No abstract

BackgroundFatty acid deposition in the liver can activate a number of pro-inflammatory signaling pathways such as the Toll-like receptor 4 (TLR4) pathway, which may be important in the pathogenesis of nonalcoholic steatohepatitis. 1,25(OH)2D3 downregulates the expression of TLR4 and may represent a novel treatment strategy for reducing hepatocyte injury. Therefore, in this study, we investigated the protective effects of 1,25(OH)2D3 on diabetic liver injury in vivo.MethodsStreptozotocin (STZ)-induced diabetic rats were randomly divided into five groups and treated with low-dose 1,25(OH)2D3 (0.025 μg/kg/day), medium-dose 1,25(OH)2D3 (0.15 μg/kg/day), high-dose 1,25(OH)2D3 (0.3 μg/kg/day), insulin (protamine zinc insulin 16 U/kg/day, subcutaneous injection), or no intervention (the control group). Sixteen weeks later, the rats were killed, and blood samples were obtained to test lipid profiles and hepatic function. The infiltration of inflammatory cells, the level of fibrosis, and the expression levels of TLR4, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-α (TNF-α) in the liver were analyzed. The hepatocytes were treated with vehicle control, LPS (100 ng), high fat [DMEM + FFA (0.1 mM: palmitic acid, oleic acid, 1:2)], LPS + high fat, vehicle + 1,25(OH)2D3 (10−7 M), LPS + 1,25(OH)2D3, high fat + 1,25(OH)2D3, or LPS + high fat + 1,25(OH)2D3. RNA and protein were extracted to detect the expression of TLR4 and downstream inflammatory factors such as NF-ΚB, TNF-α, and IL-6. Groups of data were compared by single factor variance analysis.ResultsHigh-dose 1,25(OH)2D3 administration for 16 weeks downregulated the expression of TLR4, NF-κB, and TNF-α in the liver tissue of diabetic rats and attenuated hepatic inflammation and fibrosis, as shown by immunohistochemical staining, hematoxylin and eosin staining, Masson’s trichrome staining, reverse transcription polymerase chain reaction (RT-PCR), and western blotting. In vitro, hepatocytes treated with high fat or LPS exhibited significantly increased expression of TLR4, NF-κB, and downstream inflammatory factors (P < 0.05). Intervention with 1,25(OH)2D3 decreased the expression of TLR4, NF-κB, and inflammatory factors (P < 0.05).Conclusions1,25(OH)2D3 exhibited protective effects against diabetes-related liver injury, possibly through downregulation of components of the TLR4 signaling pathway.

BackgroundSyndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in hospitalized patients and is often described in patients with small-cell carcinoma of the lung. In this report, we described both Castleman’s disease and lymphoma coexisting in one patient with SIADH.Case presentationA 70-year-old Chinese woman with a history of diabetes mellitus and insulin therapy had severe hyponatremia and gastrointestinal symptoms. Through a series of examinations, common causes such as pulmonary carcinoma were excluded. An abdominal mass was detected by computed tomography. Although the peripheral lymph node biopsy showed the pathological result as Castleman’s disease, the pathology of the abdominal lymph node revealed diffuse large B-cell lymphoma. After chemotherapy, the hyponatremia was treated during a period of follow-up.ConclusionThis patient presented with the rare clinical condition of inappropriate antidiuretic hormone secretion alongside Castleman’s disease and lymphoma. Asymptomatic hyponatremia may persist for some time suggesting that clinical physicians should pay attention to the mild cases of hyponatremia. We also hypothesized that Castleman’s disease is a condition of pre-lymphoma with both having the ability to cause SIADH. The possibility of lymphoma as well as Castleman’s disease triggering the development of SIADH should also be taken into consideration for conducting recurrent biopsies.