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1.
Chem Biodivers ; : e202401220, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869421

ABSTRACT

Anoectochilus roxburghii is a well-known and valuable traditional Chinese herb due to various medicinal and functional benefits. In-depth investigation is necessary to discover active ingredients and expand its application. In this study, four new compounds (1-4) along with ten known compounds (5-14) were isolated from the ethanol extract ofA.roxburghii. Their structures were elucidated by spectroscopic data interpretation. The isolates were screened for their inhibitory activities on the production of NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among them, compounds 5, 6, 9, 10, 12, 13 and 14exhibited significant anti-inflammatory activity through inhibiting the release of NO.

2.
Osteoporos Int ; 34(1): 101-109, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36241848

ABSTRACT

This population-based longitudinal follow-up study showed a protective effect of tea consumption against osteoporosis, particularly among women and middle-aged people. High tea consumption was also associated with a reduced risk of hip fracture. INTRODUCTION: To investigate the association of tea consumption with the risks of osteoporosis and hip fracture. METHODS: This study used the Keelung Community-based Integrated Screening database and Taiwan's National Health Insurance Research Database. A total of 42,742 subjects aged 45 to 74 years were enrolled. Each was classified as no tea consumption, low tea consumption, and high tea consumption, according to the results of an eating habits questionnaire. The diagnosis of osteoporosis and hip fracture was based on BMD measured by dual-energy X-ray absorptiometry and the X-ray findings. The median follow-up time was 8.5 years. RESULTS: As compared with the no tea consumption group, the osteoporosis HRs for the low tea consumption and high tea consumption groups were 0.88 (95% confidence interval (CI) 0.80-0.96) and 0.87 (95% CI 0.80-0.94), respectively. Among those participants aged 59 or below, the osteoporosis HRs for low tea consumption and high tea consumption (vs. no tea consumption) were 0.85 (95% CI 0.74-0.96) and 0.79 (95% CI 0.69-0.90). The HRs of hip fracture for the low tea consumption and high tea consumption groups (vs. no tea consumption) were 0.85 (95% CI 0.67-1.08) and 0.69 (95% CI 0.55-0.86), respectively. CONCLUSION: Tea consumption was linked to a lower risk of osteoporosis, particularly among women and middle-aged people. High tea consumption was also associated with a reduced risk of hip fracture.


Subject(s)
Hip Fractures , Osteoporosis , Middle Aged , Female , Humans , Follow-Up Studies , Osteoporosis/epidemiology , Osteoporosis/etiology , Hip Fractures/epidemiology , Hip Fractures/etiology , Hip Fractures/prevention & control , Absorptiometry, Photon/methods , Risk , Bone Density , Risk Factors
3.
Sleep Breath ; 27(5): 2069-2076, 2023 10.
Article in English | MEDLINE | ID: mdl-36856923

ABSTRACT

PURPOSE: Ferroptosis is reported to be involved in the chronic intermittent hypoxia (CIH)-related liver damage in vivo. Nuclear factor E2-related factor 2 (Nrf2) has an essential role in the regulation of ferroptosis. This study tested the hypothesis that intermittent hypoxia (IH) could lead to hepatocyte ferroptosis in vitro and the function of Nrf2 in IH-induced hepatocyte ferroptosis. METHODS: BRL-3A cells (rat liver cells) were exposed to normoxia or IH. The protocol of IH consisted of 32 cycles of 60-min hypoxic exposure with 30-min reoxygenation phase (nadir of 1% oxygen to peak of 20% oxygen). Ferroptosis was evaluated by cell viability, iron concentration, lipid reactive oxygen species (ROS), protein content of ferritin heavy chain (FTH1), and glutathione peroxidase 4 (GPX4). Both ferrostatin-1 (a ferroptosis inhibitor) and Nrf2 interfering RNA were applied to treat BRL-3A cells, respectively. RESULTS: IH exposure induced ferroptosis in BRL-3A cells with decreased cell viability and increased total iron content and lipid ROS levels. The protein contents of GPX4 and FTH1 in IH group were markedly lower than that in normoxic control. Ferroptosis inhibitor ferrostatin-1 alleviated IH-induced ferroptosis in BRL-3A cells. IH treatment enhanced expression of Nrf2, and Nrf2 knockdown augmented IH-induced ferroptosis in BRL-3A cells. CONCLUSIONS: The results revealed that Nrf2 played a protective role during IH-induced ferroptosis in BRL-3A cells. The finding provides a therapeutic target for obstructive sleep apnea-related liver injury.


Subject(s)
Ferroptosis , Animals , Rats , Hypoxia/metabolism , Iron/metabolism , Lipids , Liver/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxygen/metabolism , Reactive Oxygen Species/metabolism
4.
J Cell Mol Med ; 26(3): 750-763, 2022 02.
Article in English | MEDLINE | ID: mdl-34935260

ABSTRACT

Islet ß cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell-derived factor-1 (SDF-1) in the dedifferentiation of islet ß cells. It was noted that the number of dedifferentiated islet ß cells and the expression of SDF-1 in pancreatic tissues significantly increased with diabetes. In islet ß cell experiments, inhibition of SDF-1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF-1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF-1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF-1 activity. SDF-1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet ß cells. This suggests that SDF-1 may be a novel target in the treatment of diabetes.


Subject(s)
Hyperglycemia , Insulin-Secreting Cells , Islets of Langerhans , Chemokine CXCL12/metabolism , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Humans , Hyperglycemia/metabolism , Insulin-Secreting Cells/metabolism , Islets of Langerhans/metabolism , Pancreas/metabolism , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Signal Transduction
5.
Scand J Gastroenterol ; 56(3): 312-320, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33535004

ABSTRACT

OBJECTIVE: Obesity and sarcopenia are known to be closely related to nonalcoholic fatty liver disease (NAFLD). We attempted to explore the combined influence of fat and muscle tissue on NAFLD by using visceral fat area to appendicular muscle mass ratio (VAR) as a novel parameter. MATERIAL AND METHODS: In this cross-sectional study, a total of 3255 adults (1399 men and 1856 women) coming for a health examination were enrolled. NAFLD was diagnosed using ultrasound and VAR was measured by bioelectrical impedance analyzer. RESULTS: The prevalence of NAFLD was 46.5% in men and 26.6% in women. VAR differed significantly between subjects with and without NAFLD (4.27 vs. 3.26 in men, 7.89 vs. 5.01 in women, respectively, p < .001). Logistic regression analysis determined VAR as a risk factor for NAFLD, and the multivariable-adjusted odds ratios in the highest VAR quartile was 9.57 (95%CI: 5.98-15.30) for men and 12.37 (95%CI: 6.37-24.05) for women. From the receiver operating characteristic analysis, the area under the curve was 0.767 and 0.834, with the suitable cut-off VAR value of 3.469 and 6.357 for men and women, respectively. To control the influence of obesity, all subjects were stratified according to their BMI. For each BMI group, individuals with VAR above the cut-off value had significant higher prevalence and risk of NAFLD, with odds ratios ranging from 1.76 to 4.75. CONCLUSIONS: Increased VAR is strongly associated with higher risk of NAFLD in both sexes independent of obesity and can serve as a screening reference for NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Adult , Body Mass Index , Cross-Sectional Studies , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Male , Muscles , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity/complications , Obesity/epidemiology , Risk Factors
6.
Bioorg Chem ; 111: 104843, 2021 06.
Article in English | MEDLINE | ID: mdl-33845383

ABSTRACT

Gynostemma pentaphyllum (Thunb.) Makino has a long history as food and diary supplement in China. At present, there are some products for hyperlipidemia in the market, including G. pentaphyllum tea, healthy wine and healthy food. In order to discover proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fourteen new triterpenoid saponins named gypenoside LXXXVIII-CI (1-14) along with six known compounds (15-20) were isolated from G. pentaphyllum. Their structures were elucidated by means of various spectroscopic techniques. Eight isolates were evaluated the inhibitory effect on PCSK9 in HepG2 cells. The results showed that three dammarane-type glycosides (2, 3, 15) remarkably reduced PCSK9 expression at 10 µM concentration. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule PCSK9 inhibitors and facilitate their utilization as functional food ingredients.


Subject(s)
Glycosides/pharmacology , Gynostemma/chemistry , Lipids/antagonists & inhibitors , PCSK9 Inhibitors , Triterpenes/pharmacology , Dose-Response Relationship, Drug , Glycosides/chemistry , Glycosides/isolation & purification , Hep G2 Cells , Humans , Molecular Structure , Proprotein Convertase 9/genetics , Proprotein Convertase 9/metabolism , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/isolation & purification , Tumor Cells, Cultured , Dammaranes
7.
Bioorg Chem ; 116: 105357, 2021 11.
Article in English | MEDLINE | ID: mdl-34562675

ABSTRACT

Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae family) is a perennial creeping plant with a common Chinese name of "south ginseng". To date, more than 250 individual saponins with dammarane-type skeleton have been isolated from G. pentaphyllum. The purpose of this study was the isolation and structural characterization of novel, minor gypenosides from G. pentaphyllum and evaluation of their Sirt1 agonist activity. Individual saponins from G. pentaphyllum were isolated and purified by a variety of chromatography techniques, and their structures were elucidated by means of various spectroscopic analysis and comparision with the reported data. Sirt1 enzyme activity detection kit was used to preliminarily evaluate the Sirt1 agonist activity of thirty three individual saponins purified from G. pentaphyllum. Fourteen new triterpenoid saponins named gypenoside CII-CXV (1-14) along with twenty six known compounds (15-40) were isolated from G. pentaphyllum. Thirty three of all the isolates were screened for Sirt1 agonist activity, and the results showed that three dammarane-type saponins (2, 18, 37) and one cucurbitane-type saponin 33 exhibited satisfactory Sirt1 agonist activity. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule Sirt1 agonist and facilitate their utilization as "south ginseng".


Subject(s)
Gynostemma/chemistry , Saponins/pharmacology , Sirtuin 1/metabolism , Triterpenes/pharmacology , Dose-Response Relationship, Drug , Humans , Molecular Structure , Saponins/chemistry , Saponins/isolation & purification , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/isolation & purification , Dammaranes
8.
BMC Infect Dis ; 20(1): 517, 2020 Jul 16.
Article in English | MEDLINE | ID: mdl-32677909

ABSTRACT

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of major international concern. Real-time RT-PCR assays are recommended for diagnosis of COVID-19. Here we report a rare case of COVID-19 with multiple negative results for PCR assays outside Wuhan, China. CASE PRESENTATION: A 32-year old male was admitted to our hospital because of 6 days of unexplained fever on January 29, 2020. He had come from Wuhan city 10 days before admission. Five days before admission, no abnormality was noted in laboratory test, chest radiography, and nasopharyngeal swab test for the SARS-CoV-2 nucleic acid. The patient was treated with ibuprofen for alleviating fever. On admission, chest computed tomography showed multiple ground-glass opacities in right lower lung field. COVID-19 was suspected. Three times of nasopharyngeal swab specimens were collected after admission. However, none of the specimens were positive. The patient was confirmed with COVID-19 after fifth SARS-CoV-2 nucleic acid test. He was treated with lopinavir/ritonavir, recombinant human interferon alfa-2b inhalation, methylprednisolone. After 18 days of treatment, he was discharged with improved symptoms, lung lesions and negative results of nasopharyngeal swab. CONCLUSION: This case reminds clinician that a patient with high clinical suspicion of COVID-19 but multiple negative RT-PCR result should not be taken out of isolation. A combination of patient's exposure history, clinical manifestations, laboratory tests, and typical imaging findings plays a vital role in making preliminary diagnosis and guide early isolation and treatment. Repeat swab tests are helpful in diagnosis for this kind of patients.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Negative Results , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Adult , Betacoronavirus/genetics , COVID-19 , China/epidemiology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Fever/etiology , Fever/virology , Hospitalization , Humans , Male , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Quarantine , Radiography , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and Specificity , Tomography, X-Ray Computed , Uncertainty
9.
J Am Chem Soc ; 141(21): 8489-8502, 2019 05 29.
Article in English | MEDLINE | ID: mdl-31067051

ABSTRACT

Recent research on the structure and mechanism of DNA polymerases has continued to generate fundamentally important features, including a noncanonical pathway involving "prebinding" of metal-bound dNTP (MdNTP) in the absence of DNA. While this noncanonical mechanism was shown to be a possible subset for African swine fever DNA polymerase X (Pol X) and human Pol λ, it remains unknown whether it could be the primary pathway for a DNA polymerase. Pol µ is a unique member of the X-family with multiple functions and with unusual Mn2+ preference. Here we report that Pol µ not only prebinds MdNTP in a catalytically active conformation but also exerts a Mn2+ over Mg2+ preference at this early stage of catalysis, for various functions: incorporation of dNTP into a single nucleotide gapped DNA, incorporation of rNTP in the nonhomologous end joining (NHEJ) repair, incorporation of dNTP to an ssDNA, and incorporation of an 8-oxo-dGTP opposite template dA (mismatched) or dC (matched). The structural basis of this noncanonical mechanism and Mn2+ over Mg2+ preference in these functions was analyzed by solving 19 structures of prebinding binary complexes, precatalytic ternary complexes, and product complexes. The results suggest that the noncanonical pathway is functionally relevant for the multiple functions of Pol µ. Overall, this work provides the structural and mechanistic basis for the long-standing puzzle in the Mn2+ preference of Pol µ and expands the landscape of the possible mechanisms of DNA polymerases to include both mechanistic pathways.


Subject(s)
DNA-Directed DNA Polymerase/metabolism , Manganese/metabolism , DNA-Directed DNA Polymerase/chemistry , DNA-Directed DNA Polymerase/isolation & purification , Humans , Manganese/chemistry , Models, Molecular
10.
Anal Chem ; 90(3): 2018-2022, 2018 02 06.
Article in English | MEDLINE | ID: mdl-29275628

ABSTRACT

Raman scattering and fluorescence spectroscopy permeate analytic science and are featured in the plasmon-enhanced spectroscopy (PES) family. However, the modest enhancement of plasmon-enhanced fluorescence (PEF) significantly limits the sensitivity in surface analysis and material characterization. Herein, we report a Ag nanoantenna platform, which simultaneously fulfills very strong emission (an optimum average enhancement of 105-fold) and an ultrafast emission rate (∼280-fold) in PES. For applications in surface science, this platform has been examined with a diverse array of fluorophores. Meanwhile, we utilized a finite-element method (FEM) and time-dependent density functional theory (TD-DFT) to comprehensively investigate the mechanism of largely enhanced radiative decay. PES with a shell-isolated Ag nanoantenna will open a wealth of advanced scenarios for ultrasensitive surface analysis.

11.
Eur Arch Otorhinolaryngol ; 275(2): 587-594, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29224042

ABSTRACT

INTRODUCTION: Obstructive sleep apnea (OSA) has been suggested to be a potential contributing factor for nonalcoholic fatty liver disease (NAFLD). Studies on the association between continuous positive airway pressure (CPAP) and NAFLD in OSA patients are limited and controversial. OBJECTIVES: The aim of this study was to assess the relationship between OSA and NAFLD and the effect of CPAP therapy on serum aminotransferase levels in OSA patients. METHODS: A total of 160 consecutive patients who underwent standard polysomnography were enrolled. Blood samples were obtained in the morning after sleep for biological profile measurements. Non-invasive ultrasound techniques were used to assess liver steatosis and fibrosis. Within the OSA group, serum aminotransferases were detected before and after CPAP treatment. RESULTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, and liver steatosis score increased significantly with an increase in OSA severity. Stepwise multiple regression with liver steatosis score, ALT, AST as dependent variable, respectively, apnea-hypopnea index (ß = 0.447, p = 0.020; ß = 0.266, p = 0.001; ß = 0.351, p = 0.020, respectively) significantly predicted the liver steatosis score, ALT, AST after adjustment for confounders. After 3 months of CPAP treatment, there was a significant decrease in both ALT (54.20 ± 24.34 vs. 46.52 ± 24.95, p = 0.000) and AST (31.82 ± 8.91 vs. 29.00 ± 8.34, p = 0.039). CONCLUSIONS: OSA severity was independently associated with liver steatosis and elevation of serum aminotransferases. 3 months of CPAP therapy were associated with a statistically significant improvement on liver injury in OSA patients.


Subject(s)
Continuous Positive Airway Pressure , Non-alcoholic Fatty Liver Disease/etiology , Sleep Apnea, Obstructive/blood , Transaminases/blood , Adolescent , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Fatty Liver/diagnostic imaging , Fatty Liver/etiology , Female , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Polysomnography , Risk Factors , Sleep Apnea, Obstructive/complications , Ultrasonography , Young Adult , gamma-Glutamyltransferase/blood
12.
Angew Chem Int Ed Engl ; 57(25): 7523-7527, 2018 06 18.
Article in English | MEDLINE | ID: mdl-29645335

ABSTRACT

Tip-enhanced Raman spectroscopy can provide molecular fingerprint information with ultrahigh spatial resolution, but the tip will be easily contaminated, thus leading to artifacts. It also remains a great challenge to establish tip-enhanced fluorescence because of the quenching resulting from the proximity of the metal tip. Herein, we report shell-isolated tip-enhanced Raman and fluorescence spectroscopies by employing ultrathin shell-isolated tips fabricated by atomic layer deposition. Such shell-isolated tips not only show outstanding electromagnetic field enhancement in TERS but also exclude interference by contaminants, thus greatly promoting applications in solution. Tip-enhanced fluorescence has also been achieved using these shell-isolated tips, with enhancement factors of up to 1.7×103 , consistent with theoretical simulations. Furthermore, tip-enhanced Raman and fluorescence signals are acquired simultaneously, and their relative intensities can be manipulated by changing the shell thickness. This work opens a new avenue for ultrahigh resolution surface analysis using plasmon-enhanced spectroscopies.

13.
Clin Infect Dis ; 64(6): 719-727, 2017 03 15.
Article in English | MEDLINE | ID: mdl-27986673

ABSTRACT

Background: Despite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent. Methods: We included observational studies that applied either the tuberculin skin test or the interferon gamma release assay for diagnosis of LTBI and that provided adjusted effect estimate for the association between diabetes and LTBI. We searched PubMed and EMBASE through 31 January 2016. The risk of bias of included studies was assessed using a quality assessment tool modified from the Newcastle-Ottawa scale. Results: Thirteen studies (1 cohort study and 12 cross-sectional studies) were included, involving 38263 participants. The cohort study revealed an increased but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence interval [CI], 0.50-38.55). For the cross-sectional studies, the pooled odds ratio from the random-effects model was 1.18 (95% CI, 1.06-1.30), with a small statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment revealed several methodological issues, but the overall direction of biases would reduce the positive causal association between diabetes and LTBI. Conclusions: Diabetes was associated with a small but statistically significant risk for LTBI. Findings from this review could be used to inform future cost-effectiveness analysis on the impact of LTBI screening programs among diabetics.


Subject(s)
Diabetes Complications/epidemiology , Diabetes Mellitus/epidemiology , Latent Tuberculosis/complications , Latent Tuberculosis/epidemiology , Cohort Studies , Cross-Sectional Studies , Humans , Odds Ratio , Publication Bias
14.
Rheumatol Int ; 37(2): 273-279, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27844125

ABSTRACT

Previous cross-sectional studies have suggested an association between migraine and rheumatoid arthritis (RA), but no longitudinal study has been performed to evaluate the temporal relationship between the two conditions. The purpose of the present population-based, propensity score-matched cohort study was to investigate whether migraineurs are at a higher risk of developing RA. A total of 58,749 subjects aged between 20 and 90 years with at least two ambulatory visits with a diagnosis of migraine were recruited in the migraine group. We fit a logistic regression model that included age, sex, comorbid conditions, and socioeconomic status as covariates to compute the propensity score. The non-migraine group consisted of 58,749 propensity score-matched, randomly sampled subjects without migraine. The RA-free survival curves were generated using the Kaplan-Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of RA. During follow-up, 461 subjects in the migraine group and 220 in the non-migraine group developed RA. The incidence rate of RA was 3.18 (95% confidence interval [CI] 2.90-3.49) per 1000 person-years in the migraine group and 1.54 (95% CI 1.34-1.76) per 1000 person-years in the non-migraine group. Compared to the non-migraine group, the crude hazard ratio of RA for the migraine group was 2.15 (95% CI 1.82-2.56, P < 0.0001), and the multivariable-adjusted hazard ratio was 1.91 (95% CI 1.58-2.31, P < 0.0001). This study showed that patients with migraine had an increased risk of developing RA.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Migraine Disorders/complications , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/etiology , Female , Follow-Up Studies , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Risk , Young Adult
15.
Cephalalgia ; 36(14): 1316-1323, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26853806

ABSTRACT

BACKGROUND: The association between migraine and Parkinson's disease (PD) remains controversial. The purpose of the present population-based, propensity score-matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD. METHODS: A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD. RESULTS: During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non-migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25-2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group (p = 0.0041). CONCLUSIONS: This study showed an increased risk of developing PD in patients with migraine.


Subject(s)
Migraine Disorders/diagnosis , Migraine Disorders/epidemiology , Parkinson Disease/diagnosis , Parkinson Disease/epidemiology , Population Surveillance , Propensity Score , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Population Surveillance/methods , Risk Factors , Taiwan/epidemiology
16.
Am Heart J ; 169(4): 508-14, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25819857

ABSTRACT

OBJECTIVES: Previous studies on the risk of acute myocardial infarction (AMI) in patients with Parkinson disease (PD) have generated inconsistent results. The purpose of this population-based longitudinal follow-up study was to investigate whether incident PD is associated with an increased risk of AMI. METHODS: A total of 3,211 subjects with at least 2 ambulatory visits with the principal diagnosis of PD in 2001 were enrolled in the PD group. The non-PD group consisted of 3,211 propensity score-matched subjects without PD. The propensity scores were computed using a logistic regression model that included age, sex, preexisting comorbidities, and socioeconomic status. The 3-year AMI-free survival rates of the 2 groups were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression with patients matched by propensity score was used to estimate the effect of PD on subsequent occurrence of AMI. RESULTS: During the 3-year follow-up period, 83 subjects in the PD group and 53 in the non-PD group developed AMI (either fatal or nonfatal) events. The hazard ratio of AMI for the PD group compared with the non-PD group was 1.67 (95% CI 1.15-2.41, P = .0067). The AMI-free survival rate of the PD group was significantly lower than that of the non-PD group (P = .0032). The hazard ratios associated with PD for the combined end point 1 (AMI or cardiovascular death) and combined end point 2 (AMI or all-cause death) were 1.46 (95% CI 1.14-1.88, P = .0029) and 1.42 (95% CI 1.24-1.64, P < .0001), respectively. CONCLUSIONS: This study shows that PD is related to an increased risk of AMI. Further studies are required to investigate the mechanism underlying this association.


Subject(s)
Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Parkinson Disease/complications , Population Surveillance/methods , Risk Assessment/methods , Aged , Cause of Death/trends , Female , Follow-Up Studies , Humans , Incidence , Male , Prognosis , Propensity Score , Retrospective Studies , Risk Factors , Survival Rate/trends , Taiwan/epidemiology
17.
Am J Med Sci ; 368(1): 55-60, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38479487

ABSTRACT

BACKGROUND: This study aimed to investigate whether physical activity (PA) is associated with a lower risk of subsequently developing chronic obstructive pulmonary disease (COPD). METHODS: We conducted this population-based longitudinal follow-up study in a community in Taiwan. This study recruited 61,446 subjects who had participated in the Keelung Community-based Integrated Screening Program (KCIS) between 2005 and 2012. During their participation in KCIS, they were provided with structured questionnaires to collect their baseline characteristics, including weekly PA time. After excluding subjects diagnosed with COPD before they joined KCIS and/or who provided incomplete lifestyle data, 59,457 subjects remained, and were classified into three groups based on their weekly PA time: i.e., as NPA (no regular PA), LPA (low PA, <90 min/week) and HPA (high PA, ≥90 min/week). The primary outcome was a new diagnosis of COPD, followed up until the end of 2015 or their death. Cox proportional-hazard regression was used to assess the impact of PA on the risk of COPD. RESULTS: The risk of COPD was more than 20% lower in the LPA and HPA groups than in the NPA group. Specifically, the adjusted hazard ratio for the risk of COPD was 0.72 in the LPA group (95% CI, 0.61-0.85, p < 0.001) and 0.79 in the HPA group (95% CI, 0.69-0.90, p < 0.001). CONCLUSIONS: Our research uncovered an inverse relationship between PA and COPD. The findings suggest that PA might be useful as a strategy for the primary prevention of COPD.


Subject(s)
Exercise , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Taiwan/epidemiology , Male , Female , Middle Aged , Longitudinal Studies , Follow-Up Studies , Aged , Risk Factors , Adult
18.
Nat Commun ; 15(1): 3850, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719864

ABSTRACT

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.


Subject(s)
Bacillus subtilis , Bacterial Proteins , Cation Transport Proteins , Potassium , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Bacillus subtilis/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Binding Sites , Cation Transport Proteins/metabolism , Cation Transport Proteins/chemistry , Cryoelectron Microscopy , Crystallography, X-Ray , Models, Molecular , Potassium/metabolism , Protein Binding , Sodium/metabolism
19.
Int J Med Sci ; 10(10): 1375-86, 2013.
Article in English | MEDLINE | ID: mdl-23983599

ABSTRACT

PURPOSE: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. METHODS: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo. RESULTS: After transfection of GLUT-1 AS-ODNs: MTS assay showed the survival rates of radiation groups were reduced with the prolongation of culture time (p<0.05); Cell survival rates were significantly reduced along with the increasing of radiation dose (p<0.05). There was significant difference in the expression of GLUT-1mRNA and protein in the same X-ray dose between before and after X-ray radiation (p<0.05). In vivo, the expressions of GLUT-1 mRNA and protein after 8Gy radiation plus transfection of GLUT-1 AS-ODNs were significant decreased compared to 8Gy radiation alone (p<0.001). CONCLUSION: Radioresistance of laryngeal carcinoma may be associated with increased expression of GLUT-1 mRNA and protein. GLUT-1 AS-ODNs may enhance the radiosensitivity of laryngeal carcinoma mainly by inhibiting the expression of GLUT-1.


Subject(s)
Glucose Transporter Type 1/genetics , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/therapy , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Blotting, Western , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Line, Tumor , Cell Proliferation/drug effects , DNA, Antisense/genetics , DNA, Antisense/physiology , Flow Cytometry , Humans , Mice , Real-Time Polymerase Chain Reaction
20.
Brain Behav ; 13(4): e2972, 2023 04.
Article in English | MEDLINE | ID: mdl-36938834

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory, thinking, language, and, eventually, the ability to carry out the simplest of tasks. Tau protein, the major component of neurofibrillary tangles, is considered a key mediator of AD pathogenesis. The association between obstructive sleep apnea (OSA) and circulating tau remains unclear. The aim of the present meta-analysis was to evaluate the relationship between OSA and circulating tau via quantitative analysis. METHODS: A systematic search of Pubmed, Embase, and Web of Science were performed. The mean values of circulating total tau (T-tau) and phosphorylated tau (P-tau) in OSA and control groups were extracted. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using a random-effect model or fixed-effect model. RESULTS: A total of seven studies comprising 233 controls and 306 OSA patients were included in this study. The meta-analysis showed that the circulating T-tau level was significantly higher in OSA patients than those in the control group (SMD = 1.319, 95% CI = 0.594 to 2.044, z = 3.56, p < .001). OSA patients also had significantly higher circulating P-tau level than control group (SMD = 0.343, 95% CI = 0.122 to 0.564, z = 3.04, p = .002). CONCLUSIONS: The present meta-analysis demonstrated that both circulating T-tau and P-tau levels were significantly increased in OSA subjects when compared with non-OSA subjects. Larger sample-size studies on the association between OSA and circulating tau are still required to further validate our results.


Subject(s)
Sleep Apnea, Obstructive , tau Proteins , Sleep Apnea, Obstructive/blood , tau Proteins/blood , tau Proteins/metabolism , Humans , Phosphorylation
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