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Abstract Background Obesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice. Methods Female mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues. Results In comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice. Conclusion Sesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2’s novel role as a regulator of obesity in female mice.

BackgroundThis review systematically evaluates the efficacy and safety of the combined treatment of glucocorticoids (GC) and cyclophosphamide (CTX) in patients with membranous nephropathy (MN).MethodsAs of June 2024, a comprehensive literature search was performed utilizing several reputable databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang. A meta-analysis was then carried out using Review Manager 5.4 and STATA/SE-15 software.ResultsThis research evaluated a total of 22 articles involving 1,971 patients. The findings revealed that patients with MN receiving combined GC and CTX therapy had significantly higher complete remission rates (odds ratio = 1.78, p = 0.02) and total remission rates (odds ratio = 2.14, p = 0.01) when the follow-up period exceeded 12 months. Additionally, this treatment demonstrated greater efficacy in lowering serum creatinine levels compared to the control group (standardized mean difference = −0.19, p = 0.04), while its relapse rate was also lower than that of the control group (odds ratio = 0.51, p = 0.009). However, it has a high incidence of serious adverse effects (odds ratio = 2.32, p = 0.03).ConclusionOur systematic review highlights that the combination of GC and CTX demonstrates superior long-term effectiveness and reduced relapse rates in managing membranous nephropathy (MN). Furthermore, this drug combination is considered the optimal choice for normalizing serum creatinine levels. Data on the effectiveness and safety of glucocorticoids alone versus other drugs alone, and the treatment of secondary membranous nephropathy (SMN), are limited.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=566477, identifier CRD42024566477.

Abstract Background The anti-aging protein Klotho has diverse functions in antioxidative stress and energy metabolism through several pathways. While it has been reported that α-Klotho is downregulated in patients with insulin resistance (IR), the association between Klotho and IR is complex and controversial. The triglyceride-glucose (TyG) index has provided a practical method for assessing IR. With this in mind, our study aimed to investigate the relationship between the TyG index and soluble α-Klotho protein levels in US populations, both with and without diabetes mellitus. Methods This cross-sectional study analyzed data from middle-aged and older participants in the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. The participants were divided into two groups based on their diabetes mellitus status: those with diabetes and those without diabetes. To evaluate the relationship between the TyG index and the concentration of the α-Klotho protein in each group, a series of survey-weighted multivariable linear regression models were employed. Furthermore, to examine the association between these two variables, multivariable-adjusted restricted cubic spline curves and subgroup analysis were generated. Results The study involved 6,439 adults aged 40 years or older, with a mean age of 57.8 ± 10.9 years. Among them, 1577 (24.5%) had diabetes mellitus. A subgroup analysis indicated that the presence of diabetes significantly affected the relationship between the TyG index and the α-Klotho level. After considering all covariables, regression analysis of the participants without diabetes revealed that the α-Klotho concentration decreased by 32.35 pg/ml (95% CI: -50.07, -14.64) with each one unit increase in TyG (p

Summary: The global burden of diseases and injuries poses complex and pressing challenges. This study analyzed 369 diseases and injuries attributed to 84 risk factors globally from 1990 to 2019, projecting trends to 2040. In 2019, global risks caused 35 million deaths. Non-communicable diseases were responsible for 8.2 million deaths, primarily from air pollution (5.5 million). Cardiovascular disease from air pollution had a high age-standardized disability-adjusted life year rate (1,073.40). Communicable, maternal, neonatal, and nutritional diseases caused 1.4 million deaths, mainly due to unsafe water and sanitation. Occupational risks resulted in 184,269 transport-related deaths. Behavioral risks caused 21.6 million deaths, with dietary factors causing 6.9 million cardiovascular deaths. Diabetes linked to sugar-sweetened beverages showed significant growth (1990–2019). Metabolic risks led to 18.6 million deaths. Projections to 2040 indicated persistent challenges, emphasizing the urgent need for targeted interventions and policies to alleviate the global burden of diseases and injuries.

Abstract Background Uremic tumoral calcinosis (UTC) is a rare complication in hemodialysis patients, whose mechanism remains incompletely understood. We report two cases with UTC who experienced completely different patterns of regression following parathyroidectomy, although there were no significant differences in serum calcium levels, parathyroid hormone, or phosphorus production between the two patients. Case presentation Case 1 had a substantial improvement in soft tissue calcification. However, in Case 2, one calcified mass was partially absorbed, while the others were aggravated with severe microvascular calcification and subcutaneous extravascular calcification. Whole-exome sequencing data revealed five mutation sites associated with atherosclerosis. Conclusion The different outcomes in UTC patients after PTX are rare. Further studies are required to elucidate the mechanism of paradoxical changes occurring in patients with UTC after parathyroidectomy.

ObjectiveTo observe the feasibility of shear wave elastography (SWE) in the diagnosis of peripheral neuropathy in patients undergoing hemodialysis [chronic kidney disease stage 5 dialysis (CKD5D)].MethodsForty patients with CKD5D were divided into a uremic peripheral neuropathy (UPN) group (n = 25) and a non-UPN group (n = 15) according to the results of a neuro-electrophysiological examination. Sixteen healthy control subjects were also enrolled in this study. Two-dimensional ultrasound examination was conducted, and SWE was then performed to measure Young’s modulus of the tibial nerve. The left and right diameters (D1), anterior and posterior diameters (D2), perimeter (C), cross-sectional area (CSA), and Young’s modulus (E) were measured three times at the same non-entrapment site. The average values were recorded and calculated. The following evaluation indices were also analyzed: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC).ResultsD1, D2, C, and CSA were not significantly different among the three groups (P > 0.05). However, the difference in the E value among the three groups was statistically significant (P < 0.05). The AUC was 0.889 based on the E value. Using a tibial nerve E value of 48.35 kPa as the cutoff value, the sensitivity, specificity, PPV, and NPV were 86.0%, 84.0%, 81.1%, and 88.1%, respectively.ConclusionsSWE is useful for the diagnosis of peripheral neuropathy in patients with CKD5D. Young’s modulus of 48.35 kPa for the tibial nerve is the optimal cutoff value and has the best diagnostic efficiency for peripheral neuropathy in CKD5D patients.

A microwave photonic phase shifter that can realize a full 360-deg phase shift is presented. In the scheme, an optical polarization modulator is used to generate a single-sideband optical microwave signal with two orthogonally polarized tones, then a polarization sensitive electro-optical phase modulator is used to introduce the relative phase shifts between the two orthogonally polarized tones to realize the desired phase shift for the microwave signal in the photocurrent, and the phase shift of the microwave signal increases linearly with the DC driving voltage while it keeps a constant amplitude. The simulation results show that continuous phase shift with tuning range from -180 deg to +180 deg is realized for the microwave with the frequency from 4 to 38 GHz and the amplitude variation of the phase-shifted microwave signal is <1 dB. [ABSTRACT FROM AUTHOR]

Purpose: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) are an inhibitor of receptor tyrosine kinases (RTKs) that was discovered in recent years, and many studies showed that LRIG1 is a tumor suppressor gene and may be related to tumor drug resistance. In this study, we explored whether LRIG1 protein expression can improve the chemosensitivity of glioma cells and what was its mechanism. Materials and Methods: We collected 93 cases of glioma tissues and detected the expression of LRIG1 and BCL-2. We constructed a multidrug resistance cell line U251/multidrug resistance (MDR) and examined the change of LRIG1 and BCL-2 at mRNA and protein expression levels. LRIG1 expression was upregulated in U251/MDR cells and we detected the change of multidrug resistance. Meanwhile, we changed the expression of LRIG1 and BCL-2 and explored the relationship between LRIG1 and BCL-2. Finally, we also explored the relationship between LRIG1 and RTKs. Results: LRIG1 was negatively correlated with BCL-2 expression in glioma tissue and U251/MDR cells, and upregulation of LRIG1 can enhance chemosensitivity and inhibit BCL- 2 expression. Furthermore, LRIG1 was negatively correlated with RTKs in U251/MDR cells. Conclusion: These results demonstrated that LRIG1 can improve chemosensitivity by modulating BCL-2 expression and RTK signaling in glioma cells. [ABSTRACT FROM AUTHOR]

Purpose: Cancer stem cells have recently been thought to be closely related to tumor development and reoccurrence. It may be a promising way to cure malignant glioma by using glioma stem cell-targeted dendritic cells as a tumor vaccine. In this study, we explored whether pulsing dendritic cells with antigens of glioma stem cells was a potent way to induce specific cytotoxic T lymphocytes and anti-tumor immunity. Materials and Methods: Cancer stem cells were cultured from glioma cell line U251. Lysate of glioma stem cells was obtained by the repeated freezing and thawing method. Dendritic cells (DCs) were induced and cultured from the murine bone marrow cells, the biological characteristics were detected by electron microscope and flow cytometry. The DC vaccine was obtained by mixing DCs with lysate of glioma stem cells. The DC vaccine was charactirizated through the mixed lymphocyte responses and cell killing experiment in vitro. Level of interferon-γ (IFN-γ) in the supernatant was checked by ELISA. Results: After stimulation of lysate of glioma stem cell, expression of surface molecules of DC was up-regulated, including CD80, CD86, CD11C and MHC-II. DCs pulsed with lysate of glioma stem cells were more effective than the control group in stimulating original glioma cells-specific cytotoxic T lymphocytes responses, killing glioma cells and boosting the secretion of IFN-γ in vitro. Conclusion: The results demonstrated DCs loaded with antigens derived from glioma stem cells can effectively stimulate naive T cells to form specific cytotoxic T cells, kill glioma cells cultured in vitro. [ABSTRACT FROM AUTHOR]

The article presents a study which explained the relationship of Leucine-rich repeats and immnoglobulin-like domains 1 (LRlG1), an anti-oncogene, with Bcl-2 and manganese superoxide dismutase (MnSOD) in glioma. The researchers created a transfected cell line with increased LRlG1 expression. They found that LRlG1 expression is related to Bcl-2 and MnSOD expression in glioma. They concluded that LRlG1 can improve the chemosensitivity of glioma.