BACKGROUND: Heavy metals are significant risk factors for kidney function. Numerous studies have shown that exposure to heavy metals negatively correlates with kidney function through oxidative stress pathways, and serum α-klotho is linked to oxidative stress. However, the role of α-klotho in the relationship between blood lead, mercury, and kidney function remains unclear. METHOD: This study evaluated the mediating role of alpha-klotho in the relationship between lead, mercury and renal function, using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) in U.S. adults aged 40-79. The sample included 11,032 participants, with blood lead, mercury, α-klotho, and other relevant covariates measured. Inductively coupled plasma mass spectrometry was used to assess blood lead and mercury levels, and enzyme-linked immunosorbent assay (ELISA) was employed to measure serum α-klotho. Kidney function was evaluated using estimated glomerular filtration rate (eGFR) based on creatinine levels. Multivariable linear regression was conducted to analyze the relationships between blood lead, mercury, α-klotho, and eGFR. A mediation analysis model was used to assess whether α-klotho influenced these associations. RESULTS: We observed a significant association between blood lead and eGFR. Mediation analysis revealed that α-klotho accounted for 12.76% of the relationship between serum lead and eGFR in the NHANES population. Subgroup analysis showed that α-klotho mediated 12.43%, 6.87%, 21.50% and 5.44% of the relationship between blood lead and eGFR in women, middle-aged adults (40-59 years old), without cardiovascular disease and hypertension, respectively. However, α-klotho did not mediate the relationship between blood mercury and eGFR in terms of gender or age. This newly identified pathway may provide valuable insights for the prevention and treatment mechanisms related to kidney function impairment. CONCLUSION We found that blood lead was associated with renal function. According to the results of subgroup analysis, for blood lead, serum α-klotho mediated the association in females, middle aged 60-79 years. The relationship between blood mercury and renal function was not clinically significant, and serum α-Klotho mediated the relationship between blood mercury and renal function without significant clinical significance.
Humans ; Middle Aged ; Lead/blood* ; Female ; Klotho Proteins ; Male ; Aged ; Adult ; Mercury/blood* ; Glomerular Filtration Rate ; Nutrition Surveys ; United States ; Kidney/physiology* ; Glucuronidase/blood* ; Environmental Pollutants/blood*

ObjectiveTo evaluate the efficacy and safety of Qingyusan capsules in the long-term treatment of mild to moderate active ulcerative colitis （UC） with the syndrome of large intestine dampness-heat. MethodA randomized， controlled design was adopted， and 88 patients with mild to moderate UC and syndrome of large intestine dampness-heat were randomized into a Qingyusan （Qingyusan capsules， 0.8 g·d^-1） group and a control （mesalazine， 0.4 g·d^-1） group， with 44 patients in each group. Three and one patients dropped out in the control and Qingyusan groups， respectively， during the 32 weeks of treatment. The clinical remission rate， mucosal healing rate， and modified Mayo score， TCM symptom score， and short inflammatory bowel disease questionnaire （SIBDQ） score before and after treatment were compared between the two groups. The colonoscopic and pathological changes were observed， and the clinical safety was compared between the two groups. ResultAfter treatment， the clinical remission rate and mucosal healing rate in the Qingyusan group were 72.1% （31/43） and 74.4% （32/43）， respectively， which were higher than those ［26.8% （11/41） and 41.5% （17/41）， respectively］ in the control group （χ²=17.200， χ²=10.843， respectively， both P<0.01）. The treatment in both groups decreased the modified Mayo score， partial Mayo score， and TCM symptom score （P<0.05）， and the decreases in the Qingyusan group were higher than those in the control group （P<0.01）. After treatment， the SIBDQ scores in both groups increased （P<0.05）， and the increase was more pronounced in the Qingyusan group than in the control group （P<0.01）. There was no difference in the incidence of adverse events between the two groups. ConclusionThe clinical efficacy of Qingyusan capsules is remarkable in the long-term treatment of UC with the syndrome of large intestine dampness-heat. Particularly， Qingyusan capsules demonstrates advantages in inducing and maintaining clinical remission， promoting mucosal healing， alleviating TCM symptoms， and enhancing the survival quality of patients， with high safety.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t _1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.

Objective:To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice.Methods:A total of 80 C57BL/6 mice were randomly divided into the control group, resveratrol (Res) group, radiation (RT) group and radiation+resveratrol (RT+Res) group. In the RT group, mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months. Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation. The hearts of mice were collected for HE staining, immunofluorescence, TUNEL staining, Masson staining and Western blot to evaluate the expression of silent information regulator 1 (SIRT1), the level of oxidative stress, inflammatory response, apoptosis and the degree of fibrosis in myocardial tissues. Experimental data were expressed as Mean ± SD. Continous data were statistically analyzed by t-test. Results:After 3 months of irradiation, compared with the control group, the ejection fraction (EF) and fractional shortening (FS) of cardiac function were decreased, and myocardial degeneration and disorder, reactive oxygen species (ROS) and inflammatory levels (interleukin-1β, interleukin-6, tumor necrosis factor-α), myocardial apoptosis (TUNEL positive cell rate) and fibrosis were increased in the RT group. In the RT+Res group, the cardiac function was improved, the expression of SIRT1 was increased, and the levels of oxidative stress, inflammation, myocardial apoptosis and fibrosis were decreased.Conclusions:Resveratrol can reduce oxidative stress, inflammatory infiltration, apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury, thereby improving cardiac structural abnormalities and cardiac dysfunction. This protective effect can be mediated by upregulation of SIRT1 expression.

Objective:To observe the expression of sirtuin 3 (Sirt3) and mitochondrial damage-associated proteins in lipopolysaccharide (LPS)-induced acute kidney injury mouse model and renal tubular epithelial cells, and to explore the role of Sirt3 in LPS-induced abnormal mitochondrial dynamics in renal tubular epithelial cells.Methods:Eighteen specific pathogen free (SPF) male C57BL/6 mice were randomly assigned to control group, LPS 24 h group and LPS 48 h group. The control group was intraperitoneally injected with physiological saline (0.1 ml/10 g), and LPS 24 h group and LPS 48 h group were intraperitoneally injected with LPS (10 mg/kg) solution. Renal functional indexes of mice were analyzed by automatic biochemical analyzer. The pathological change of the kidney was observed by HE staining, and the expressions of dynamin-related protein-1 (Drp1), optic atrophy type 1 (Opa1) and Sirt3 were evaluated by Western blotting. Expression and distribution of Sirt3 in kidney was assessed by immunohistochemistry. Human renal tubular epithelial cells (HK-2) were exposed to 10 μg/ml LPS for 24 h, and the expression of Drp1, Opa1 and Sirt3 were detected by Western blotting. Cell apoptosis was assessed by Hoechst-33342 staining. After transfection to HK-2 cells with pcDNA3.1-Sirt3 recombinant plasmid, the expressions of Sirt3, Drp1, Opa1 and cell apoptosis were detected by the same methods as above.Results:(1) The levels of blood urea nitrogen and serum creatinine in LPS group were significantly higher than those in control group (both P<0.05), and the pathological changes of kidney were obvious. (2) Compared with the control group, the expression of mitochondrial fission-associated protein Drp1 in renal tissue of LPS group was significantly higher ( P<0.05), and the expression of mitochondrial fusion associated protein Opa1 was significantly lower ( P<0.05). (3) Compared with the control group, the expression of Sirt3 in LPS group was significantly lower ( P<0.05), and immunohistochemistry results showed that Sirt3 was mainly expressed in glomerular vascular endothelial cells and renal tubular epithelial cells. (4) In vitro, LPS stimulation induced increased Drp1 expression in HK-2 cells ( P<0.05), decreased Opa1 and Sirt3 expression (both P<0.05), and increased apoptosis ( P<0.05). (5) LPS-induced mitochondrial dynamics disturbance and apoptosis were alleviated by pcDNA3.1-Sirt3 recombinant plasmid transfection. Conclusions:LPS can induce down-regulation of Sirt3 expression and disturbance of mitochondrial dynamics, and Sirt3 may play a protective role in LPS-induced acute kidney injury by regulating mitochondrial dynamics.

Objective To evaluate the value of three-dimensional ultrasound volume contrast imaging (VCI) and tomo graphy ultrasound imaging (TUI) techniques in observing fetal spinal conus medullaris (CM) position and lumbar enlargement of spinal cord morphologic changes,for assessment of tethered cord (TC).Methods Totally 17 abnormal fetuses of spinal diseases combined with TC (abnormal group) were examined by three dimensional ultrasound VCI and TUI techniques.The position of CM was recorded,and the transverse and anteroposterior diameters of lumbar enlargement of spinal cord were measured and compared with 300 cases of normal fetuses (normal group).Results As the growth of the gestational age (CA),CM terminal position increased.All the ends of CM located at L3 or L3 above level in normal.The transverse and anteroposterior diameters of lumbar enlargement in normal group showed good linear relationship with GA.Transverse diameter (mm) =0.677+0.147 ×GA (R2 =0.836,P＜0.05),anteroposterior diameter (mm)-0.994+ 0.152× GA (R2=0.894,P＜0.05).Compared with the corresponding GA fetuses in normal group,the anteroposterior diameter of lumbar enlargement decreased in abnormal group (P=0.002),while no statistical difference of the transverse diameter was found between the two groups (P=0.082).Conclusion Position of CM and lumbar enlargement measure ment can provide valuable reference information for clinical prenatal diagnosis of fetal spinal TC.