Malignant glioma is a fatal brain tumor whose pathological progression is closely associated with glycolytic reprogramming, leading to the high expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein, cluster of differentiation 147 (CD147) for enhancing lactate efflux. In particular, malignant glioma cells (GMs) release tremendous number of exosomes, nanovesicles of 30 to 200 nm in size, promoting tumor progression by the transport of pro-oncogenic molecules to neighboring cells. In the present study, we found that hypoxia-induced malignant GMs strongly enhanced MCT1 and CD147 expression, playing a crucial role in promoting calcium-dependent exosome release. Furthermore, it was first identified that hypoxic GMs-derived exosomes contained significantly high levels of MCT1 and CD147, which could be quantitatively detected by noninvasive localized surface plasmon resonance and atomic force microscopy biosensors, demonstrating that they could be precise surrogate biomarkers for tracking parent GMs’ metabolic reprogramming and malignant progression as liquid biopsies.
Background and Objective Periodontitis is a serious disease that affects the majority of adult population around the world. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this dreadful disease. In this study, we utilized adeno-associated virus (AAV) expressing Cathepsin K (Ctsk) shRNA (AAV-sh-Ctsk) to silence Ctsk in vivo and subsequently evaluated its impact in periodontitis as a potential therapeutic strategy for this disease. Material and Methods We used a known mouse model of periodontitis, in which wild-type BALB/cJ mice were infected with Porphyromonas gingivalis W50 (P. gingivalis) in the maxillary and mandibular periodontium to induce the disease. AAV-sh-Ctsk was then administrated locally into the periodontal tissues in vivo, followed by analyses to assess the progression of the disease. Results AAV-mediated Ctsk silencing drastically protected mice (>80%) from P. gingivalis-induced bone resorption by osteoclasts. Also, AAV-sh-Ctsk administration drastically reduced inflammation by impacting the expression of many inflammatory cytokines as well as T cell and dendritic cell numbers in periodontal lesions. Conclusion AAV-mediated Ctsk silencing can simultaneously target both the inflammation and bone resorption associated with periodontitis through its inhibitory effect on immune cells and osteoclast function. Thereby, AAV-sh-Ctsk administration can efficiently protect against periodontal tissue damage and alveolar bone loss, establishing this AAV-mediated local silencing of Ctsk as an important therapeutic strategy for potently treating periodontal disease.
In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb) = 105 g/L] were randomly assigned to 4 groups, all receiving 60 mg/d iron and 400 mug/d folic acid. The iron+folic acid (IF) group (n = 93) served as reference, the iron+folic acid+retinol group (IFA) (n = 91) was treated with 2000 mug retinol, the iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4 groups (P < 0.001). The increase in the IFAB group was 5.4 +/- 1.1 g/L greater than in the IF group (P < 0.001). The reduced prevalence of anemia (Hb < 110g/L) and ID anemia were significantly greater in the groups supplemented with retinol and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were less prevalent in the IFA group than in the IF group (P < 0.05) and improved well-being was more prevalent in the groups receiving additional retinol and/or riboflavin than in the IF group (P < 0.05). Thus, a combination of iron, folic acid, retinol, and riboflavin was more effective than iron plus folic acid alone. Multimicronutrient supplementation may be worthwhile for pregnant women in rural China.
Aims: Our previous work has shown that lymphocytes synthesize and secrete catecholamines (CAs), which regulate lymphocyte proliferation and apoptosis. In the present study, we explored the effect of the lymphocyte-derived CAs on differentiation and function of T helper (Th) cells. Methods: Lymphocytes were separated from the mesenteric lymph nodes of mice and stimulated by concanavalin A (Con A). These cells were treated with alpha-methyl-p- tyrosine (α-MT), an inhibitor of tyrosine hydroxylase (TH) that is a rate-limiting enzyme for synthesis of CAs, and pargyline, an inhibitor of monoamine oxidase that degrades CAs. Results: Treatment of Con A-stimulated lymphocytes with α-MT (10–6
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