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1.
Alzheimers Dement ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946708

ABSTRACT

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

2.
Nutrients ; 16(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38999822

ABSTRACT

BACKGROUND: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. METHODS: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. RESULTS: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77-0.98]), PUFA (HR: 0.81 [0.73-0.91]), and MUFA (HR: 0.88 [0.77-0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17-1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13-1.50]), and MUFA (HR: 1.28 [1.13-1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. CONCLUSIONS: Meal timing influences the association of UFAs with all-cause and CVD-related mortality.


Subject(s)
Cardiovascular Diseases , Fatty Acids, Unsaturated , Meals , Humans , Male , Female , Prospective Studies , Cardiovascular Diseases/mortality , Middle Aged , Adult , Fatty Acids, Unsaturated/administration & dosage , Follow-Up Studies , Aged , Fatty Acids, Monounsaturated/administration & dosage , Proportional Hazards Models , Time Factors , Diet , Cause of Death , Young Adult
3.
BMC Oral Health ; 24(1): 773, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987730

ABSTRACT

OBJECTIVE: Resveratrol (Res) is a natural phytoestrogen with antitumor activity. This study sought to investigate the role of Res in ferroptosis in oral squamous cell carcinoma (OSCC). METHODS: Normal human oral keratinocyte (HOK)/oral OSCC (CAL-27/SCC-9) cell lines were treated with different doses of Res. Res toxicity was determined by MTT assay, with half maximal inhibitory concentration values of Res on CAL-27 and SCC-9 cells calculated. Cell viability/colony formation efficiency/migration/invasion/cycle were assessed by CCK-8/colony formation assay/transwell assay/flow cytometry. The expression of p53 protein in the nucleus and cytoplasm, glutathione peroxidase 4 (GPX4) expression, and SLC7A11 messenger RNA (mRNA) and protein expression levels were determined by Western blot and RT-qPCR. Fe2+ content, reactive oxygen species (ROS) level, reduced glutathione (GSH), and lactate dehydrogenase (LDH) release were assessed. RESULTS: Medium- to low-dose Res had no toxic effect on HOK cells, while high-dose Res markedly reduced HOK cell viability. Res significantly suppressed the viability of OSCC cells (CAL-27 and SCC-9). Res inhibited OSCC cell colony formation/migration/invasion, and induced G1 phase arrest. Res caused the translocation of p53 protein to the nucleus, obviously increased Fe2+ content, ROS level and LDH release, decreased GSH content and GPX4 protein expression, and induced ferroptosis. Down-regulation of p53 partially reversed the inhibitory effects of Res on CAL-27 cell malignant behaviors. Res inhibited SLC7A11 transcription by promoting p53 entry into the nucleus. SLC7A11 overexpression negated the the regulatory effects of p53 knockout on the role of Res in OSCC cell malignant behaviors and ferroptosis. CONCLUSION: Res accelerated ferroptosis and inhibited malignant behaviors in OSCC cells by regulating p53/SLC7A11.


Subject(s)
Amino Acid Transport System y+ , Carcinoma, Squamous Cell , Ferroptosis , Mouth Neoplasms , Resveratrol , Tumor Suppressor Protein p53 , Humans , Resveratrol/pharmacology , Resveratrol/therapeutic use , Ferroptosis/drug effects , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/drug effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Mouth Neoplasms/drug therapy , Mouth Neoplasms/metabolism , Amino Acid Transport System y+/metabolism , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Cell Survival/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism
4.
BMC Geriatr ; 24(1): 492, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840066

ABSTRACT

BACKGROUND: There is limited understanding regarding prospective associations of insomnia symptoms and trajectories with functional disability. We aimed to investigate the associations of insomnia symptoms and trajectories with functional disability. METHOD: A total of 13 197 participants were eligible from the Health and Retirement Study. Insomnia symptoms included non-restorative sleep, difficulty initiating sleep, early morning awakening, and difficulty maintaining sleep. We also identified four distinct trajectories of insomnia symptoms: low, decreasing, increasing, and high insomnia symptoms. Functional status was assessed through activities of daily living (ADL) and instrumental activities of daily living (IADL). RESULTS: Participants experiencing one (HR, 1.21; 95% CI, 1.13-1.29), two (HR, 1.43; 95% CI, 1.29-1.57), or three to four (HR, 1.41; 95% CI, 1.25-1.60) insomnia symptoms had a higher risk of ADL disability than asymptomatic respondents. Similarly, participants with one or more insomnia symptoms had a higher risk of IADL disability. Furthermore, using the trajectory with low insomnia symptoms as the reference, decreasing insomnia symptoms (HR, 1.22; 95% CI, 1.12-1.34), increasing insomnia symptoms (HR, 1.21; 95% CI, 1.05-1.41), and high insomnia symptoms (HR, 1.36; 95% CI, 1.18-1.56) were all associated with an increased risk of ADL disability. CONCLUSION: Both a single measurement and dynamic trajectory of insomnia symptoms are associated with the onset of ADL disability. Increased awareness and management of insomnia symptoms may contribute to the prevention of functional disability occurrence.


Subject(s)
Activities of Daily Living , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/diagnosis , Female , Male , Prospective Studies , Aged , Middle Aged , Disabled Persons , Cohort Studies , Disability Evaluation , Risk Factors
5.
Mol Pharm ; 21(7): 3395-3406, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38836777

ABSTRACT

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.


Subject(s)
Drug Liberation , Methylcellulose , Sodium Hydroxide , Solubility , Sodium Hydroxide/chemistry , Methylcellulose/chemistry , Methylcellulose/analogs & derivatives , Polymers/chemistry , Drug Carriers/chemistry , Chemistry, Pharmaceutical/methods , Drug Compounding/methods , Pyrrolidines/chemistry
6.
Int J Pharm ; 660: 124383, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38925240

ABSTRACT

The purpose of the study is introduce a two-phase flow model to simulate water penetration into pharmaceutical tablets. This model was built by integrating Darcy's law with the continuity principle, on the premise that water penetration was driven by capillary actions. Notably, this model concerned both the ingress of water (wetting phase) and simultaneous displacement of air (non-wetting phase). Due to the interference of the two fluids, the relative permeability and capillary pressure vary during water penetration. Evolution of these parameters was incorporated in the model. Calibration of the model by water penetration experiments of the microcrystalline cellulose (MCC) tablet yielded an average pore radius of 42 nm. This derived result was corroborated by FIB-SEM analysis revealing the presence of extensive microporosity within MCC particles with an average radius of ∼30 nm. Further validation was achieved through close resemblance between the simulated and experimental water penetration profiles of MCC tablets possessing different porosities. Overall, this study underscored the advantage of the two-phase flow model over single-phase flow models, by capturing the dependence of permeability and capillary pressure on water saturation. Therefore it holds promise for an enhanced description of water penetration into tablets.


Subject(s)
Cellulose , Permeability , Tablets , Water , Cellulose/chemistry , Water/chemistry , Porosity , Models, Theoretical , Excipients/chemistry
7.
Int J Obes (Lond) ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926462

ABSTRACT

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

8.
Anal Chem ; 96(26): 10586-10593, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38887018

ABSTRACT

This study investigated the added value of combining both near-infrared (NIR) and Raman spectroscopy into a single NIRaman Combi Fiber Probe for in-line blend potency determination in the feed frame of a rotary tablet press. A five-component platform formulation was used, containing acetylsalicylic acid as the Active Pharmaceutical Ingredient (API). Calibration models for the determination of 1 and 5%w/w label claim tablets were developed using NIR and Raman spectra of powder blends ranging from 0.75 to 1.25%w/w and 3.75 to 6.25%w/w API, respectively. Step-change experiments with deliberate 10% deviation steps from the label claims were performed, from which the collected spectra were used for model validation. For model development and validation, low-level data fusion was explored through concatenation of preprocessed NIR and Raman spectra. Mid-level data fusion was also evaluated, based on extracted features of the preprocessed data. Herewith, score vectors were extracted by transforming preprocessed spectra through Principal Component Analysis, followed by critical feature selection through Elastic Net Regression. Partial Least Squares regression was applied to regress singular, low-level or mid-level fused data versus blend potency. It could be concluded that irrespective of the data fusion technique, an increase in Step-Change Sensitivity (SCS) and decrease in Root Mean Squared Error (RMSE) was observed when predicting the 5%w/w step-change experiment. For the prediction of the 1%w/w step-change experiment, no added benefit with regard to SCS and RMSE was observed due to the addition of the noisy NIR spectra.


Subject(s)
Aspirin , Spectroscopy, Near-Infrared , Spectrum Analysis, Raman , Tablets , Spectrum Analysis, Raman/methods , Tablets/chemistry , Spectroscopy, Near-Infrared/methods , Aspirin/analysis , Principal Component Analysis , Calibration
9.
J Integr Med ; 22(3): 223-234, 2024 May.
Article in English | MEDLINE | ID: mdl-38714484

ABSTRACT

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.


Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Randomized Controlled Trials as Topic , Humans , Drugs, Chinese Herbal/therapeutic use , Epidemiologic Studies , Treatment Outcome
10.
Anal Methods ; 16(21): 3392-3412, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38752456

ABSTRACT

Cocculus orbiculatus (L.) DC. (C. orbiculatus) is a medicinal herb valued for its dried roots with anti-inflammatory, analgesic, diuretic, and other therapeutic properties. Despite its traditional applications, chemical investigations into C. orbiculatus remain limited, focusing predominantly on alkaloids and flavonoids. Furthermore, the therapeutic use of C. orbiculatus predominantly focuses on the roots, leaving the stems, a significant portion of the plant, underutilized. This study employed ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) with in-house and online databases for comprehensive identification of components in various plant parts. Subsequently, untargeted metabolomics was employed to analyze differences in components across different harvest periods and plant sections of C. orbiculatus, aiming to screen for distinct components in different parts of the plant. Finally, metabolomic analysis of the roots and stems, which contribute significantly to the plant's weight, was conducted using chemometrics, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), and heatmaps. A total of 113 components, including alkaloids, flavonoids, and organic acids, were annotated across the root, stem, leaf, flower, and fruit, along with numerous previously unreported compounds. Metabolomic analyses revealed substantial differences in components between the root and stem compared to the leaf, flower, and fruit during the same harvest period. PLS-DA and OPLS-DA annotated 10 differentiating components (VIP > 1.5, P < 0.05, FC > 2 or FC < 0.67), with 5 unique to the root and stem, exhibiting lower mass spectrometric responses. This study provided the first characterization of 113 chemical constituents in different parts of C. orbiculatus, laying the groundwork for pharmacological research and advocating for the enhanced utilization of its stem.


Subject(s)
Metabolomics , Plant Roots , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Metabolomics/methods , Plant Roots/chemistry , Flavonoids/analysis , Alkaloids/analysis , Alkaloids/chemistry , Plant Stems/chemistry , Plant Extracts/chemistry , Principal Component Analysis
11.
Biochem Biophys Res Commun ; 716: 150038, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38704891

ABSTRACT

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.


Subject(s)
Glycosides , Hyperuricemia , NLR Family, Pyrin Domain-Containing 3 Protein , Pyrans , Uric Acid , Animals , Hyperuricemia/drug therapy , Hyperuricemia/metabolism , Uric Acid/blood , Male , Glycosides/pharmacology , Glycosides/therapeutic use , Pyrans/pharmacology , Pyrans/therapeutic use , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , NF-kappa B/metabolism , Mice, Inbred C57BL
12.
Diabetes Obes Metab ; 26(8): 3238-3247, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38783824

ABSTRACT

AIMS: To investigate the associations of conicity index (C-index) and relative fat mass (RFM) with incident type 2 diabetes mellitus (T2DM) among adults in China. MATERIALS AND METHODS: A total of 10 813 participants aged over 18 years in Shenzhen Longhua district were enrolled in a follow-up study conducted from 2018 to 2022. The participants were categorized based on quartiles (Q) of C-index and RFM. The Cox proportional hazards model was performed to examine the relationships between C-index, RFM and the risk of T2DM. RESULTS: After adjusting for potential confounding factors, including age, sex, occupation, marital status, education level, smoking status, alcohol consumption, physical exercise, hypertension status, fasting blood glucose (FBG) and total cholesterol (TC), both C-index and RFM showed positive and independent associations with risk of T2DM. The multivariable-adjusted hazard ratios (95% confidence intervals) for T2DM risk in participants in C-index Q3 and Q4 compared with those in C-index Q1 were 1.50 (1.12, 2.02) and 1.73 (1.29, 2.30), and 1.94 (1.44, 2.63), 3.18 (1.79, 5.64), 4.91 (2.68, 9.00) for participants in RFM Q2, Q3 and Q4 compared with RFM Q1. These differences were statistically significant (all p < 0.05). CONCLUSION: C-index and RFM are strongly associated with new-onset T2DM and could be used to identify the risk of diabetes in large-scale epidemiological studies.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/epidemiology , Female , Male , China/epidemiology , Middle Aged , Adult , Follow-Up Studies , Risk Factors , Anthropometry , Aged , Incidence , Adiposity , Body Mass Index , East Asian People
13.
BMC Psychiatry ; 24(1): 266, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594684

ABSTRACT

BACKGROUND: Pregnant women who have undergone pregnancy loss often display both posttraumatic stress (PTS) and posttraumatic growth (PTG). However, the precise relationship and structure of symptomatic levels of PTS and PTG have not been well understood. This study aimed to assess the associations between PTS and PTG symptoms in women during subsequent pregnancies following a previous pregnancy loss. METHODS: A total of 406 pregnant women with a history of pregnancy loss were included in this study. The Impact of Events Scale-6 (IES-6) and the Posttraumatic Growth Inventory Short Form (PTGI-SF) were used to assess symptoms of PTS and PTG, respectively. The Graphical Gaussian Model was employed to estimate the network model. Central symptoms and bridge symptoms were identified based on "expected influence" and "bridge expected influence" indices, respectively. The stability and accuracy of the network were examined using the case-dropping procedure and nonparametric bootstrapped procedure. RESULTS: The network analysis identified PTG3 ("Ability to do better things") as the most central symptom, followed by PTS3 ("Avoidance of thoughts") and PTG6 ("New path for life") in the sample. Additionally, PTS3 ("Avoidance of thoughts") and PTG9 ("Perception of greater personal strength") were bridge symptoms linking PTS and PTG clusters. The network structure was robust in stability and accuracy tests. CONCLUSIONS: Interventions targeting the central symptoms identified, along with key bridge symptoms, have the potential to alleviate the severity of PTS experienced by women with a history of pregnancy loss and promote their personal growth.


Subject(s)
Abortion, Spontaneous , Posttraumatic Growth, Psychological , Stress Disorders, Post-Traumatic , Pregnancy , Humans , Female , Adaptation, Psychological , Stress Disorders, Post-Traumatic/diagnosis
14.
J Dermatolog Treat ; 35(1): 2343072, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38626923

ABSTRACT

BACKGROUND: Systematic reviews (SRs) could offer the best evidence supporting interventions, but methodological flaws limit their trustworthiness in decision-making. This cross-sectional study appraised the methodological quality of SRs on atopic dermatitis (AD) treatments. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and Cochrane Database for SRs on AD treatments published in 2019-2022. We extracted SRs' bibliographical data and appraised SRs' methodological quality with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We explored associations between methodological quality and bibliographical characteristics. RESULTS: Among the 52 appraised SRs, only one (1.9%) had high methodological quality, while 45 (86.5%) critically low. For critical domains, only five (9.6%) employed comprehensive search strategy, seven (13.5%) provided list of excluded studies, 17 (32.7%) considered risk of bias in primary studies, 21 (40.4%) contained registered protocol, and 24 (46.2%) investigated publication bias. Cochrane reviews, SR updates, SRs with European corresponding authors, and SRs funded by European institutions had better overall quality. Impact factor and author number positively associated with overall quality. CONCLUSIONS: Methodological quality of SRs on AD treatments is unsatisfactory. Future reviewers should improve the above critical methodological aspects. Resources should be devolved into upscaling evidence synthesis infrastructure and improving critical appraisal skills of evidence users.


Subject(s)
Dermatitis, Atopic , Humans , Cross-Sectional Studies , Dermatitis, Atopic/drug therapy , Systematic Reviews as Topic , Research Design
15.
J Agric Food Chem ; 72(17): 9828-9841, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38639269

ABSTRACT

Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10-7 and (6.63 ± 2.31) × 10-7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.


Subject(s)
Antihypertensive Agents , Humans , Caco-2 Cells , Biological Transport , Antihypertensive Agents/chemistry , Antihypertensive Agents/metabolism , 1,2-Dipalmitoylphosphatidylcholine/chemistry , 1,2-Dipalmitoylphosphatidylcholine/metabolism , Diffusion , Zonula Occludens-1 Protein/metabolism , Zonula Occludens-1 Protein/genetics , Oligopeptides/chemistry , Oligopeptides/metabolism , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism
16.
Pharm Res ; 41(5): 947-958, 2024 May.
Article in English | MEDLINE | ID: mdl-38589647

ABSTRACT

PURPOSE: We aim to present a refined thin-film model describing the drug particle dissolution considering radial diffusion in spherical boundary layer, and to demonstrate the ability of the model to describe the dissolution behavior of bulk drug powders. METHODS: The dissolution model introduced in this study was refined from a radial diffusion-based model previously published by our laboratory (So et al. in Pharm Res. 39:907-17, 2022). The refined model was created to simulate the dissolution of bulk powders, and to account for the evolution of particle size and diffusion layer thickness during dissolution. In vitro dissolution testing, using fractionated hydrochlorothiazide powders, was employed to assess the performance of the model. RESULTS: Overall, there was a good agreement between the experimental dissolution data and the predicted dissolution profiles using the proposed model across all size fractions of hydrochlorothiazide. The model over-predicted the dissolution rate when the particles became smaller. Notably, the classic Nernst-Brunner formalism led to an under-estimation of the dissolution rate. Additionally, calculation based on the equivalent particle size derived from the specific surface area substantially over-predicted the dissolution rate. CONCLUSION: The study demonstrated the potential of the radial diffusion-based model to describe dissolution of drug powders. In contrast, the classic Nernst-Brunner equation could under-estimate drug dissolution rate, largely due to the underlying assumption of translational diffusion. Moreover, the study indicated that not all surfaces on a drug particle contribute to dissolution. Therefore, relying on the experimentally-determined specific surface area for predicting drug dissolution is not advisable.


Subject(s)
Drug Liberation , Hydrochlorothiazide , Particle Size , Powders , Solubility , Powders/chemistry , Diffusion , Hydrochlorothiazide/chemistry , Chemistry, Pharmaceutical/methods , Models, Chemical , Computer Simulation
17.
Eur Heart J ; 45(24): 2145-2154, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38626306

ABSTRACT

BACKGROUND AND AIMS: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.


Subject(s)
Body Mass Index , Mendelian Randomization Analysis , Waist Circumference , Humans , Female , Male , Aged, 80 and over , China/epidemiology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/genetics , Polymorphism, Single Nucleotide , Obesity/genetics , Obesity/mortality , Cause of Death , Risk Factors , Mortality
18.
Front Psychiatry ; 15: 1326894, 2024.
Article in English | MEDLINE | ID: mdl-38525260

ABSTRACT

Background: Increasing evidence suggests that pregnancy loss can lead to negative emotional outcomes, such as anxiety and depression, for women. However, limited knowledge exists regarding the long-term risk of mental disorders among individuals who have experienced pregnancy loss. Objective: To investigate the associations between pregnancy loss and the risk of common mental disorders. Methods: In the UK Biobank, a total of 218,990 women without any mental disorder at baseline were enrolled between 2006 and 2010 and followed until October 2022. Information on the history of pregnancy loss was obtained through self-reported questionnaires at baseline. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between pregnancy loss and common mental disorders. Results: During a median follow-up time of 13.36 years, there were 26,930 incident cases of common mental disorders. Incidence rates of common mental disorders were elevated among women with a history of stillbirth (HR 1.15, 95% CI: 1.07-1.23), miscarriage (HR 1.06, 95% CI: 1.02-1.10), or pregnancy termination (HR 1.21, 95% CI: 1.17-1.25) compared to those without such experiences. Furthermore, the risk of common mental disorders significantly increased in women with two or more miscarriages (HR 1.14, 95% CI: 1.08-1.19) or two or more pregnancy terminations (HR 1.39, 95% CI: 1.30-1.48). Conclusions: Pregnancy loss is associated with an increased risk of common mental disorders in women later in life. These findings may contribute to the enhancement of long-term monitoring and prevention of common mental disorders for women with such a history.

19.
Ecotoxicol Environ Saf ; 274: 116176, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38479309

ABSTRACT

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.


Subject(s)
Air Pollutants , Air Pollution , Respiratory Tract Diseases , Humans , Air Pollutants/adverse effects , Air Pollutants/analysis , Particulate Matter/toxicity , Particulate Matter/analysis , Prospective Studies , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Respiratory Tract Diseases/epidemiology , Nitrogen Dioxide
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124172, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38513316

ABSTRACT

Hesperidin (HE), a significant flavonoid polyphenolic compound present in citrus plants, exhibits diverse pharmacological effects. Considering the crucial involvement of biological membranes and transporter proteins in the transportation and biological processes of HE, it becomes essential to comprehend the potential mechanisms through which HE interacts with membranes and transporter proteins. In order to simulate the process of active molecule transport, a cell membrane model consisting of 1,2-dipalmitoyl-n-glycero-3-phosphatidylcholine (DPPC) and a transporter protein model of bovine serum albumin (BSA) were employed for investigation. The present study aimed to investigate the mechanism of action of hesperidin (HE) in DPPC and BSA using fluorescence quenching, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The localization and interaction of HE within liposomes were also elucidated. Furthermore, the binding of BSA and HE was analyzed through UV/Vis absorption spectroscopy, fluorescence spectroscopy, infrared spectroscopy, and computational biology techniques. Computational biology analysis revealed that the binding between HE and BSA primarily occurred via hydrogen bonding and hydrophobic interactions. This study aimed to investigate the role and mechanism of HE in the DPPC cell membrane model and the BSA transporter protein model, thereby offering novel insights into the action of HE in DPPC and BSA.


Subject(s)
Hesperidin , Serum Albumin, Bovine/chemistry , Liposomes/chemistry , Flavonoids/chemistry , 1,2-Dipalmitoylphosphatidylcholine , Spectroscopy, Fourier Transform Infrared , Spectrometry, Fluorescence
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