PURPOSE: Deposition of polymeric IgA1 in the kidney mesangium is the hallmark of IgA nephropathy, but the molecular mechanisms of IgA-mediated mesangial responses and inflammatory injuries remain poorly understood. We hypothesize that Toll-like receptor 4 (TLR4) is involved in IgA-induced mesangial cell activation. MATERIALS AND METHODS: Mouse mesangial cells were stimulated with lipopolysaccharide (LPS) (1 microg/mL), IgA (20 microg/mL), or both, and TLR4 expression was measured by real time RT-PCR and Western blot. Intracellular responses to LPS or IgA were assessed by Western blot for ERK1/2, JNK, p38 MAP kinases (MAPKs), Ikappa-Balpha degradation and fibronectin secretion. MCP-1 secretion was assessed by ELISA. Small interfering RNA (siRNA) of TLR4 was used to confirm that the effects were caused by TLR4 activity. RESULTS: LPS- or IgA-treatment upregulated the levels of TLR4 mRNA and protein in cultured MMC at 24 h. LPS and IgA induced rapid phosphorylation of MAPKs, but degradation of Ikappa-Balpha was observed only in LPS-treated MMC. LPS, but not IgA, induced increased secretion of MCP-1 and fibronectin at 24 h or 48 h. Combined LPS and IgA treatment did not cause additional increases in TLR4 mRNA and protein levels or Ikappa-Balpha degradation, and MCP-1 and fibronectin secretions were less than with LPS alone. LPS- or IgA-induced TLR4 protein levels and MAPK activation were inhibited by transfection with TLR4 siRNA. CONCLUSION: These results indicate that the activation of MAPKs and MCP-1 secretion are mediated by TLR4, at least in part, in IgA-treated mesangial cells. TLR4 is involved in mesangial cell injury by induction of pro-inflammatory cytokines in IgA nephropathy.
Animals ; Chemokine CCL2/secretion ; Enzyme-Linked Immunosorbent Assay ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibronectins/secretion ; Glomerulonephritis, IGA/*metabolism ; I-kappa B Proteins/metabolism ; Mesangial Cells/*metabolism/secretion ; Mice ; Mice, Transgenic ; Phosphorylation ; RNA Interference ; RNA, Messenger/metabolism ; *Signal Transduction ; Toll-Like Receptor 4/antagonists & inhibitors/genetics/*metabolism

Pelvic actinomycosis is an uncommon infectious disease. It induces a chronic, suppurative illness characterized by an infiltrative and granulomatous response and, thus, the clinical and radiologic findings may mimic other inflammatory and neoplastic conditions. A 56-year-old female with a long-standing intrauterine device was diagnosed with pelvic actinomycosis manifesting as a large uterine mass with locally infiltrative spread into surrounding tissue that mimicked uterine malignancy. Actinomyces israelii infection was confirmed with a surgical specimen, and the patient was treated with antibiotic medication. Pelvic actinomycosis must be included in the differential diagnoses of patients with an infiltrative pelvic mass extending across tissue planes or in patients with findings of multiple microabscesses, particularly in a patient with an intrauterine device, even the lesion primarily involves the uterus.
Actinomyces ; Actinomycosis ; Communicable Diseases ; Diagnosis, Differential ; Female ; Humans ; Intrauterine Devices ; Middle Aged ; Pelvic Inflammatory Disease ; Uterus

Background: As the population rapidly ages, older adults are increasingly likely to experience mobility problems. This study aims to explore the characteristics related to an elderly person’s willingness to live in a nursing home if they have mobility problems Methods: This study analyzed data from 9,917 older adults (5,976 young-old and 3,941 old-old) obtained from the 2020 National Survey of Older Koreans. The dependent variable was the intended place of residence for older adults with mobility problems.Independent variables included various characteristics: (1) sociodemographic and social support, (2) health and functional status, and (3) residential environment. Rao-Scott chi-square tests and survey logistic regression analyses were performed for the young-old and old-old, respectively. Results: The intention to live in a nursing home was significantly different between the young-old (30.4%) and the old-old (34.7%) (p=0.009). According to fully adjusted multivariable analyses, for the young-old, the odds ratio of intending to live in a nursing home was significantly higher in social security benefit recipients (1.45; 95% confidence interval [CI], 1.06–1.97) compared to other individuals. The odds ratio was higher in unmarried (divorced, separated, widowed, or never-married) individuals for both young-old (1.41; 95% CI, 1.22–1.63) and old-old (1.34; 95% CI, 1.09–1.65) age groups, compared to their respective married counterparts. Conclusion The results of this study suggest that in an aging society, health and social policies should be designed considering the different characteristics of the elderly to improve their health, function, and quality of life.

Metastasis from extramammary malignancy to the breast is rare, and metastasis of cervical cancer to the breast is quite uncommon. We report atypical sonographic findings of a rapid growing, single, and circumscribed mass with complex cystic and solid echo pattern in a 50-year-old female. The mass confirmed a metastasis from cervical cancer. It is rare, but the possibility of breast metastasis should be considered when a rapidly growing breast mass is located in between the parenchyma and subcutaneous fat layer.

Background and Objectives: Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. Methods: Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. Results: One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups. Conclusions Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.

Background and Objectives: Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. Methods: Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. Results: One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups. Conclusions Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.