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1.
Opt Lett ; 49(6): 1571-1574, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489453

ABSTRACT

Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.

2.
Nutr J ; 23(1): 65, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886740

ABSTRACT

BACKGROUND: Time-restricted eating (TRE), a popular form of intermittent fasting, has shown benefits for improving metabolic diseases and cardiometabolic health. However, the effect of TRE in the regulation of blood pressure in primary hypertension remains unclear. METHODS: A 6-week randomized controlled trial was conducted, in which a total of 74 stage 1 primary hypertensive patients without high-risk were randomly assigned to Dietary Approaches to Stop Hypertension (DASH) group (n = 37) or DASH + TRE group (n = 37). Participants in the DASH + TRE group were instructed to consume their food within an 8-h window. Scientific research platform in We Chat application was used to track participants. The primary outcome was blood pressure. The secondary outcomes included body composition, cardiometabolic risk factors, inflammation-related parameters, urinary Na+ excretion, other clinical variables and safety outcomes. RESULTS: The reduction of systolic blood pressure and diastolic blood pressure were 5.595 ± 4.072 and 5.351 ± 5.643 mm Hg in the DASH group and 8.459 ± 4.260 and 9.459 ± 4.375 mm Hg in the DASH + TRE group. DASH + TRE group improved blood pressure diurnal rhythm. Subjects in DASH + TRE group had decreased extracellular water and increased urinary Na+ excretion. Furthermore, the decrease in blood pressure was associated with a reduction of extracellular water or increase in urinary Na+ excretion. In addition, safety outcomes such as nighttime hunger were also reported. CONCLUSION: Our study demonstrated that 8-h TRE + DASH diet caused a greater decrease in blood pressure in stage 1 primary hypertensive patients than DASH diet. This study may provide novel insights into the benefits of lifestyle modification in the treatment of primary hypertension. TRIAL REGISTRATION: https://www.chictr.org.cn/ (ChiCTR2300069393, registered on March 15, 2023).


Subject(s)
Blood Pressure , Dietary Approaches To Stop Hypertension , Hypertension , Humans , Female , Male , Dietary Approaches To Stop Hypertension/methods , Middle Aged , Hypertension/diet therapy , Hypertension/therapy , Fasting , Adult , Treatment Outcome
3.
Clin Exp Hypertens ; 45(1): 2276029, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37943619

ABSTRACT

BACKGROUND: Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na+ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension. METHODS AND RESULTS: 603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na+ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na+ excretion were independent factors related to circulating TSP2. Mantel-Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ2 = 35.737) and DBP (χ2 = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901. CONCLUSION: Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na+ excretion, insulin resistance, and/or endothelial function.


Subject(s)
Hypertension , Insulin Resistance , Humans , Ankle Brachial Index , Pulse Wave Analysis , Thrombospondins , Sodium , Blood Pressure , Essential Hypertension/complications , Biomarkers
4.
Opt Express ; 30(15): 26912-26930, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-36236874

ABSTRACT

Terahertz (THz) radiations from graphene are expected to provide a powerful light source for their wide applications. However, their conversion efficiencies are limited with either long-duration or few-cycle single-color laser pulses. Here, we theoretically demonstrate that THz waves can be efficiently generated from monolayer graphene by using a long-duration two-color laser pulse at normal incidence. Our simulated results show that low-frequency THz emissions are sensitive to the phase difference between two colors, the laser intensity, and the fundamental wavelength. Their dependence on these parameters can be very well reproduced by asymmetry parameters accounting for electron populations of conduction and valence bands. On the contrary, a newly defined σ parameter including the Landau-Zener tunneling probability cannot precisely predict such dependence. Furthermore, the waveform of THz electric field driven by two-color laser pulses exhibits the typical feature of a half-cycle pulse.

5.
Opt Lett ; 47(15): 3816-3819, 2022 Aug 01.
Article in English | MEDLINE | ID: mdl-35913322

ABSTRACT

The two-color strong-field mixing in gas medium is a widely used approach to generate bright broadband terahertz (THz) radiation. Here, we present a new, to the best of our knowledge, and counterintuitive method to promote THz performance in the two-color scheme. Beyond our knowledge that the maximum THz generation occurs with two-color foci overlapped, we found that, when the foci of two-color beams are noticeably separated along the propagation axis resulting in cascading plasmas, the THz conversion efficiency is surged by one order of magnitude and the bandwidth is stretched by more than two times, achieving 10-3 conversion efficiency and >100 THz bandwidth under the condition of 800/400 nm, ∼35 fs driving lasers. With the help of the pulse propagation equation and photocurrent model, the observations can be partially understood by the compromise between THz generation and absorption due to the spatial redistribution of laser energy in cascading plasmas. The present method can be extended to a mid-infrared driving laser, and new records of THz peak power and conversion efficiency are expected.

6.
Psychol Med ; 52(1): 48-56, 2022 01.
Article in English | MEDLINE | ID: mdl-32501194

ABSTRACT

BACKGROUND: Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months. RESULTS: Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an 'enriched' randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization. CONCLUSIONS: The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.


Subject(s)
Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/prevention & control , Bayes Theorem , Antidepressive Agents/therapeutic use , Recurrence , Chronic Disease
7.
Int J Mol Sci ; 23(3)2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35163447

ABSTRACT

Botrytis cinerea is considered an important plant pathogen and is responsible for significant crop yield losses. With the frequent application of commercial fungicides, B. cinerea has developed resistance to many frequently used fungicides. Therefore, it is necessary to develop new kinds of fungicides with high activity and new modes of action to solve the increasingly serious problem of resistance. During our screening of fungicide candidates, one novel sulfonamide compound, N-(2-trifluoromethyl-4-chlorphenyl)-2-oxocyclohexyl sulfonamide (L13), has been found to exhibit good fungicidal activity against B. cinerea. In this work, the mode of action of L13 against B. cinerea and the field control effect on tomato gray mold was studied. L13 had good control against B. cinerea resistant to carbendazim, diethofencarb, and iprodione commercial fungicides in the pot culture experiments. SEM and TEM observations revealed that L13 could cause obvious morphological and cytological changes to B. cinerea, including excessive branching, irregular ramification or abnormal configuration, and the decomposition of cell wall and vacuole. L13 induced more significant electrolyte leakage from hyphae than procymidone as a positive control. L13 had only a minor effect on the oxygen consumption of intact mycelia, with 2.15% inhibition at 50 µg/mL. In two locations over 2 years, the field control effect of L13 against tomato gray mold reached 83% at a rate of 450 g ai ha-1, better than the commercial fungicide of iprodione. Moreover, toxicological tests demonstrated the low toxicological effect of L13. This research seeks to provide technical support and theoretical guidance for L13 to become a real commercial fungicide.


Subject(s)
Botrytis/growth & development , Fungicides, Industrial/pharmacology , Plant Diseases/prevention & control , Solanum lycopersicum/growth & development , Sulfonamides/pharmacology , Administration, Cutaneous , Administration, Oral , Animals , Botrytis/drug effects , Botrytis/metabolism , Cell Wall/drug effects , Drug Resistance, Fungal , Fungicides, Industrial/administration & dosage , Fungicides, Industrial/adverse effects , Solanum lycopersicum/microbiology , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Molecular Structure , Rabbits , Rats , Skin/drug effects , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Vacuoles/drug effects , Vacuoles/metabolism
8.
Opt Express ; 29(2): 1613-1633, 2021 Jan 18.
Article in English | MEDLINE | ID: mdl-33726372

ABSTRACT

With the parallel and perpendicular components of high harmonics generated by using aligned N2 molecules, we propose a method to retrieve the alignment distribution induced by the aligning laser based on the quantitative rescattering theory. And the intensity of pump laser and gas temperature can be precisely determined as well. We find that the intensity ratio between two harmonic components is very sensitive to the inclusion of multiple-orbital contribution in the theory. We thus suggest that it could be used to identify the interference from inner orbitals by tuning input laser power or extending the spectral region of high harmonics.

9.
Mediators Inflamm ; 2020: 3736912, 2020.
Article in English | MEDLINE | ID: mdl-32214903

ABSTRACT

Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients. Numerous studies have demonstrated that multiple surgery/anesthesia during the neurodevelopmental period affects cognitive function, whereas a single anesthesia/surgery rarely causes cognitive dysfunction in adults. However, whether adults who undergo multiple anesthesia/surgery over a short period will experience cognitive dysfunction remains unclear. In this study, central nervous system inflammation and changes in cholinergic markers were investigated in adult mice subjected to multiple laparotomy procedures over a short period of time. The results showed that despite the increased expression of IL-6 and TNF-α in the hippocampus after multiple operations and the activation of microglia, multiple anesthesia/surgery did not cause a decline in cognitive function in adult mice. There were no changes in the cholinergic markers after multiple anesthesia/surgery.


Subject(s)
Anesthesia/methods , General Surgery/methods , Animals , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Interleukin-10/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Male , Mice , Mice, Inbred C57BL , Microglia/metabolism , Morris Water Maze Test , Random Allocation , Tumor Necrosis Factor-alpha/metabolism
10.
Appl Opt ; 58(34): 9443-9454, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31873536

ABSTRACT

In this paper, we investigate the propagation of partially coherent flat-topped (PCFT) beams through atmospheric turbulence along a slant path. Using wave optics simulation (WOS), we calculated the on-axis intensity of PCFT beams in both vacuum and turbulence links, finding that PCFT beams will self-focus during propagation and that the beam coherence length has a significant impact on this focusing phenomenon. The effects of the zenith angle and the source coherence length on the scintillation index and mean signal-to-noise ratio (SNR) are analyzed. Furthermore, taking into consideration the limitation of available devices, we examined the impacts of source coherence time and detector integration time on the performance of PCFT beams in slant links. WOS results indicate as much as an extra 2 dB SNR gain from PCFT beams in short links in comparison with Gaussian Schell-model beams.

11.
Biochem Biophys Res Commun ; 497(1): 173-180, 2018 02 26.
Article in English | MEDLINE | ID: mdl-29432732

ABSTRACT

Long non-coding RNAs are dysregulated in human hepatocellular carcinoma (HCC). We tested the potential effect of long non-coding RNA 00312 ("Lnc00312") on human HCC cell behavior in vitro and in vivo. Forced-expression of Lnc00312 by a lentiviral vector induced proliferation inhibition and apoptosis in HepG2 cells and primary human HCC cells. Lnc00312 downregulated cyclin B1 and induced G2-M cell cycle arrest in HCC cells. Restoring cyclin B1 expression by a cyclin B1 cDNA construct inhibited Lnc00312-induced cytotoxicity against HCC cells. Conversely, siRNA-mediated knockdown of Lnc00312 increased cyclin B1 expression and promoted HepG2 cell proliferation. In vivo, the growth of HepG2 xenograft tumors in severe combined immunodeficient (SCID) mice was largely inhibited after expression of Lnc00312. Significantly, Lnc00312 is downregulated in human HCC tissues, which is negatively correlated with the tumor grade. Overall, Lnc00312 inhibits human HCC cell proliferation in vitro and in vivo. Cyclin B1 could be a key target protein of Lnc00312 in human HCC cells.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Proliferation , Cyclin B/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , RNA, Long Noncoding/metabolism , Animals , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Male , Mice , Mice, SCID , Neoplasm Invasiveness , Tumor Cells, Cultured
12.
Opt Express ; 24(13): 14352-61, 2016 Jun 27.
Article in English | MEDLINE | ID: mdl-27410589

ABSTRACT

We present a systematic study of spectral and temporal structure of high-order harmonic generation (HHG) by solving accurately the time-dependent Schrödinger equation for a hydrogen atom in the multiphoton regime where the Keldysh parameter is greater unity. Combining with a time-frequency transform and an extended semiclassical analysis, we explore the role of quantum trajectory in HHG. We find that the time-frequency spectra of the HHG plateau near cutoff exhibit a decrease in intensity associated with the short- and long-trajectories when the ionization process is pushed from the multiphoton regime into the tunneling regime. This implies that the harmonic emission spectra in the region of the HHG plateau near and before the cutoff are suppressed. To see the generality of this prediction, we also present a time-dependent density-functional theoretical study of the effect of correlated multi-electron responses on the spectral and temporal structure of the HHG plateau of the Ar atom.

13.
Cytokine ; 79: 96-102, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26797477

ABSTRACT

AIM: The euglycemic-hyperinsulinemic clamp (EHC) is not available in most clinical settings and is costly, time consuming and invasive, and requires trained staff. Therefore, an accessible and inexpensive test to identify insulin resistance (IR) is needed. The aim of this study is to assess whether zinc-α2-glycoprotein (ZAG) index [Ln ZAG/homeostasis model assessment of IR (HOMA-IR)] is a better surrogate index for estimating IR or metabolic syndrome (MetS) compared with other surrogate indices. METHODS: We performed a population-based cross-sectional study. Two hundred healthy subjects, 102 polycystic ovary syndrome (PCOS) patients, 97 newly diagnosed type 2 diabetes mellitus (nT2DM) and 84 impaired glucose tolerance (IGT) subjects were enrolled. The EHC was performed to identify IR. Circulating ZAG and adiponectin levels were determined by ELISA. RESULTS: The ZAG index was significantly lower in participants with IR including IGT, nT2DM and PCOS than in those without IR. In addition, subjects with MetS had lower ZAG indices and higher the product of fasting triglycerides and glucose (TyG) indices than those without MetS. The ZAG index showed a significantly stronger association with M values than the other surrogate indices, whereas the TyG index showed a stronger association with MetS. The optimal cutoff value of the ZAG index for detection of IR was 2.97 with a sensitivity of 88% and a specificity of 91%, whereas the optimal cutoff value of TyG index for detection of MetS was 4.90 with a sensitivity of 82% and a specificity of 86%. CONCLUSION: The ZAG index is a better marker than the other surrogate indices for identifying IR, whereas the TyG index has high sensitivity and specificity for identifying MetS.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Glucose Intolerance/blood , Insulin Resistance/physiology , Metabolic Syndrome/blood , Polycystic Ovary Syndrome/blood , Seminal Plasma Proteins/blood , Triglycerides/blood , Adiponectin/blood , Adult , Aged , Cross-Sectional Studies , Diabetes Mellitus, Type 2/diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Glucose Intolerance/diagnosis , Humans , Male , Metabolic Syndrome/diagnosis , Middle Aged , Polycystic Ovary Syndrome/diagnosis , Zn-Alpha-2-Glycoprotein
14.
J Vis Exp ; (209)2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39141528

ABSTRACT

Stereotaxic injection of a specific brain region constitutes a fundamental experimental technique in basic neuroscience. Researchers commonly base their choice of stereotaxic injection parameters on mouse brain atlases or published materials that employed various populations/ages of mice and different stereotaxic equipment, necessitating further validation of the stereotaxic coordinate parameters. The efficacy of calcium imaging, chemogenetic, and optogenetic manipulations relies on the precise expression of reporter genes within the region of interest, often requiring several weeks of effort. Thus, it is a time-consuming task if the coordinates of the target brain region are not verified in advance. Using an appropriate dye instead of a virus and implementing cryosectioning, researchers can observe the injection site immediately following dye administration. This facilitates timely adjustments to coordinate parameters in cases where discrepancies exist between the actual injection site and the theoretical position. Such adjustments significantly enhance the accuracy of viral expression within the target region in subsequent experiments.


Subject(s)
Stereotaxic Techniques , Animals , Mice , Cryoultramicrotomy/methods , Brain/metabolism
15.
Cardiovasc Res ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39253990

ABSTRACT

AIMS: Organs modulating blood pressure are associated with a common cytokine known as adipokines. We chose Zinc-alpha2-glycoprotein (ZAG) due to its prioritized transcriptional level in the database. Previous studies showed that ZAG is involved in metabolic disorders. The aim of this study was to investigate its role in hypertension. METHODS AND RESULTS: Serum ZAG levels were assessed in hypertensive and healthy participants. Blood pressure was monitored in Azgp1-/- mice and other animal models by 24-hour ambulatory implanted telemetric transmitters and tail-cuff method. Multi-omics analysis of proteomics and metabolomics were performed to explore possible mechanisms. Serum ZAG levels were significantly decreased and associated with morning urine Na+ excretion in hypertensive participants in a cross-sectional study. This study firstly reported that Azgp1-/- mice exhibited increased blood pressure and impaired urinary Na+ excretion, which were restored by AAV9-mediated renal tubule Azgp1 rescue. Azgp1 knockout caused the reprogramming of renal lipid metabolism, and increased Na+/H+-exchanger (NHE) activity in the renal cortex. Administration with a NHE inhibitor EIPA reversed the impaired urinary Na+ excretion in Azgp1-/- mice. Moreover, the activity of carnitine palmitoyltransferase 1 (CPT1), a key enzyme of fatty acid ß-oxidation, was decreased, and the levels of malonyl-CoA, an inhibitor of CPT1, were increased in renal cortex of Azgp1-/- mice. Renal Cpt1 rescue improved urinary Na+ excretion and blood pressure in Azgp1-/- mice, accompanied by decreased renal fatty acid levels and NHE activity. Finally, administration of recombinant ZAG protein improved blood pressure and urinary Na+ excretion in SHRs. CONCLUSIONS: Deficiency of Azgp1 increased the malonyl CoA-mediated inhibition of CPT1 activity, leading to renal lipid metabolism reprogramming, resulting in accumulated fatty acids and increased NHE activity, subsequently decreasing urinary Na+ excretion and causing hypertension. These findings may provide a potential kidney-targeted therapy in the prevention and treatment of hypertension.

16.
Heliyon ; 10(16): e35862, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39224276

ABSTRACT

Pain sensitivity varies depending on both the state and age of an individual. For example, chronic pain is more common in older individuals, but the underlying mechanisms remain unknown. This study revealed that 18-month-old mice (aged) experienced more severe and long-lasting allodynia and hyperalgesia in the chronic constriction injury (CCI)-induced pain state compared to 2-month-old mice. Interestingly, the aged mice had a higher baseline mechanical pain threshold than the adult mice. The expression of spinal receptor-active modification protein 1 (RAMP1), as a key component and regulator of the calcitonin gene-related peptide (CGRP) receptor for nociceptive transmission from the periphery to the spinal cord, was reduced in the physiological state but significantly increased after CCI in the aged mice compared to the adult mice. Moreover, when RAMP1 was knocked down using shRNA, the pain sensitivity of adult mice decreased significantly, and CCI-induced allodynia in aged mice was reduced. These findings suggest that spinal RAMP1 is involved in regulating pain sensitivity in a state- and age-dependent manner. Additionally, interfering with RAMP1 could be a promising strategy for alleviating chronic pain in older individuals.

17.
Mucosal Immunol ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39251184

ABSTRACT

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut-brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1-KYN pathway in the intestine could be a promising therapeutic target for POCD.

18.
Ann Med ; 55(2): 2240422, 2023.
Article in English | MEDLINE | ID: mdl-37506182

ABSTRACT

Introduction: Bipolar disorder (BD) is a prevalent and disabling mental disorder characterized by disrupted circadian rhythms and impaired neurocognitive features, both of which fall under the major domains of Research Domain Criteria (RDoC). However, there is limited evidence regarding the interaction between circadian rhythms and long-term neurocognitive functioning. Therefore, this longitudinal cohort study protocol aims to explore whether circadian rhythm can predict changes in neurocognitive functioning over time in patients with BD.Methods: This study adopts a longitudinal cohort design, aiming to recruit 100 BD patients in either depressive or remitted states. Participants will undergo evaluations from clinical, circadian rhythm, and neurocognitive perspectives at baseline, 6-month, and 12-month follow-ups, involving questionnaires, actigraphy, and computed neurocognitive tests. We will examine both cross-sectional and longitudinal associations between participants' circadian rhythm patterns and neurocognitive functioning. Statistical analyses will employ Spearman correlation and mixed regression models.Discussion: We anticipate that circadian rhythms may serve as predictors of neurocognitive functioning changes. The findings of this study could offer supplementary insights into BD pathophysiology, potential treatment targets, and prediction.Trial Registration: This study has been registered with the Chinese Clinical Trial Registry under the registration code ChiCTR2200064922 on 21st October 2022.


Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/complications , Longitudinal Studies , Cross-Sectional Studies , Circadian Rhythm/physiology , Cohort Studies
19.
Free Radic Biol Med ; 200: 59-72, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36868433

ABSTRACT

Epidemiological studies show an association between low body selenium and the risk of hypertension. However, whether selenium deficiency causes hypertension remains unknown. Here, we report that Sprague-Dawley rats fed a selenium-deficient diet for 16 weeks developed hypertension, accompanied with decreased sodium excretion. The hypertension of selenium-deficient rats was associated with increased renal angiotensin II type 1 receptor (AT1R) expression and function that was reflected by the increase in sodium excretion after the intrarenal infusion of the AT1R antagonist candesartan. Selenium-deficient rats had increased systemic and renal oxidative stress; treatment with the antioxidant tempol for 4 weeks decreased the elevated blood pressure, increased sodium excretion, and normalized renal AT1R expression. Among the altered selenoproteins in selenium-deficient rats, the decrease in renal glutathione peroxidase 1 (GPx1) expression was most prominent. GPx1, via regulation of NF-κB p65 expression and activity, was involved in the regulation of renal AT1R expression because treatment with dithiocarbamate (PDTC), an NF-κB inhibitor, reversed the up-regulation of AT1R expression in selenium-deficient renal proximal tubule (RPT) cells. The up-regulation of AT1R expression with GPx1 silencing was restored by PDTC. Moreover, treatment with ebselen, a GPX1 mimic, reduced the increased renal AT1R expression, Na+-K+-ATPase activity, hydrogen peroxide (H2O2) generation, and the nuclear translocation of NF-κB p65 protein in selenium-deficient RPT cells. Our results demonstrated that long-term selenium deficiency causes hypertension, which is due, at least in part, to decreased urine sodium excretion. Selenium deficiency increases H2O2 production by reducing GPx1 expression, which enhances NF-κB activity, increases renal AT1R expression, causes sodium retention and consequently increases blood pressure.


Subject(s)
Hypertension , Selenium , Animals , Rats , Hydrogen Peroxide , Hypertension/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1/genetics , Selenium/deficiency , Sodium
20.
Toxicon ; 215: 17-27, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35688267

ABSTRACT

Aflatoxin B1 (AFB1), which widely exists in soil and crops, is the most toxic aflatoxin and a carcinogen to humans and animals. The liver is the main organ that processes AFB1 and other mycotoxins and is also the main target of AFB1 toxicity. Taurine is known to exhibit a variety of physiological and pharmacological functions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine in AFB1-induced liver injury in rats. The results showed that taurine inhibited the increase in hepatic injury indices, hepatic apoptosis and hepatic malondialdehyde (MDA) contents while significantly enhanced the hepatic activities of antioxidant enzymes and mitochondrial function-related indices in AFB1-poisoned rats. Meanwhile, the expression levels of key factors in the Nrf2 signalling pathway were upregulated while the expression levels of key proteins in the mitochondria-mediated apoptotic pathway were downregulated after taurine administration. The results showed that taurine can reverse AFB1-induced liver injury and abnormal apoptosis through activation of the Nrf2 signalling pathway and its downstream antioxidant enzymes, which further protects mitochondria from oxidative stress and the subsequent apoptotic pathway.


Subject(s)
Aflatoxin B1 , Chemical and Drug Induced Liver Injury, Chronic , Aflatoxin B1/metabolism , Aflatoxin B1/toxicity , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Apoptosis , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Liver , Mitochondria/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Rats , Taurine/metabolism , Taurine/pharmacology , Taurine/therapeutic use
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