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1.
BMC Gastroenterol ; 24(1): 160, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730369

ABSTRACT

PURPOSE: The link between dietary fiber intake and Non-alcoholic fatty liver disease (NAFLD) is under exploration, yielding inconsistent findings. Considering the limitations of previous research and the significance of dietary fiber in hepatic steatosis, this study investigates the association between dietary fiber intake and Controlled Attenuation Parameter (CAP) among 5935 participants from the National Health and Nutrition Examination Survey (NHANES). MATERIALS AND METHODS: Multivariable regression was used to evaluate the association between dietary fiber intake and CAP. Smoothed curve fitting and threshold effect analysis techniques were applied to illustrate non-linear relationships. RESULTS: After adjusting for other variables, a negative correlation emerged between dietary fiber intake and CAP. Subgroup analysis by gender and race/ethnicity revealed a sustained negative association between dietary fiber intake and CAP among females and Whites. Additionally, an inverted U-shaped relationship was observed between dietary fiber intake and CAP among women and other race, with inflection points at 13.80 g/day and 33.45 g/day, respectively. CONCLUSION: Our research indicates that in the majority of Americans, there is an inverse relationship between dietary fiber intake and hepatic steatosis. This relationship exhibits an inverted U-shaped curve in women and other race, with a threshold effect. The findings of this study hold potential significance for clinical nutrition interventions, personalized dietary guidance, and advancing research into the diet-disease mechanism relationship.


Subject(s)
Dietary Fiber , Non-alcoholic Fatty Liver Disease , Nutrition Surveys , Humans , Dietary Fiber/administration & dosage , Female , Male , Non-alcoholic Fatty Liver Disease/epidemiology , Middle Aged , Adult , United States/epidemiology , Sex Factors
2.
Psychol Health Med ; 26(8): 991-1004, 2021 09.
Article in English | MEDLINE | ID: mdl-32490687

ABSTRACT

To explore the influence of sexuality-related factors on recent two-week morbidity and annual hospitalization in female migrant workers, 880 Chinese rural-to-urban female migrant workers aged 16-57 years were studied. Clustered logistic regression analyses revealed that women who never or seldom experienced lubrication difficulties had a lower risk of recent two-week morbidity (adjusted odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.17-0.60, P< 0.001; adjusted OR = 0.35, 95% CI = 0.18-0.69, P= 0.003) than those who always experienced lubrication difficulties; women who never felt a lack of sexual interest had a significantly lower risk of annual hospitalization (adjusted OR = 0.40, 95% CI = 0.20-0.79, P= 0.009) than those who always or seldom lacked sexual interest, and women who never felt sexual satisfaction had a higher risk of annual hospitalization (adjusted OR = 3.08, 95% CI = 1.75-5.42, P< 0.001) than those who always or seldom experienced sexual satisfaction. The independent contributions of sexuality-related factors to the risk of recent two-week morbidity and annual hospitalization were 5.8% and 29.5%, respectively. This study suggests that sexuality may have a modest influence on recent two-week morbidity and a dominant impact on annual hospitalization.


Subject(s)
Hospitalization , Morbidity , Sexuality , Transients and Migrants , China/epidemiology , Cross-Sectional Studies , Female , Hospitalization/statistics & numerical data , Humans , Risk Factors , Sexuality/statistics & numerical data , Transients and Migrants/psychology , Transients and Migrants/statistics & numerical data
3.
Am J Physiol Renal Physiol ; 319(2): F304-F311, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32567350

ABSTRACT

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD). Recently, our laboratory generated a mouse model with the typical phenotypes of AKI to CKD transition in the unilateral kidney. However, AKI, CKD, and even the transition from AKI to CKD usually occur bilaterally rather than unilaterally in patients. Therefore, in the present study, we further modified the strategy and developed a new model of CKD transitioned from bilateral ischemia-reperfusion injury (IRI) in C57BL/6 mice. In this new model, unilateral severe IRI was performed in one kidney while the contralateral kidney was kept intact to maintain animal survival; then, following 14 days of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was subjected to a similar IRI. Animals of these two-stage bilateral IRI models with pedicle clamping of 21 and 24 min at a body temperature of 37°C exhibited incomplete recovery from AKI and subsequent development of CKD with characteristics of progressive decline in glomerular filtration rate, increases in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis, in both kidneys. In conclusion, a new bilateral AKI to CKD transition animal model with a typical phenotype of CKD was generated in C57BL/6 mice.


Subject(s)
Acute Kidney Injury/complications , Acute Kidney Injury/pathology , Renal Insufficiency, Chronic/pathology , Reperfusion Injury/pathology , Animals , Disease Models, Animal , Fibrosis/metabolism , Glomerular Filtration Rate/physiology , Kidney/pathology , Male , Mice, Inbred C57BL , Proteinuria/physiopathology , Reperfusion Injury/complications
4.
Am J Physiol Renal Physiol ; 317(2): F286-F295, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31116604

ABSTRACT

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD), which is closely associated with the severity of AKI. However, the underlying mechanisms for the AKI to CKD transition remain unclear. Several animal models with AKI to CKD transition have been generated and widely used in research; however, none of them exhibit the typical changes in glomerular filtration rate or plasma creatinine, the hallmarks of CKD. In the present study, we developed a novel model with a typical phenotype of AKI to CKD transition in C57BL/6 mice. In this model, life-threatening ischemia-reperfusion injury was performed in one kidney, whereas the contralateral kidney was kept intact to maintain animal survival; then, after 2 wk of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was removed. Animals of this two-stage unilateral ischemia-reperfusion injury model with pedicle clamping of 21 and 24 min exhibited an incomplete recovery from AKI and subsequent progression of CKD with characteristics of a progressive decline in glomerular filtration rate, increase in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis. In conclusion, a new model of the AKI to CKD transition was generated in C57BL/6 mice.


Subject(s)
Acute Kidney Injury/etiology , Kidney , Renal Insufficiency, Chronic/etiology , Reperfusion Injury/complications , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Animals , Biomarkers/blood , Constriction , Creatinine/blood , Disease Models, Animal , Disease Progression , Fibrosis , Glomerular Filtration Rate , Kidney/metabolism , Kidney/physiopathology , Kidney/ultrastructure , Mice, Inbred C57BL , Nephrectomy , Organ Size , Phenotype , Proteinuria/etiology , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/physiopathology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Time Factors
5.
Am J Physiol Renal Physiol ; 317(3): F616-F622, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31291121

ABSTRACT

Transplanted kidneys usually experience several episodes of ischemia, including cold ischemia during allograft storage in preservation solution. However, previous studies focusing on cold renal ischemia were only carried out in vitro or ex vivo. In the present study, we developed and characterized an in vivo mouse model of renal ischemia-reperfusion injury (IRI) induced exclusively by cold ischemia. C57BL/6 mice underwent right kidney nephrectomy, and the left kidney was kept cool with circulating cold saline in a kidney cup, while body temperature was maintained at 37°C. We clamped the renal pedicle and flushed out the blood inside the kidney with cold saline via an opening on the renal vein. The severity of renal IRI was examined with different ischemic durations. We found that the mice with <2 h of cold ischemia exhibited no significant changes in renal function or histopathology; animals with 3 or 4 h of cold ischemia developed into mild to moderate acute kidney injury with characteristic features, including the elevation in plasma creatinine concentration and reduction in glomerular filtration rate and tubular necrosis, followed by a subsequent recovery. However, mice with 5 h of cold ischemia died in a few days with severe acute kidney injury. In summary, we generated a mouse model of renal IRI induced exclusively by cold ischemia, which mimics graft cold storage in preservation solution, and renal function can be evaluated in vivo.


Subject(s)
Acute Kidney Injury/etiology , Cold Ischemia , Kidney Transplantation , Kidney/blood supply , Reperfusion Injury/etiology , Acute Kidney Injury/blood , Acute Kidney Injury/pathology , Acute Kidney Injury/physiopathology , Animals , Antigens, CD/metabolism , Biomarkers/blood , Cadherins/metabolism , Creatinine/blood , Disease Models, Animal , Disease Progression , Glomerular Filtration Rate , Kidney/metabolism , Kidney/pathology , Kidney/physiopathology , Male , Mice, Inbred C57BL , Necrosis , Reperfusion Injury/blood , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Time Factors
6.
Clin Exp Hypertens ; 41(4): 373-380, 2019.
Article in English | MEDLINE | ID: mdl-30095294

ABSTRACT

OBJECTIVE: This study aimed to investigate the most notable obesity index and its optimal cut-off point of hypertension in different age groups stratified by sexes among community residents in southern China. METHODS: In this cross-sectional study, 620 men and 631 women aged 18-59 years were enrolled. The independent-samples t-test and chi-square test were conducted to analyze continuous and categorical variables, respectively. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis assessed the association between the obesity indices and hypertension risk. RESULTS: Waist-stature ratio (WSR) and waist-hip ratio (WHR) were the most notable risk factors for hypertension in young men and women, respectively. The odds ratios (ORs) of hypertension risk increased with per standard deviation (SD) in WSR and WHR (WSR: OR = 2.877, 95% confidence interval [CI] = 1.602 to 5.167; WHR: OR = 10.683, 95%CI = 2.179 to 52.376). In the middle-aged group of both sexes, body mass index (BMI) was the most distinctive risk factor for hypertension, the ORs of hypertension risk increased with per SD in BMI (men: OR = 2.297, 95%CI = 1.683 to 3.136; women: OR = 1.810, 95%CI = 1.338 to 2.450). ROC curve analysis demonstrated WSR and PI were better indicators than other indices among young men, and WSR was the best marker among young women. However, BMI and WC were the most sensitive markers in middle-aged men and women, respectively. CONCLUSIONS: In this Chinese population, the association of obesity indices and hypertension is inconsistent in different age groups and sexes. It is important to choose appropriate indicators for specific groups of people.


Subject(s)
Body Size , Hypertension/epidemiology , Adolescent , Adult , Age Factors , Aged , Body Height , Body Mass Index , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , ROC Curve , Risk Factors , Sex Factors , Waist Circumference , Waist-Hip Ratio , Young Adult
7.
Am J Physiol Renal Physiol ; 314(3): F381-F387, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29141940

ABSTRACT

storage is the most prevalent method for graft preservation in kidney transplantation (KTX). The protective effects of various preservation solutions have been studied extensively in both clinical trials and experimental animal models. However, a paucity of studies have examined the effect of different preservation solutions on graft function in mouse KTX; in addition, the tolerance of the transplanted grafts to further insult has not been evaluated, which was the objective of the present study. We performed mouse KTX in three groups, with the donor kidneys preserved in different solutions for 60 min: saline, mouse serum, and University of Wisconsin (UW) solution. The graft functions were assessed by kidney injury markers and glomerular filtration rate (GFR). The grafts that were preserved in UW solution exhibited better functions, reflected by 50 and 70% lower plasma creatinine levels as well as 30 and 55% higher plasma creatinine levels in GFR than serum and saline groups, respectively, during the first week after transplants. To examine the graft function in response to additional insult, we induced ischemia-reperfusion injury (IRI) by clamping the renal pedicle for 18 min at 4 wk after KTX. We found that the grafts preserved in UW solution exhibited ~30 and 20% less injury assessed by kidney injury markers and histology than in other two preservation solutions. Taken together, our results demonstrated that UW solution exhibited a better protective effect in transplanted renal grafts in mice. UW solution is recommended for use in mouse KTX for reducing confounding factors such as IRI during surgery.


Subject(s)
Kidney Transplantation , Kidney/drug effects , Kidney/surgery , Organ Preservation Solutions/pharmacology , Organ Preservation/methods , Reperfusion Injury/prevention & control , Saline Solution/pharmacology , Adenosine/pharmacology , Allopurinol/pharmacology , Animals , Biomarkers/blood , Creatinine/blood , Cytoprotection , Glomerular Filtration Rate/drug effects , Glutathione/pharmacology , Hepatitis A Virus Cellular Receptor 1/blood , Insulin/pharmacology , Kidney/metabolism , Kidney/physiopathology , Kidney Transplantation/adverse effects , Lipocalin-2/blood , Male , Mice, Inbred C57BL , Organ Preservation/adverse effects , Raffinose/pharmacology , Reperfusion Injury/blood , Reperfusion Injury/etiology , Reperfusion Injury/physiopathology , Time Factors
8.
Am J Physiol Renal Physiol ; 315(3): F628-F636, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29790388

ABSTRACT

Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild-type recipients or vice versa. Dual-kidney transplantation (DKT) provides a more physiological environment for recipients than single-kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications, and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher glomerular filtration rate (GFR) than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.


Subject(s)
Glomerular Filtration Rate , Hemodynamics , Kidney Transplantation/methods , Kidney/physiopathology , Kidney/surgery , Animals , Biomarkers/blood , Creatinine/blood , Graft Survival , Hepatitis A Virus Cellular Receptor 1/blood , Kidney/pathology , Kidney Transplantation/adverse effects , Lipocalin-2/blood , Male , Mice, Inbred C57BL , Models, Animal , Natriuresis , Recovery of Function , Renal Elimination , Sodium/urine , Time Factors
9.
Health Qual Life Outcomes ; 16(1): 33, 2018 Feb 13.
Article in English | MEDLINE | ID: mdl-29433527

ABSTRACT

BACKGROUND: Hospitalization over the last one year, an indicator of health service utilization, is an important and costly resource in older adult care. However, data on the relationship between functional status and annual hospitalization among older Chinese people are sparse, particularly for those with and without multimorbidity. In this study,we aimed to examine the association between functional status and annual hospitalization among community-dwelling older adults in Southern China, and to explore the independent contributions of socio-demographic variables, lifestyle and health-related factors and functional status to hospitalization in multimorbid and non-multimorbid groups. METHODS: This cross-sectional, community-based survey, studied 2603 older adults aged 60 years and above. Functional status was assessed by Functional Independence Measure (FIM). The outcome variable was any hospitalization over the last one year (annual hospitalization). Clustered logistic regression was used to analyze the independent contributions of FIM domains to annual hospitalization. RESULTS: Only in the multimorbid group, did the risk of annual hospitalization decrease significantly with increasing FIM score in walk domain (adjusted OR = 0.80 per SD increase, 95% CI = 0.70-0.91, P = 0.001) and its independent contribution accounted for 24.62%, more than that of socio-demographic variables (18.46%). However, among individuals without multimorbidity, there were no significant associations between FIM domains and annual hospitalization; thus, no independent contribution to the risk of hospitalization was observed. CONCLUSIONS: There exist some degree of correlation between functional status and annual hospitalization among older adults in Southern China, which might be due to the presence of multimorbidity with advanced age.


Subject(s)
Geriatric Assessment , Hospitalization/statistics & numerical data , Multimorbidity , Quality of Life , Activities of Daily Living , Aged , Case-Control Studies , China/epidemiology , Chronic Disease/epidemiology , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle Aged
10.
Front Nutr ; 11: 1367174, 2024.
Article in English | MEDLINE | ID: mdl-38846544

ABSTRACT

Purpose: The connection between magnesium and hepatic steatosis has not been well-studied. This study aimed to explore the link between magnesium intake and hepatic steatosis, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Materials and methods: The analysis included 5,935 participants, excluding individuals with hepatitis infection or substantial alcohol consumption. Magnesium intake assessment was based on 24-h dietary recalls. Hepatic steatosis evaluation employed the controlled attenuation parameter (CAP), measured via transient elastography. Multivariate regression and subgroup analyses were conducted to scrutinize the relationship between magnesium intake and CAP values. Results: A higher magnesium intake was associated with lower CAP values, after adjusting for potential confounders. Subgroup analyses indicated an inverted U-shaped correlation between magnesium intake and CAP in women, White people, and non-hypertensive individuals, with respective inflection points at 126, 124.5, and 125 mg/day, respectively. Below these thresholds, a higher magnesium intake correlated with increased CAP values, while above these points, it was associated with decreased CAP. Conclusion: This extensive population-based study indicates an inverse relationship between magnesium intake and hepatic steatosis in Americans. This relationship displays an inverted U-curve, varying before and after specified inflection points in women, White people, and non-hypertensive individuals. These findings offer insights into tailored magnesium supplementation strategies for preventing and treating liver steatosis, based on gender and ethnicity.

11.
Int Immunopharmacol ; 127: 111329, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38091832

ABSTRACT

BACKGROUND: SMYD3 refers to a histone lysine methyltransferase from the SMYD family, which acts as a gene transcriptional regulator chiefly through catalysis of the histone subunit 3 at lysine 4 trimethylation (H3K4me3). Great progress has been made that epigenetic modification plays a pivotal role in regulating macrophage polarization. However, the effects of the histone lysine methyltransferase SMYD3 on macrophage polarization and phenotypic switching are unclear. RESULTS: We found that LPS/IFN-γ-stimulated macrophages gradually transformed from M1 to M2 in the late stage, and SMYD3 played a key role in this process. As demonstrated by RNA-seq assessment, SMYD3 prominently activated a metabolic pathway known as TCA cycle inside macrophages during M1-M2 conversion. Besides, by modifying H3K4me3 histone, the target genes regulated by SMYD3 were identified via the ChIP-seq assessment, including citrate synthase (CS), succinate dehydrogenase complex subunit C (SDHC) and pyruvate carboxylase (PC). SMYD3 activated the transcriptional activities of the metabolic enzymes CS, SDHC and PC through H3K4me3 by causing the aggregation of citrate, an intramacrophage metabolite, and the depletion of succinate. And additionally, it facilitated the generation of ROS, as well as the expressions of genes associated with mitochondrial respiratory chain complexes. This increased ROS production ultimately induced mitophagy, triggering the M1 to M2 phenotype switch in the macrophages. CONCLUSIONS: Our study provides a detailed intrinsic mechanism in the macrophage phenotypic transition process, in short, SMYD3 promotes the M1-M2 conversion of macrophages by activating the TCA cycle through the simultaneous regulation of the transcriptional activities of the metabolic enzymes CS, SDHC and PC.


Subject(s)
Histones , Macrophages , Histones/metabolism , Reactive Oxygen Species/metabolism , Macrophages/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Epigenesis, Genetic
12.
Biotechnol Genet Eng Rev ; : 1-20, 2023 Apr 17.
Article in English | MEDLINE | ID: mdl-37066859

ABSTRACT

This research wasdesigned to provide a visual analysis of the current status, hotspots, and trends of global acupuncture for dysmenorrhea over the past 2 decades. The literature about acupuncture for dysmenorrhea from the Web of Science Core Collection database. Cite Space (5.6.R3) was used to analyze the volume of publications, journals, authors, cited journals, cited authors, countries, cited references, institutions, and keywords by using standard bibliometric measures. The most productive countries and institutions in this area were China (79) and BeijingUniversity of Chinese Medicine (24). The Evidence-Based Complementary and Alternative Medicine was the most published journal (29) and also had the highest number of citations (80). The article by Woo HL (2018) (number of citations: 13) and the article by (centrality: 0.38) were the most representative references. JiangZhu (17) was the most productive author and Dawood MY (47) was the top cited author. The number one keyword in terms of frequency and centrality was 'primary dysmenorrhea", and the leading hotspot from 2002 to 2022 was "Functional connectivity". The three forefront topics were "prevalence", "impact"and "point'. This research is thefirst bibliometric analysis of the current situation and new trends about acupuncture for dysmenorrhea in the past 20 years using CiteSpace. It offered some information on acupuncture for dysmenorrhea and valuable information for researchers to identify prospective collaborators, partner institutions, popular topics, and research frontiers.

13.
Wideochir Inne Tech Maloinwazyjne ; 18(3): 533-540, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37868285

ABSTRACT

Introduction: Laparoscopic minimally invasive surgery has been widely used in the diagnosis and treatment of gynaecological diseases. Aim: To investigate the effect of dexmedetomidine on perioperative haemodynamics and cognitive function in elderly gynaecological patients who underwent laparoscopic surgery. Material and methods: Clinical baseline characteristics, haemodynamic parameters, renin activity, norepinephrine level, cognitive function, pain level, and sedation were compared between the 2 groups. Results: At T4 (10 min after extubation) and T5 (1 h after extubation), significant differences were found in systolic blood pressure, diastolic blood pressure, and heart rate between the 2 groups (p < 0.05); renin activity and norepinephrine level were much lower in the dexmedetomidine group than in the control group at T3 (10 min before extubation) and T4 (p < 0.05). One day before surgery, there were no significant differences in Mini-mental state examination (MMSE), visual analogue scale (VAS), and Ramsay scores between the 2 groups (p > 0.05), but the MMSE score 1 day after surgery and the Ramsay score at 12 h after surgery in the dexmedetomidine group were much higher than that in the control group (p < 0.05). Notably, at 2, 4, 12, 24, and 48 h after surgery, the VAS score in the dexmedetomidine group was significantly lower than that in the control group (p < 0.05). Conclusions: Dexmedetomidine has a better clinical effect in improving perioperative haemodynamics and early cognitive function in elderly gynaecological patients who received laparoscopic surgery.

14.
Am J Physiol Regul Integr Comp Physiol ; 302(7): R815-24, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22262306

ABSTRACT

Neurons that synthesize melanin-concentrating hormone (MCH) colocalize GABA, regulate energy homeostasis, modulate water intake, and influence anxiety, stress, and social interaction. Similarly, vasopressin and oxytocin can influence the same behaviors and states, suggesting that these neuropeptides may exert part of their effect by modulating MCH neurons. Using whole cell recording in MCH-green fluorescent protein (GFP) transgenic mouse hypothalamic brain slices, we found that both vasopressin and oxytocin evoked a substantial excitatory effect. Both peptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent and tetrodotoxin-resistant manner, indicating a direct effect. Substitution of lithium for extracellular sodium, Na(+)/Ca(2+) exchanger blockers KB-R7943 and SN-6, and intracellular calcium chelator BAPTA, all substantially reduced the vasopressin-mediated depolarization, suggesting activation of the Na(+)/Ca(2+) exchanger. Vasopressin reduced input resistance, and the vasopressin-mediated depolarization was attenuated by SKF-96265, suggesting a second mechanism based on opening nonselective cation channels. Neither vasopressin nor oxytocin showed substantial excitatory actions on lateral hypothalamic inhibitory neurons identified in a glutamate decarboxylase 67 (GAD67)-GFP mouse. The primary vasopressin receptor was vasopressin receptor 1a (V1aR), as suggested by the excitation by V1aR agonist [Arg(8)]vasotocin, the selective V1aR agonist [Phe(2)]OVT and by the presence of V1aR mRNA in MCH cells, but not in other nearby GABA cells, as detected with single-cell RT-PCR. Oxytocin receptor mRNA was also detected in MCH neurons. Together, these data suggest that vasopressin or oxytocin exert a minimal effect on most GABA neurons in the lateral hypothalamus but exert a robust excitatory effect on presumptive GABA cells that contain MCH. Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells.


Subject(s)
Arginine Vasopressin/physiology , GABAergic Neurons/physiology , Hypothalamic Hormones/physiology , Hypothalamus/physiology , Melanins/physiology , Oxytocin/physiology , Pituitary Hormones/physiology , Animals , Arginine Vasopressin/agonists , Arginine Vasopressin/pharmacology , Benzyl Compounds/pharmacology , Calcium Channel Blockers/pharmacology , Calcium Channels/drug effects , Chelating Agents/pharmacology , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , GABAergic Neurons/drug effects , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/physiology , Hypothalamus/drug effects , Imidazoles/pharmacology , Ion Channels/drug effects , Lithium/pharmacology , Membrane Potentials/drug effects , Mice , Mice, Transgenic , Oxytocin/pharmacology , Receptors, Oxytocin/physiology , Receptors, Vasopressin/agonists , Receptors, Vasopressin/physiology , Sodium-Calcium Exchanger/antagonists & inhibitors , Sodium-Calcium Exchanger/physiology , Thiazolidines/pharmacology , Thiourea/analogs & derivatives , Thiourea/pharmacology
15.
Am J Clin Pathol ; 157(3): 426-433, 2022 Mar 03.
Article in English | MEDLINE | ID: mdl-34596209

ABSTRACT

OBJECTIVES: This study reviewed the institutional experience of performing calcitonin immunostain on an additional ThinPrep slide in fine-needle aspiration (FNA) diagnosis of medullary thyroid carcinoma (MTC). METHODS: Thyroid FNA cases with MTC suspected or included in the differential diagnosis during cytologic evaluation and calcitonin immunostain performed were retrieved and reviewed. RESULTS: Calcitonin immunostain was performed in 132 cases with 41 positive, 81 negative, and 10 indeterminate results. All calcitonin-positive cases had a cytologic diagnosis of MTC while all calcitonin-negative cases were cytologically classified as non-MTCs except for two cases suspicious for MTC. In 10 cases with an indeterminate calcitonin result, diagnoses of non-MTC and suspicious for MTC were rendered in 6 and 4 cases, respectively. Histopathologic follow-up was available in 85 (64%) cases. All cytologically diagnosed MTC cases were confirmed on histopathology. In 3 MTC cases with an indeterminate calcitonin result, 1 case was misclassified cytologically as follicular neoplasm. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of calcitonin immunostain were all 100% for diagnosing MTC. CONCLUSIONS: Our study demonstrates the feasibility of performing calcitonin immunostain on an additional ThinPrep slide. Calcitonin immunocytochemistry is a valuable adjunct test for FNA diagnosis and differential diagnosis of MTC.


Subject(s)
Carcinoma, Neuroendocrine , Thyroid Neoplasms , Thyroid Nodule , Biopsy, Fine-Needle/methods , Calcitonin , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/pathology , Humans , Immunohistochemistry , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Nodule/pathology
16.
ACS Appl Mater Interfaces ; 14(5): 7082-7092, 2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35076207

ABSTRACT

Selenium-heterocyclic and side-chain strategies for developing near-infrared (NIR) small fused-ring acceptors (FRAs) to further obtain short-circuit current density (Jsc) have proven advantageous in the top-performing polymer solar cells (PSCs). Herein, a new electron-rich central selenium-containing heterocycle core (BTSe) attaching alkyl side chains with a terminal phenyl group was coupled with a difluorinated and dichlorinated electron-accepting terminal 1,1-dicyanomethylene-3-indanone (IC) to afford two types of new FRAs, BTSe-IC2F and BTSe-IC2Cl. Interestingly, in spite of the weaker intramolecular charge transfer, BTSe-IC2F shows a stronger NIR response because of the smaller bandgap (Egopt) up to 1.26 eV, benefiting from the stronger ordered molecular packing in comparison to BTSe-IC2Cl with an Egopt of 1.30 eV. Additionally, thermal annealing induced an evident red shift by ∼50 nm in the absorption of D18:BTSe-IC2F blend films. Such a phenomenon may be attributed to the synergistic impact of the formation of inward constriction toward the molecular backbone because of the combination of bulky side chains and fluorinated IC as well as the reduced aromaticity of the selenium heterocycle. Consequently, the thermally annealed device based on BTSe-IC2F/D18 achieves a champion power conversion efficiency (PCE) of 17.3% with a high fill factor (FF) of 77.22%, which is among the highest reported PCE values for selenium-heterocyclic FRAs in binary PSCs. The improved Jsc and FF values of the D18:BTSe-IC2F film are simultaneously achieved mainly because of the preferred face-on orientations, the well-balanced electron/hole mobility, and the favorable blend morphology compared to D18:BTSe-IC2Cl. This work suggests that the selenium-heterocyclic fused-ring core (with proper side chains) combined with fluorinated terminal groups is an effective strategy for obtaining highly efficient NIR-responsive FRAs.

17.
Sci Transl Med ; 14(635): eabj4906, 2022 03 09.
Article in English | MEDLINE | ID: mdl-35263146

ABSTRACT

Renal ischemia-reperfusion injury is an important contributor to the development of delayed graft function after transplantation, which is associated with higher rejection rates and poorer long-term outcomes. One of the earliest impairments during ischemia is Na+/K+-ATPase (Na/K pump) dysfunction due to insufficient ATP supply, resulting in subsequent cellular damage. Therefore, strategies that preserve ATP or maintain Na/K pump function may limit the extent of renal injury during ischemia-reperfusion. Here, we applied a synchronization modulation electric field to activate Na/K pumps, thereby maintaining cellular functions under ATP-insufficient conditions. We tested the effectiveness of this technique in two models of ischemic renal injury: an in situ renal ischemia-reperfusion injury model (predominantly warm ischemia) and a kidney transplantation model (predominantly cold ischemia). Application of the synchronization modulation electric field to a renal ischemia-reperfusion injury mouse model preserved Na/K pump activity, thereby reducing kidney injury, as reflected by 40% lower plasma creatinine (1.17 ± 0.03 mg/dl) in the electric field-treated group as compared to the untreated control group (1.89 ± 0.06 mg/dl). In a mouse kidney transplantation model, renal graft function was improved by more than 50% with the application of the synchronization modulation electric field according to glomerular filtration rate measurements (85.40 ± 12.18 µl/min in the untreated group versus 142.80 ± 11.65 µl/min in the electric field-treated group). This technique for preserving Na/K pump function may have therapeutic potential not only for ischemic kidney injury but also for other diseases associated with Na/K pump dysfunction due to inadequate ATP supply.


Subject(s)
Reperfusion Injury , Sodium-Potassium-Exchanging ATPase , Adenosine Triphosphate , Animals , Ischemia , Kidney/metabolism , Mice , Sodium-Potassium-Exchanging ATPase/metabolism
18.
J Neurosci ; 30(30): 10205-19, 2010 Jul 28.
Article in English | MEDLINE | ID: mdl-20668204

ABSTRACT

The neuropeptide kisspeptin is necessary for reproduction, fertility, and puberty. Here, we show strong kisspeptin innervation of hypothalamic anorexigenic proopiomelanocortin (POMC) cells, coupled with a robust direct excitatory response by POMC neurons (n > 200) to kisspeptin, mediated by mechanisms based on activation of a sodium/calcium exchanger and possibly opening of nonselective cation channels. The excitatory actions of kisspeptin on POMC cells were corroborated with quantitative PCR data showing kisspeptin receptor GPR54 expression in the arcuate nucleus, and the attenuation of excitation by the selective kisspeptin receptor antagonist, peptide 234. In contrast, kisspeptin inhibits orexigenic neuropeptide Y (NPY) neurons through an indirect mechanism based on enhancing GABA-mediated inhibitory synaptic tone. In striking contrast, gonadotropin-inhibiting hormone (GnIH and RFRP-3) and NPY, also found in axons abutting POMC cells, inhibit POMC cells and attenuate the kisspeptin excitation by a mechanism based on opening potassium channels. Together, these data suggest that the two central peptides that regulate reproduction, kisspeptin and GnIH, exert a strong direct action on POMC neurons. POMC cells may hypothetically serve as a conditional relay station downstream of kisspeptin and GnIH to signal the availability of energy resources relevant to reproduction.


Subject(s)
Arcuate Nucleus of Hypothalamus/cytology , Excitatory Postsynaptic Potentials/drug effects , Neurons/drug effects , Neuropeptide Y/metabolism , Pro-Opiomelanocortin/metabolism , Tumor Suppressor Proteins/pharmacology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Axons/metabolism , Calcium Channel Blockers/pharmacology , Chelating Agents/pharmacology , Dose-Response Relationship, Drug , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/physiology , Female , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Green Fluorescent Proteins/genetics , Imidazoles/pharmacology , In Vitro Techniques , Kisspeptins , Male , Membrane Potentials/drug effects , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurons/cytology , Neurons/metabolism , Patch-Clamp Techniques/methods , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, Kisspeptin-1 , Renilla/genetics , Sodium-Calcium Exchanger/antagonists & inhibitors , Thiourea/analogs & derivatives , Thiourea/pharmacology , Tumor Suppressor Proteins/metabolism
19.
Kidney Med ; 3(3): 433-437, 2021.
Article in English | MEDLINE | ID: mdl-34136788

ABSTRACT

The occurrence of renal amyloidosis and fibrillary glomerulonephritis in the same biopsy specimen is exceptional and poses a diagnostic challenge. We describe the case of a non-Hispanic White patient with end-stage kidney disease due to fibrillary glomerulonephritis who received a second living donor kidney from a Hispanic individual. A 40-month-posttransplantation biopsy performed for an elevated serum creatinine level revealed interstitial congophilic deposits and glomerular noncongophilic fibrillary deposits, in addition to rejection. Separate laser microdissections of the glomerular and interstitial deposits followed by liquid chromatography-tandem mass spectrometry (LC MS/MS) revealed DNAJB9 peptide spectra in glomeruli and a peptide profile consistent with leukocyte chemotactic factor 2 (ALECT2) amyloidosis in the interstitium. Based on these findings, a 2-week-posttransplantation biopsy was re-reviewed and analyzed using LC MS/MS, which revealed a peptide profile consistent with ALECT2 amyloidosis in the interstitium, without peptide spectra for ALECT2 or DNAJB9 in glomeruli. The findings were consistent with donor-derived ALECT2 amyloidosis and recurrent fibrillary glomerulonephritis. At 49 months posttransplantation, allograft function was stable with minimal proteinuria. Thus, LC MS/MS was crucial to establish the accurate diagnosis of these 2 nephropathies characterized by fibrillary deposits. The indolent posttransplantation course suggests that donated kidneys with focal interstitial ALECT2 deposits may be suitable for transplantation but the deposits persist for many years.

20.
ACS Appl Mater Interfaces ; 13(11): 13254-13263, 2021 Mar 24.
Article in English | MEDLINE | ID: mdl-33689285

ABSTRACT

Inspired by the structural advantages of spiro-OMeTAD, which is the most commonly used hole-transporting material (HTM), two rationally designed HTMs with butterfly-shaped triarylamine groups based on dibenzofulvene-bridged indacenodithiophene (IDT) core (attaching hexyl and octyl chains) have been synthesized, namely, IT-C6 and IT-C8, respectively. Shorter alkyl-chain-based IT-C6 exhibits a marked increase in glass-transition temperature (Tg) of 105 °C, whereas IT-C8 shows a Tg of 95 °C. Moreover, it is demonstrated that IT-C6 exhibits a higher hole-transporting mobility, more suitable band energy alignment, better interfacial contact, and passivation effect. The inverted devices of employed HTM based on IT-C6 obtained a champion PCE of 18.34% with a remarkable fill factor (FF) of 82.32%, whereas the IT-C8-based device delivered an inferior PCE of 16.94% with an FF up to 81.20%. Both HTMs embodied inverted devices present high FF values greater than 81%, which are among the highest reported values of small molecular HTM-based PSCs. This work reveals that cutting off the symmetrical spiro-core and subsequently combining IDT (attaching tailored alkyl chains) with the spiro-linkage fluorine to construct the orthogonal molecular conformation is a significant principle for the design of promising dopant-free HTMs.

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