Exploring the Correlation Between Varied Serum Iodine Nutritional Levels and Anti-Thyroglobulin Antibodies.

Iodine deficiency results in elevated thyroglobulin (Tg) concentrations, with high iodine Tg being more immunogenic than low iodine Tg. The study investigated the correlation between serum iodine concentration and thyroglobulin autoantibody (TgAb) levels across diverse iodine nutritional statuses as determined by urine iodine concentration (UIC). Demographic information was collected from 1,482 participants through a questionnaire. Blood and spot urine were collected to measure thyroid-stimulating hormone (TSH), TgAb, thyroid anti-peroxidase antibody (TPOAb), serum iodine (SIC), serum non-protein-bound iodine (snPBI), urine iodine (UIC), creatinine (UCr). The median UIC and SIC were 146.5 µg/L and 74.9 µg/L, respectively. A linear relationship was observed between SIC, snPBI, and serum-protein-bound iodine (sPBI) (P < 0.001). The 90% reference intervals for SIC, snPBI, and sPBI were 50.7-120.7 µg/L, 21.9-52.9 µg/L, and 19.7-77.9 µg/L, respectively. The prevalence of elevated TgAb levels was significantly higher in women than in men (P < 0.001). Both low and high levels of snPBI and sPBI were associated with an increased risk of elevated TgAb levels. In women, the risk of positive TgAb in the group below the reference value of snPBI (OR = 2.079, 95%CI: 1.166, 3.705) and sPBI (OR = 2.578, 95%CI: 1.419, 4.684) was higher. In men, the risk of positive TgAb in the group below the reference value of SIC was higher (OR = 3.395, 95%CI: 1.286, 8.962). Iodine might exert an influence on TgAb levels through its binding to proteins, primarily Tg, thereby altering the iodine content of Tg. The interplay of gender factors further enhanced the risk of TgAb emergence.

Effect of Cyclotorsion Compensation in Small Incision Lenticule Extraction Surgery for the Correction of Myopic Astigmatism: A Systematic Review and Meta-Analysis.

INTRODUCTION: Small incision lenticule extraction (SMILE) has made notable advancements in addressing myopic astigmatism. Nevertheless, the potential impact of cyclotorsion on surgical outcomes cannot be overlooked. This study aims to assess the effectiveness of cyclotorsion compensation technology in SMILE surgery for the correction of myopic astigmatism, examining its influence on postoperative visual quality. METHODS: A systematic review and meta-analysis were conducted. A comprehensive literature search was performed using databases, including PubMed, Web of Science, EMBASE, Cochrane Library, EBSCO, Scopus, CNKI, VIP, and Wan Fang. Studies meeting the criteria were selected and included. Data were independently extracted by three authors. Clinical outcome parameters were analyzed using Review Manager version 5.3. RESULTS: This meta-analysis included ten studies. The results showed that, compared with the control group (cyclotorsion compensation was not performed in SMILE), the following indicators in the cyclotorsion compensation group were: residual astigmatism (RA) [weighted mean difference (MD) = 0.73, 95% confidence interval (CI) + 0.26 to + 1.19, P = 0.002], spherical equivalent (SE) (MD = 1.99, 95% CI + 0.77 to + 3.21, P = 0.001), coma (MD = -0.06, 95% CI -0.08 to -0.04, P < 0.00001), higher-order aberrations (HOAs) (MD = -0.04, 95% CI -0.06 to -0.02, P < 0.0001), follow-up 6-month angle of error (AE) (MD = -2.67, 95% CI -3.71 to -1.63, P < 0.00001), and follow-up 6-month uncorrected distance visual acuity (UDVA) (MD = -0.05, 95% CI -0.08 to -0.01, P = 0.005), and the differences in results were statistically significant. However, the differences among correction index, index of success (IOS), targeted induced astigmatism (TIA), magnitude of error (ME), and spherical aberration (SA) were not statistically significant. CONCLUSION: Cyclotorsion compensation proves to be effective and predictable for correcting myopic astigmatism. The cyclotorsion compensation group demonstrated advantages over the control group in terms of postoperative residual astigmatism, and it induced fewer coma aberrations. Whether cyclotorsion compensation can lead to better visual quality remains to be seen, and further research on correcting myopic astigmatism through cyclotorsion compensation is warranted.

Application and Comparison of Different Regression Models in Iodine Balance Experiment on Women of Childbearing Age and Pregnant Women.

The iodine balance experiment is a traditional approach to evaluate the physiological requirement for iodine, while the simple linear regression model (SLM) and the mixed effects model (MEM) are two primary methods used to analyze iodine balance experiments. In the present study, we aimed to compare the effects of these two regression models on the evaluation of iodine balance experiments to investigate appropriate valuation methods. By constructing SLM and MEM, zero iodine balance values (IBV) were determined, and the evaluation effects were compared. No changes were made to the experimental data for women of childbearing age, and cutoff values of 600 µg/day and 1000 µg/day, respectively, were chosen for further processing of the experimental data for pregnant women. Equation combinations 1-3 (EC1-3) were obtained by fitting SLM, and zero IBV were calculated as 110.26 µg/day, 333.06 µg/day, and 434.84 µg/day, respectively. EC4-6 were obtained by fitting MEM, and zero IBV were calculated as 110.44 µg/day, 335.79 µg/day, and 418.06 µg/day, respectively. The inclusion of inter-measurement variation as a random factor in the MEM yielded EC7-8, which reduced the test power of the iodine balance experiment on women of childbearing age. Our study suggested that when experimental conditions were tightly controlled, with fewer uncertainties or significant influences, computationally straightforward and well-understood SLM was preferred. If some uncertain factors might cause large changes in the experimental results, it was advised to use a more "conservative" MEM to calculate the zero IBV. ClinicalTrials.gov Identifier: Registered at Clinicaltrials.gov, NCT03279315 (17th September 2017, retrospectively registered), NCT03710148 (18th October 2018, retrospectively registered).

ANGPTL3 negatively regulates IL-1ß-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly.

Interleukin-1ß (IL-1ß)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1ß, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Presently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1ß-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1ß-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain (FLD) and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.

Recent advances in 1,2,3- and 1,2,4-triazole hybrids as antimicrobials and their SAR: A critical review.

With the widespread use and sometimes even abuse of antibiotics, the problem of bacterial resistance to antibiotics has become very serious, and it is posing a great threat to global health. Therefore, development of new antibiotics is imperative. Triazoles are five-membered, nitrogen-containing aromatic heterocyclic scaffolds, with two isomeric forms, i.e. 1,2,3-triazole and 1,2,4-triazole. Triazole-containing compounds have a wide range of biological activities such as antibacterial, antifungal, anticancer, antioxidant, antitubercular, antimalarial, anti-HIV, anticonvulsant, anti-inflammatory, antiulcer, analgesic, and etc. The bioactivities and the diversity of triazole-containing drugs have attracted wide interest in these heterocycles. Various antibiotic triazole hybrids have been developed, and most of which have shown potent antimicrobial activities. In this review, we summarized the recent advances in triazole hybrids as potential antibacterial agents and their structure-activity relationships (SARs). The information gained through SAR studies will provide further insights into the development of new triazole antimicrobials.

Structural damage to the rat eye following long-term simulated weightlessness.

To better perform space missions and develop human spaceflights, the eye health of astronauts is receiving increasing attention from researchers. In this study, we used prolonged tail suspension to simulate microgravity cephalad fluid shift in space to observe intraocular pressure (IOP) changes, retinal structure, and optic nerve damage in rats. We observed significant choroidal thickening and optic nerve demyelination lesions in the rats in each experimental group. At the cellular level, retinal ganglion cells (RGCs) survival was significantly reduced, optic nerve oligodendrocytes were reduced, and apoptotic factors and microglia-mediated inflammation-related factors were detected in both the retina and optic nerve. The severity of these changes increased with increasing tails suspension time. In conclusion, simulated long-term microgravity can lead to slight intraocular pressure fluctuations, choroidal thickening, reduced RGCs survival, and optic nerve demyelination in rats.

Spaceflight-associated neuro-ocular syndrome: a review of potential pathogenesis and intervention.

With the continuing progress in space exploration, a new and perplexing condition related to spaceflight ocular syndrome has emerged in the past four decades. National Aeronautics and Space Administration (NASA) has named this condition "spaceflight-associated neuro-ocular syndrome" (SANS). This article gives an overview of the current research about SANS and traditional Chinese medicine (TCM) by analyzing the existing publications on PubMed and CNKI and reports from NASA about SANS, summarizing the potential pathogenesis of SANS and physical interventions for treating SANS, and discussing the feasibility of treating SANS with TCM. Due to the unique characteristics of the space environment, it is infeasible to conduct large-scale human studies of SANS. SANS may be the result of the interaction of multiple factors, including inflammation and fluid displacement in the optic nerve sheath and cerebrospinal fluid. We should pay attention to SANS. Visual function is not only related to the health of astronauts but also closely related to space operations. TCM has antioxidative stress and antiapoptotic effects and is widely used for optic nerve diseases. TCM has great potential to prevent SANS.

Emerging roles of angiopoietin-like proteins in inflammation: Mechanisms and potential as pharmacological targets.

Angiopoietin-like proteins (ANGPTLs), a family of eight secreted glycoproteins termed ANGTPL1-8, are involved in angiogenesis, lipid metabolism, cancer progression, and inflammation. Their roles in regulating lipid metabolism have been intensively studied, as some ANGPTLs are promising pharmacological targets for hypertriglyceridemia and associated cardiovascular disease. Recently, the emerging roles of ANGPTLs in inflammation have attracted great attention. First, elevated levels of multiple circulating ANGPTLs in inflammatory diseases make them potential disease biomarkers. Second, multiple ANGPTLs regulate acute or chronic inflammation via various mechanisms, including triggering inflammatory signaling through their action as ligands for integrin or forming homo- /hetero-oligomers to regulate signal transduction via extra- or intracellular mechanisms. As dysregulation of the inflammatory response is a critical trigger in many diseases, understanding the roles of ANGPTLs in inflammation will aid in drug/therapy development. Here, we summarize the roles, mechanisms, and potential therapeutic values for ANGPTLs in inflammation and inflammatory diseases.

Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma.

BACKGROUND: Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism. METHODS: Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation. RESULTS: The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma. CONCLUSION: By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.

USP15 potentiates NF-κB activation by differentially stabilizing TAB2 and TAB3.

Tumor necrosis factor α (TNFα)- and interleukin 1ß (IL-1ß)-induced nuclear factor-κB (NF-κB) activation play key roles in inflammation, immunity, and cancer development. Here, we identified one of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 15 (USP15), as a positive regulator in both TNFα- and IL-1ß-induced NF-κB activation. Overexpression of USP15 potentiated TNFα- or IL-1ß-triggered NF-κB activation and downstream gene transcription, whereas knockdown of USP15 had opposite effects. Mechanistically, upon TNFα stimulation, USP15 showed an enhanced interaction with transforming growth factor-ß activated kinase-1 (TAK1)-TAK1 binding protein (TAB) complex to inhibit the proteolysis of TAB2/3 by different pathways. Apart from deubiquitination dependently inducing cleavage of lysine 48-linked TAB2 ubiquitination, USP15 also DUB independently inhibited lysosome-associated TAB2 degradation, thus enhanced TAB2 stabilization. For TAB3, USP15 inhibited NBR1-mediated selective autophagic TAB3 degradation independent of its deubiquitinating activity. Together, our results reveal a novel USP15-mediated mechanism through which efficient NF-κB activation is achieved by differentially maintaining the TAB2/3 stability.

Hydrogen sulfide pretreatment improves mitochondrial function in myocardial hypertrophy via a SIRT3-dependent manner.

BACKGROUND AND PURPOSE: Hydrogen sulfide (H2 S) is a gaseous signal molecule with antioxidative properties. Sirtuin 3 (SIRT3) is closely associated with mitochondrial function and oxidative stress. The study was to investigate whether and how H2 S improved myocardial hypertrophy via a SIRT3-dependent manner. EXPERIMENTAL APPROACH: Neonatal rat cardiomyocytes were pretreated with NaHS (50 µM) for 4 h followed by angiotensin II (Ang II, 100 nM) for 24 h. SIRT3 was silenced with siRNA technology. SIRT3 promoter activity and expression, cell surface, hypertrophic gene mRNA expression, mitochondrial oxygen consumption rate and membrane potential were measured. Male 129S1/SvImJ [wild-type (WT)] and SIRT3 knockout (KO) mice were injected with NaHS (50 µmol·kg-1 ·day-1 ; i.p.) followed by transverse aortic constriction (TAC). Echocardiography, heart mass, mitochondrial ultrastructure, volume and number, oxidative stress, mitochondria fusion and fission-related protein expression were measured. KEY RESULTS: In vitro, NaHS increased SIRT3 promoter activity and SIRT3 expression in Ang II-induced cardiomyocyte hypertrophy. SIRT3 silencing abolished the ability of NaHS to reverse the Ang II-induced cardiomyocyte hypertrophy, mitochondrial function impairment and permeability potential dysfunction, along with the decline in FOXO3a and SOD2 expression. In vivo, after TAC. NaHS attenuated myocardial hypertrophy, inhibited oxidative stress, improved mitochondrial ultrastructure, suppressed mitochondrial volume but increased mitochondrial numbers, enhanced OPA1, MFN1 and MFN2 expression but suppressed DRP1 and FIS1 expression in WT mice but not in SIRT3 KO mice CONCLUSION AND IMPLICATIONS: NaHS improved mitochondrial function and inhibited oxidative stress in myocardial hypertrophy in a SIRT3-dependent manner. LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation related to inhibitory of oxidative stress.

Dihydromyricetin (DMY) is one of the most important flavonoids in vine tea, which showed several pharmacological effects. However, information about the potential role of DMY on angiotensin II (Ang II) induced cardiac fibroblasts proliferation remains unknown. In the present study, cardiac fibroblasts isolated from neonatal Sprague-Dawley rats were pretreated with different concentrations of DMY (0-320µM) for 4h, or DMY (80µM) for different time (0-24h), followed by Ang II (100nM) stimulation for 24h, Then number of cardiac fibroblasts and content of hydroxyproline was measured. The level of cellular reactive oxygen species, malondialdehyde (MDA), activity of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were also evaluated. Expression of type I, type III collagen, α-smooth muscle actin (α-SMA), p22phox (one vital subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase), SOD and thioredoxin (Trx) were detected with real time PCR or/and western blot. We found that pre-incubation with DMY (20µM, 40µM, 80µM) for 4h, 12h or 24h attenuated the proliferation of cardiac fibroblasts induced by Ang II. Expression of type I and type III collagen, as well as α-SMA were inhibited by DMY at both mRNA and protein level. DMY also significantly decreased cellular reactive oxygen species production and MDA level, while increased the SOD activity and T-AOC. DMY suppressed p22phox, while enhanced antioxidant SOD and Trx expression in Ang II stimulated cardiac fibroblasts. Thus, dihydromyricetin attenuated Ang II induced cardiac fibroblasts proliferation related to inhibitory of oxidative stress.

Immobilization of sulfur in microgels for lithium-sulfur battery.

Immobilization of sulfur in microgels is achieved via free radical polymerization of commercial poly(ethylene glycol) dimethacrylate in the solution of sulfur-terminated poly(3-oligo(ethylene oxide)4-thiophene), a copolymer prepared by the inverse vulcanization of S8 with allyl-terminated poly(3-oligo(ethylene oxide)4-thiophene). This microgelation leads to enhanced Li-S battery performance over the sulfur-terminated polymer.