets lays the groundwork for the development of tailored diagnostic and therapeutic strategies, heralding a pivotal step toward personalized care for AS patients.


Subject(s)
Biomarkers , Spondylitis, Ankylosing , Humans , Spondylitis, Ankylosing/genetics , Spondylitis, Ankylosing/immunology , Spondylitis, Ankylosing/pathology , Male , Female , Sex Factors , Gene Expression Profiling , Apoptosis/genetics , Sex Characteristics
3.
Int J Surg ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857504

ABSTRACT

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in cancer tissue. The lack of specific biomarkers makes the diagnosis and prognosis of TNBC challenging. METHOD: A comprehensive literature review and bibliometric analysis was performed using CiteSpace, VOSviewer and Scimago Graphica. RESULTS: TNBC biomarker research has been growing rapidly in recent years, reflecting the enormous academic interest in TNBC biomarker research. A total of 127 journals published relevant studies and 1749 authors were involved in the field, with developed countries such as the United States, France, and the United Kingdom contributing greatly to the field. Collaborative network analysis found that the research in this field has not yet formed good communication and interaction, and the partnership should be strengthened in the future in order to promote the in-depth development of TNBC biomarker research. Comprehensive analysis of keywords and co-cited literature, etc. found that TNBC biomarker research mainly focuses on immune checkpoint markers, microenvironment-related markers, circulating tumour DNA, metabolic markers, genomics markers and so on. These research hotspots will help to better understand the molecular characteristics and biological processes of TNBC, and provide more accurate biomarkers for its diagnosis, treatment and prognosis. CONCLUSIONS: The bibliometric analysis highlighted global trends and key directions in TNBC biomarker research. Future developments in TNBC biomarker research are likely to be in the direction of multi-omics integration, meticulous study of the microenvironment, targeted therapeutic biomarkers, application of liquid biopsy, application of machine learning and artificial intelligence, and individualised therapeutic strategies. Young scholars should learn and collaborate across disciplines, pay attention to new technologies and methods, improve their data analysis skills, and continue to follow up on the latest research trends in order to meet the challenges and opportunities in the field of TNBC biomarkers.

4.
Front Psychiatry ; 15: 1391535, 2024.
Article in English | MEDLINE | ID: mdl-38903637

ABSTRACT

Background and objectives: Major Depressive Disorder (MDD) is one of the most prevalent and debilitating health conditions worldwide. Previous studies have reported a link between metabolic dysregulation and MDD. However, evidence for a causal relationship between blood metabolites and MDD is lacking. Methods: Using a two-sample bidirectional Mendelian randomization analysis (MR), we assessed the causal relationship between 1,400 serum metabolites and Major Depressive Disorder (MDD). The Inverse Variance Weighted method (IVW) was employed to estimate the causal association between exposures and outcomes. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode methods were used as supplementary approaches for a comprehensive appraisal of the causality between blood metabolites and MDD. Pleiotropy and heterogeneity tests were also conducted. Lastly, the relevant metabolites were subjected to metabolite function analysis, and a reverse MR was implemented to explore the potential influence of MDD on these metabolites. Results: After rigorous screening, we identified 34 known metabolites, 13 unknown metabolites, and 18 metabolite ratios associated with Major Depressive Disorder (MDD). Among all metabolites, 33 were found to have positive associations, and 32 had negative associations. The top five metabolites that increased the risk of MDD were the Arachidonate (20:4n6) to linoleate (18:2n6) ratio, LysoPE(18:0/0:0), N-acetyl-beta-alanine levels, Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio, Glutaminylglutamine, and Threonine to pyruvate ratio. Conversely, the top five metabolites that decreased the risk of MDD were N6-Acetyl-L-lysine, Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] ratio, Methionine to phosphate ratio, Pregnanediol 3-O-glucuronide, and 6-Oxopiperidine-2-carboxylic acid. Metabolite function enrichment was primarily concentrated in pathways such as Bile Acid Biosynthesis (FDR=0.177), Glutathione Metabolism (FDR=0.177), Threonine, and 2-Oxobutanoate Degradation (FDR=0.177). In addition, enrichment was noted in pathways like Valine, Leucine, and Isoleucine Biosynthesis (p=0.04), as well as Ascorbate and Aldarate Metabolism (p=0.04). Discussion: Within a pool of 1,400 blood metabolites, we identified 34 known metabolites and 13 unknown metabolites, as well as 18 metabolite ratios associated with Major Depressive Disorder (MDD). Additionally, three functionally enriched groups and two metabolic pathways were selected. The integration of genomics and metabolomics has provided significant insights for the screening and prevention of MDD.

5.
Eur J Dermatol ; 34(2): 144-149, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38907544

ABSTRACT

Hydroa vacciniforme lymphoproliferative disorder (HVLPD) is a rare disease related to Epstein-Barr virus (EBV), mainly in children, and is an EBV-associated cutaneous T and natural killer (NK) cell lymphoproliferative disorder. The disorder in some patients may progress to EBV-associated systemic T or NK-cell lymphoma. To summarize the characteristics of HVLPD in Chinese paediatric patients and to examine the risk factors indicating poor prognosis. We performed a retrospective analysis of patients with HVLPD from the Department of Dermatology, Beijing Children's Hospital. Based on diagnosis, medical history, examination results, and immunophenotype, we analysed HVLPD in 42 paediatric cases in order to examine the clinical features, prognoses, and risk factors. Forty-two paediatric patients were enrolled, with a median onset age of five years. All patients presented with papulovesicular lesions, and 32 systemic HVLPD (sHVLPD) patients had systemic symptoms, including fever, lymphadenopathy, hepatomegaly, splenomegaly, and liver dysfunction. Of the sHVLPD cases, 13 also had severe mosquito bite allergy (SMBA). Twenty-five cases were T-type, and nine were CD56+-dominant type. Follow-up data showed that 12 patients had complete remission, and three patients died. SMBA is a risk factor for disease progression in patients with HVLPD, and the pathological CD56+-dominant phenotype is associated with poor prognosis.


Subject(s)
Hydroa Vacciniforme , Humans , Retrospective Studies , Male , Hydroa Vacciniforme/virology , Hydroa Vacciniforme/pathology , Female , Child, Preschool , Child , Infant , Adolescent , Prognosis , Lymphoproliferative Disorders/virology , Lymphoproliferative Disorders/pathology , Epstein-Barr Virus Infections/complications , Risk Factors , China/epidemiology , Herpesvirus 4, Human/isolation & purification , Hepatomegaly/virology
6.
J Agric Food Chem ; 72(23): 13228-13239, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38810088

ABSTRACT

Limited alliinase resources cause difficulties in the biosynthesis of thiosulfinates (e.g., allicin), restricting their applications in the agricultural and food industries. To effectively biosynthesize thiosulfinates, this study aimed to excavate bacterial alliinase resources and elucidate their catalytic properties. Two bacterial cystathionine ß-lyases (MetCs) possessing high alliinase activity (>60 U mg -1) toward L-(-)-alliin were identified from Allium sativum rhizosphere isolates. Metagenomic exploration revealed that cystathionine ß-lyase from Bacillus cereus (BcPatB) possessed high activity toward both L-(±)-alliin and L-(+)-alliin (208.6 and 225.1 U mg -1), respectively. Although these enzymes all preferred l-cysteine S-conjugate sulfoxides as substrates, BcPatB had a closer phylogenetic relationship with Allium alliinases and shared several similar features with A. sativum alliinase. Interestingly, the Trp30Ile31Ala32Asp33 Met34 motif in a cuspate loop of BcPatB, especially sites 31 and 32 at the top of the motif, was modeled to locate near the sulfoxide of L-(+)-alliin and is important for substrate stereospecificity. Moreover, the stereoselectivity and activity of mutants I31V and A32G were higher toward L-(+)-alliin than those of mutant I31L/D33E toward L-(-)-alliin. Using bacterial alliinases and chemically synthesized substrates, we obtained thiosulfinates with high antimicrobial and antinematode activities that could provide insights into the protection of crops and food.


Subject(s)
Bacterial Proteins , Garlic , Substrate Specificity , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Garlic/chemistry , Garlic/enzymology , Garlic/genetics , Sulfinic Acids/chemistry , Sulfinic Acids/metabolism , Bacillus cereus/enzymology , Bacillus cereus/genetics , Bacillus cereus/metabolism , Disulfides/chemistry , Disulfides/metabolism , Phylogeny , Stereoisomerism , Amino Acid Sequence , Bacteria/enzymology , Bacteria/genetics , Bacteria/classification , Bacteria/metabolism , Kinetics , Carbon-Sulfur Lyases/metabolism , Carbon-Sulfur Lyases/genetics , Carbon-Sulfur Lyases/chemistry , Cysteine/analogs & derivatives
7.
J Affect Disord ; 361: 17-23, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38815765

ABSTRACT

BACKGROUND: Depression is linked to obesity. The body roundness index (BRI) provides a more accurate assessment of body and visceral fat levels than the body mass index or waist circumference. However, the association between BRI and depression is unclear. Therefore, we investigated this relationship using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: In this population-based cross-sectional study, data from 18,654 adults aged ≥20 years from the NHANES 2011-2018 were analyzed. Covariates, including age, gender, race/ethnicity, education level, marital status, poverty-income ratio, alcohol status, smoking status, hypertension, diabetes mellitus, cardiovascular disease, energy intake, physical activity, total cholesterol, and triglycerides were adjusted in multivariable logistic regression models. In addition, smooth curve fitting, subgroup analysis, and interaction testing were conducted. RESULTS: After adjusting for covariates, BRI was positively correlated with depression. For each one-unit increase in BRI, the prevalence of depression increased by 8 % (odds ratio = 1.08, 95 % confidence interval = 1.05-1.10, P < 0.001). LIMITATIONS: As this was a cross-sectional study, we could not determine a causal relationship between BRI and depression. Patients with depression in this study were not clinically diagnosed with major depressive disorder. CONCLUSION: BRI levels were positively related to an increased prevalence of depression in American adults. BRI may serve as a simple anthropometric index to predict depression.

8.
J Transl Med ; 22(1): 437, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720345

ABSTRACT

BACKGROUND: Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. METHODS: FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. RESULTS: The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. CONCLUSION: In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials.


Subject(s)
Durapatite , Glycolysis , Macrophages , Oxidative Phosphorylation , Rats, Sprague-Dawley , Animals , Durapatite/chemistry , Macrophages/metabolism , Macrophages/drug effects , Oxidative Phosphorylation/drug effects , Glycolysis/drug effects , Rats , Swine , Cell Proliferation/drug effects , Male , Osteogenesis/drug effects , Skull/pathology , Skull/drug effects , Mice , Cellular Microenvironment/drug effects , RAW 264.7 Cells , Bone and Bones/metabolism , Bone and Bones/drug effects
9.
J Psychiatr Res ; 175: 218-226, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38744161

ABSTRACT

BACKGROUND: Ketamine, electroconvulsive therapy (ECT), and their combination are effective for treating severe depression, but few large-scale studies have compared these. METHODS: We searched databases for randomized controlled trials (RCTs) using ketamine, ECT, ketamine + ECT, or placebo for severe depression. Standardized measures were efficacy outcomes. Risk of bias was assessed. Stata and ADDIS were used for network meta-analysis (NMA) comparing efficacy and adverse reactions post-treatment. This study was registered on PROSPERO (CRD42023476740). RESULTS: 17 RCTs with 1370 patients were included. NMA showed ECT and ketamine improved Hamilton Depression Rating Scale (HDRS) versus placebo; other comparisons not significant. Rank probabilities showed highest probability for ECT, followed by ketamine + ECT, ketamine, placebo. No differences in Montgomery-Asberg Depression Rating Scale (MADRS); highest rank probability again for ECT, followed by ketamine + ECT, ketamine, placebo. CONCLUSIONS: Analysis suggests ECT superior to ketamine and their combination for improving depressive severity, but individualized treatment selection warranted. Higher adverse reactions with ketamine + ECT need further study for optimized combined use.

10.
Anim Nutr ; 17: 208-219, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38800733

ABSTRACT

The intake of high-fat diets (HFD) has been shown to diminish the muscle quality of aquatic animals. Sanguinarine, as an excellent additive, exhibits the capability to reduce fat deposition and alleviate inflammation. However, its role in the muscle quality reduction caused by HFD remains unclear. An eight-week trial was conducted to investigate the impacts of dietary supplementation of sanguinarine at 1200 µg/kg (HFDS; crude fat = 10%) on the muscle quality of grass carp (Ctenopharyngodon idellus) in comparison to a basic diet (CON, crude fat = 5%). Each group had 3 replicates, with 40 fish per replicate. This experiment employed one-way ANOVA and Duncan's multiple comparisons of the means. The results showed that the HFD exhibited lower growth performance, reduced protein deposition, myofiber diameter, and muscle hardness, coupled with higher levels of fat deposition and inflammation when compared with the CON. However, HFDS improved growth performance (P < 0.05), fat metabolism (ppar-α ( P = 0.001), lpl (P < 0.001), atgl (P < 0.001), and cpt1 (P = 0.001) expression exhibited a significant elevation), protein deposition (the protein and mRNA levels of AKT (P = 0.004), PI3K (P = 0.027), TOR (P = 0.005), and P70S6K (P = 0.007) demonstrated a marked increase), myofiber diameter, muscle hardness, and the total content of eicosapentaenoic acid and docosahexaenoic acid. Furthermore, the HFDS reduced oxidative damage caused by fat deposition by significantly downregulating nf-κb (P < 0.001), il-1ß (P < 0.001), il-6 (P < 0.001), il-8 (P = 0.003), and tnf-α (P < 0.001) expression and markedly upregulated nrf2 (P < 0.001), gpx4 (P < 0.001), cat (P < 0.001), sod (P < 0.001), and gr (P = 0.003) expression. The findings from this study suggest that sanguinarine has the potential to alleviate the adverse effects of HFD on growth and muscle quality, providing a theoretical foundation for its practical implementation.

11.
J Affect Disord ; 358: 61-69, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38705524

ABSTRACT

BACKGROUND: Depression, a prevalent mental disorder, has shown an increasing trend in recent years, imposing a significant burden on health and society. Adequate sleep has been proven to reduce the incidence of depression. This study seeks to explore how Weekend Catch-up Sleep (WCS) is connected with the prevalence of depression in the American population. METHODS: The National Health and Nutrition Examination Survey (NHANES) provides representative data for the U.S. POPULATION: We utilized data from the 2017-2018 and 2019-2020 cycles. Depression was operationally defined as a PHQ-9 score exceeding 10. WCS duration was categorized into five groups: no change in sleep duration (=0 h), decreased sleep duration (<0), short catch-up sleep duration (>0 h, ≤1 h), moderate catch-up sleep duration (>1 h, <2 h), and long catch-up sleep duration (≥2 h). RESULTS: Among the 8039 individuals, the distribution of WCS duration was as follows: no change (WCS = 0 h) in 2999 individuals (37.3 %), decreased sleep (WCS < 0 h) in 1199 individuals (14.9 %), short catch-up sleep (0 h < WCS ≤ 1 h) in 1602 individuals (19.9 %), moderate catch-up sleep (1 h < WCS < 2 h) in 479 individuals (6.0 %), and long catch-up sleep (WCS ≥ 2 h) in 1760 individuals (21.9 %). Acting by adjustment for all covariates in a multiple regression analysis, we discovered that persons with 1 to 2 h of weekend catch-up sleep had a substantially low prevalence of depression concerning those with WCS = 0 (OR 0.22, 95 % CI 0.08-0.59, P = 0.007). CONCLUSION: The prevalence of depression in individuals engaging in weekend catch-up sleep for 1 to 2 h is lower than those who do not catch up on weekends. This discovery on the treatment and prevention of depression provides a new perspective. However, further prospective research and clinical trials are needed for a comprehensive investigation.


Subject(s)
Depression , Nutrition Surveys , Sleep , Humans , Female , Male , Adult , United States/epidemiology , Middle Aged , Depression/epidemiology , Prevalence , Sleep/physiology , Young Adult , Time Factors , Aged
12.
J Affect Disord ; 358: 211-221, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38705530

ABSTRACT

BACKGROUND: Neuroinflammation is involved in the advancement of depression. Du-moxibustion can treat depression. Here, we explored whether Du-moxibustion could alleviate neuroglia-associated neuro-inflammatory process in chronic unpredictable mild stress (CUMS) mice. METHODS: C57BL/6J mice were distributed into five groups. Except for the CON group, other four groups underwent CUMS for four consecutive weeks, and Du-moxibustion was given simultaneously after modeling. Behavioral tests were then carried out. Additionally, Western blot was conducted to measure the relative expression levels of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). Immunofluorescence was employed to evaluate the positive cells of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were analyzed using an ELISA assay. RESULTS: We found that CUMS induced depression-like behaviors, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, decreased the time in open arms and prolonged immobility. Furthermore, versus the CON group, the expression of HMGB1, TLR4, MyD88, NF-κB, positive cells of Iba-1, IL-1ß and TNF-α were increased but positive cells of GFAP were decreased in CUMS group. However, the detrimental effects were ameliorated by treatment with CUMS+FLU and CUMS+DM. LIMITATIONS: A shortage of this study is that only CUMS model of depression were used, while other depression model were not included. CONCLUSIONS: Du-moxibustion alleviates depression-like behaviors in CUMS mice mainly by reducing neuroinflammation, which offers novel insights into the potential treatment of depression.


Subject(s)
Depression , Disease Models, Animal , HMGB1 Protein , Mice, Inbred C57BL , Moxibustion , Myeloid Differentiation Factor 88 , Neuroinflammatory Diseases , Stress, Psychological , Animals , Mice , Stress, Psychological/complications , Depression/drug therapy , Male , HMGB1 Protein/metabolism , Myeloid Differentiation Factor 88/metabolism , Neuroinflammatory Diseases/drug therapy , Toll-Like Receptor 4/metabolism , Behavior, Animal/drug effects , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-1beta/metabolism
14.
Antimicrob Agents Chemother ; 68(4): e0167823, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38477539

ABSTRACT

Horizontal gene transfer has been demonstrated to be an important driver for the emergency of multidrug-resistant pathogens. Recently, a transferable gene cluster tmexCD1-toprJ1 of the resistance-nodulation-division (RND) superfamily was identified in the plasmids of animal-derived Klebsiella pneumoniae strains, with a higher efflux capacity for various drugs than the Escherichia coli AcrAB-TolC homolog system. In this study, we focused on the differences in the inner membrane pump of these two systems and identified some key residues that contribute to the robust efflux activity of the TMexCD1 system. With the aid of homologous modeling and molecular docking, eight residues from the proximal binding pocket (PBP) and nine from the distal binding pocket (DBP) were selected and subjected to site-directed mutagenesis. Several of them, such as S134, I139, D181, and A290, were shown to be important for substrate binding in the DBP region, and all residues in PBP and DBP showed certain substrate preferences. Apart from the conservative switch loop (L613-623TMexD1) previously identified in the E. coli AcrB (EcAcrB), a relatively unconservative loop (L665-675TMexD1) at the bottom of PBP was proposed as a critical element for the robust activity of TMexD1, due to variations at sites E669, G670, N673, and S674 compared to EcAcrAB, and the significantly altered efflux activity due to their mutations. The conservation and flexibility of these key factors can contribute to the evolution of the RND efflux pumps and thus serve as potential targets for developing inhibitors to block the widespread of the TMexCD1 system.


Subject(s)
Escherichia coli Proteins , Escherichia coli , Animals , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Anti-Bacterial Agents/chemistry , Molecular Docking Simulation , Drug Resistance, Multiple, Bacterial/genetics , Multidrug Resistance-Associated Proteins/genetics , Microbial Sensitivity Tests
15.
Heliyon ; 10(6): e27437, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38501016

ABSTRACT

As the second most common neurodegenerative disease globally, Parkinson's disease (PD) affects millions of people worldwide. In recent years, the scientific publications related to PD biomarker research have exploded, reflecting the growing interest in unraveling the complex pathophysiology of PD. In this study, we aim to use various bibliometric tools to identify key scientific concepts, detect emerging trends, and analyze the global trends and development of PD biomarker research.The research encompasses various stages of biomarker development, including exploration, identification, and multi-modal research. MOVEMENT DISORDERS emerged as the leading journal in terms of publications and citations. Key authors such as Mollenhauer and Salem were identified, while the University of Pennsylvania and USA stood out in collaboration and research output. NEUROSCIENCES emerged as the most important research direction. Key biomarker categories include α-synuclein-related markers, neurotransmitter-related markers, inflammation and immune system-related markers, oxidative stress and mitochondrial function-related markers, and brain imaging-related markers. Furthermore, future trends in PD biomarker research focus on exosomes and plasma biomarkers, miRNA, cerebrospinal fluid biomarkers, machine learning applications, and animal models of PD. These trends contribute to early diagnosis, disease progression monitoring, and understanding the pathological mechanisms of PD.

17.
BMC Psychiatry ; 24(1): 110, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38326834

ABSTRACT

BACKGROUND: Studies examining whether diet sugar intake increases the risk of depression have produced inconsistent results. Therefore, we investigated this relationship, using the US' National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study included 18,439 adults (aged ≥ 20 years) from NHANES (2011-2018). Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9). Covariates, including age, sex, race/ethnicity, poverty-income ratio, education, marital status, hypertension, diabetes mellitus, cardiovascular disease, alcohol intake, smoking status, physical activity, and dietary energy intake, were adjusted in multivariate logistic regression models. Subgroup and threshold saturation effect analyses were performed. RESULTS: After adjusting for potential confounders, we found that a 100 g/day increase in dietary sugar intake correlated with a 28% higher prevalence of depression (odds ratio = 1.28, 95% confidence interval = 1.17-1.40, P < 0.001). CONCLUSION: Dietary sugar intake is positively associated with depression in US adults.


Subject(s)
Depression , Diet , Humans , Adult , Nutrition Surveys , Cross-Sectional Studies , Depression/epidemiology , Depression/etiology , Dietary Sugars/adverse effects
19.
J Affect Disord ; 347: 299-305, 2024 02 15.
Article in English | MEDLINE | ID: mdl-38000467

ABSTRACT

OBJECTIVE: The weight-adjusted-waist index (WWI) serves as an innovative obesity measure, seemingly surpassing body mass index (BMI) and waist circumference (WC) in evaluating lean and fat mass. This study aimed to explore the relationship between WWI and depression in United States (US) adults. METHODS: This population-based study investigated adults with comprehensive WWI and PHQ-9 (9-item Patient Health Questionnaire) data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. WWI was computed by dividing WC by the square root of body weight. Weighted multivariate logistic regression and smoothed curve fitting were employed to examine linear and non-linear associations. Additionally, subgroup analyses and interaction tests were conducted. RESULTS: A total of 34,528 participants were enrolled with a prevalence of depression of 7.61 %. WWI was positively related to depression with the full adjustment [odds ratio (OR) = 1.21, 95 % confidence interval (95 % CI): 1.13-1.29]. After converting WWI to a categorical variable by quartiles (Q1-Q4), compared to Q1 the highest WWI quartile was linked to an obviously increased likelihood of depression (OR = 1.51, 95 % CI: 1.29-1.76). Subgroup analysis revealed the stability of the independent positive relationship between WWI and depression (all P for trend >0.05). CONCLUSION: WWI levels were positively related to an increased likelihood of depression in US adults. Our findings indicated that WWI may serve as a simple anthropometric index to predict depression.


Subject(s)
Obesity , Adult , Humans , United States/epidemiology , Nutrition Surveys , Obesity/epidemiology , Body Mass Index , Waist Circumference , Anthropometry
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