Increased Circulating IL-32 Is Associated With Placenta Macrophage-derived IL-32 and Gestational Diabetes Mellitus.

OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.

Molecular mechanisms and functions of pyroptosis in sepsis and sepsis-associated organ dysfunction.

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death in intensive care units. The development of sepsis-associated organ dysfunction (SAOD) poses a threat to the survival of patients with sepsis. Unfortunately, the pathogenesis of sepsis and SAOD is complicated, multifactorial, and has not been completely clarified. Recently, numerous studies have demonstrated that pyroptosis, which is characterized by inflammasome and caspase activation and cell membrane pore formation, is involved in sepsis. Unlike apoptosis, pyroptosis is a pro-inflammatory form of programmed cell death that participates in the regulation of immunity and inflammation. Related studies have shown that in sepsis, moderate pyroptosis promotes the clearance of pathogens, whereas the excessive activation of pyroptosis leads to host immune response disorders and SAOD. Additionally, transcription factors, non-coding RNAs, epigenetic modifications and post-translational modifications can directly or indirectly regulate pyroptosis-related molecules. Pyroptosis also interacts with autophagy, apoptosis, NETosis, and necroptosis. This review summarizes the roles and regulatory mechanisms of pyroptosis in sepsis and SAOD. As our understanding of the functions of pyroptosis improves, the development of new diagnostic biomarkers and targeted therapies associated with pyroptosis to improve clinical outcomes appears promising in the future.

[The influence of the different components of nourishing kidney herbs on osteoporosis rats].

OBJECTIVE: To observe the influent of the different components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with Dexamethasona(DXM). METHOD: Models of three-month old SD female rats with osteoporosis here made by being fed with low calcium diet (containing calcium 0.2%) and distilled water, and injected with DXM 0.1 mg/100 g weight intramuscularly, twice a week. Then the osteoporosis rats were treated with different components of nourishing kidney herbs, and the change of calcium, phosphate, alkaline phosphatase(ALP), calcitonin(CT), PTH, CT/PTH, estrogen(E2), testosterone(T), T/E2 and bone section and bone quantitative morphology in these osteoporosis rats were observed. RESULT: The total components of nourishing kidney herbs could improve the general condition of osteoporosis rats, decrease PTH, increase CT, estrogen, testosterone, CT/PTH and T/E2. The total components of nourishing kidney herbs could improve osteoporotic state, promote bone formation, and inhibite bone resorption. But no effect of the A, B, C, D components of nourishing kidney herbs on the main items of bone metabolism in osteoporosis rats induced with DXM was found. CONCLUSION: It is possible that the purification and separation of these herbs weaken or destroy the integrative effect of nourishing kidney herbs or destroy effective components of nourishing kidney herbs during the process of purification and separation.

[Effects of genistein on proliferation and differentiation of cultured osteoblasts in vitro].

OBJECTIVE: To study the effects of genistein on proliferation and differentiation of cultured osteoblasts in vitro. METHODS: MTT and PNPP were used separately to observe the proliferation and the activity of ALP of osteoblasts cultured in vitro with different concentration genistein for different incubation periods. Protein was measured by Lowry method. RESULTS: It was found that genistein had the effects on promoting proliferation of osteoblasts cultured for 24 h and 48 h at concentration ranging from 1 x 10(-9) mol/L to 1 x 0(-5) mol/L. The activity of ALP was stimulated by genistein at concentration ranging from 1 x 10(-7) mol/L to 1 x 10(-5) mol/L after 72 h incubation. CONCLUSION: Genistein has the effects on stimulating the proliferation and differentiation of cultured osteoblasts in vitro.