Effect of hyperbaric oxygen combined with folic acid on clinical efficacy and cognitive function in patients with cerebral small vessel disease.

OBJECTIVE: To identify the effect of hyperbaric oxygen combined with folic acid on clinical efficacy and cognitive function in patients with cerebral small vessel disease (CSVD), and to analyze the risk factors affecting efficacy. METHODS: Data from 108 elderly patients with CSVD (homocysteine (Hcy) > 10 µmol/L) treated in The First Hospital of Yulin from February 2019 to February 2022 were retrospectively analyzed. Among them, 50 patients treated with folic acid were set as the control group (CG), and the remaining 58 patients treated with additional hyperbaric oxygen therapy were in the study group (SG). Clinical efficacy was compared between the two groups after treatment, and changes in Hcy level before and after treatment were observed. Montreal Cognitive Assessment (MoCA) was used to compare the improvement of cognitive function between two groups. According to the efficacy after treatment, patients with markedly effective and effective responses were set as the improved group, and patients with ineffective response as the unimproved group. Risk factors affecting the efficacy of the patients were analyzed by logistic regression. Also, changes in quality of life (assessed by activities of daily living (ADL) scale) before and after treatment as well as the incidence of adverse reactions after treatment were and compared between groups. RESULTS: Before treatment, there was no significant difference identified in MoCA scores, plasma Hcy levels, or ADL scores between the two groups (P > 0.05). After treatment, scores of MoCA and ADL increased and plasma Hcy level decreased in both groups, and the changes in the SG were more significant than those in the CG (P < 0.05). Additionally, no notable difference was observed in the incidence of adverse reactions between the two groups (P > 0.05). Logistic regression analysis revealed that hypertension, hyperlipidemia, and diabetes were risk factors affecting the efficacy. CONCLUSION: Hyperbaric oxygen combined with folic acid can effectively improve cognitive function and quality of life, and reduce Hcy level in patients with CSVD. In addition, hypertension, hyperlipidemia, and diabetes are risk factors affecting efficacy.

Presence of FOXP3(+)Treg cells is correlated with colorectal cancer progression.

The transcription factor FOXP3 is specifically expressed in regulatory T (Treg) cells and appears to mediate immune surveillance. Indeed, FOXP3(+)Treg cells have been linked to disease pathogenesis, including some cancers. This study investigated the presence of FOXP3(+)Treg cells in colorectal cancer and the relationship of FOXP3 expression with clinicopathological features of colorectal cancer. Immunohistochemistry was used to detect expression of FOXP3 in 63 samples of colorectal cancer and 20 samples of healthy colorectal tissue; flow cytometry was used to detect FOXP3(+)Treg cells in peripheral blood. FOXP3 was more commonly expressed in colorectal cancer tissues than in normal colorectal tissues (P < 0.05). Similarly, the percentage of FOXP3(+)Treg cells in the peripheral blood was higher in patients with colorectal cancer than in control individuals (P < 0.05). The expression of FOXP3 was positively correlated with gender, Dukes staging, and lymph node metastasis. Further, expression increased with the increasing degree of malignancy (P < 0.05). Thus, FOXP3 expression may represent a valuable index in evaluating the degree of malignancy, clinicopathologic staging, and lymph node metastasis in colorectal cancer. Further, detection of FOXP3(+)Treg cells may be useful in predicting invasion, metastasis, and prognosis of patients with colorectal cancer.

Curcumin regulates hepatoma cell proliferation and apoptosis through the Notch signaling pathway.

Curcumin has become a compound of interest for its antioxidant and anti-neoplastic properties. This study sought to determine the effect of curcumin administration on cell proliferation and apoptosis in hepatoma cells. SMMC-7721 hepatoma cells were treated with 10, 30, or 90 µM curcumin solution, with DMEM alone (negative control), or with 20 mg/L fluorouracil (positive control). MTT colorimetry detected significant differences in the rates of cell proliferation inhibition following curcumin treatment, with increasing inhibition accompanying increasing doses of curcumin (P < 0.05), compared to the negative control. Similarly, flow cytometry revealed significant differences in the numbers of apoptotic cells following curcumin treatment: increasing doses of curcumin produced increases in the numbers of apoptotic cells (P < 0.05). To determine whether curcumin exerts these effects by altering the Notch signaling pathway, a phenomenon reported for other cancers, relative expression of Notch1 mRNA and protein were determined in curcumin-treated cells. Both mRNA and protein expression of Notch1 decreased with increasing curcumin dose (P < 0.05). Thus, curcumin appears to inhibit proliferation and induce apoptosis in hepatoma cells by altering the Notch signaling pathway.

BMP4 enhances foam cell formation by BMPR-2/Smad1/5/8 signaling.

Atherosclerosis and its complications are characterized by lipid-laden foam cell formation. Recently, an obvious up-regulation of BMP4 was observed in atherosclerotic plaque, however, its function and the underlying mechanism remains unknown. In our study, BMP4 pretreatment induced macrophage foam cell formation. Furthermore, a dramatic increase in the ratio of cholesteryl ester (CE) to total cholesterol (TC) was observed in BMP4-treated macrophages, accompanied by the reduction of cholesterol outflow. Importantly, BMP4 stimulation inhibited the expression levels of the two most important cellular cholesterol transporters ABCA1 and ABCG1, indicating that BMP4 may induce formation of foam cells by attenuating transporters expression. Further mechanism analysis showed that BMPR-2, one of the BMP4 receptors, was significantly increased in BMP4 treated macrophage foam cells. That blocking its expression using specific siRNA significantly increased ABCA1 and ABCG1 levels. Additionally, BMP4 treatment triggered the activation of Smad1/5/8 pathway by BMPR-2 signaling. After blocking the Smad1/5/8 with its inhibitor, ABCA1 and ABCG1 expression levels were up-regulated significantly, suggesting that BMP4 inhibited the expression of ABCA1 and ABCG1 through the BMPR-2/Smad1/2/8 signaling pathway. Therefore, our results will provide a new insight about how BMP4 accelerate the progressio of atherosclerosis, and it may become a potential target against atherosclerosis and its complications.

miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease.

BACKGROUND: Atherosclerosis constitutes the leading contributor to morbidity and mortality in cardiovascular and cerebrovascular diseases. Lipid deposition and inflammatory response are the crucial triggers for the development of atherosclerosis. Recently, microRNAs (miRNAs) have drawn more attention due to their prominent function on inflammatory process and lipid accumulation in cardiovascular and cerebrovascular disease. Here, we investigated the involvement of miR-21 in lipopolysaccharide (LPS)-induced lipid accumulation and inflammatory response in macrophages. METHODS: After stimulation with the indicated times and doses of LPS, miR-21 mRNA levels were analyzed by Quantitative real-time PCR. Following transfection with miR-21 or anti-miR-21 inhibitor, lipid deposition and foam cell formation was detected by high-performance liquid chromatography (HPLC) and Oil-red O staining. Furthermore, the inflammatory cytokines interleukin 6 (IL-6) and interleukin 10 (IL-10) were evaluated by Enzyme-linked immunosorbent assay (ELISA) assay. The underlying molecular mechanism was also investigated. RESULTS: In this study, LPS induced miR-21 expression in macrophages in a time- and dose-dependent manner. Further analysis confirmed that overexpression of miR-21 by transfection with miR-21 mimics notably attenuated lipid accumulation and lipid-laden foam cell formation in LPS-stimulated macrophages, which was reversely up-regulated when silencing miR-21 expression via anti-miR-21 inhibitor transfection, indicating a reverse regulator of miR-21 in LPS-induced foam cell formation. Further mechanism assays suggested that miR-21 regulated lipid accumulation by Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) pathway as pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-κB (PDTC) strikingly dampened miR-21 silence-induced lipid deposition. Additionally, overexpression of miR-21 significantly abrogated the inflammatory cytokines secretion of IL-6 and increased IL-10 levels, the corresponding changes were also observed when silencing miR-21 expression, which was impeded by preconditioning with TLR4 antibody or PDTC. CONCLUSIONS: Taken together, these results corroborated that miR-21 could negatively regulate LPS-induced lipid accumulation and inflammatory responses in macrophages by the TLR4-NF-κB pathway. Accordingly, our research will provide a prominent insight into how miR-21 reversely abrogates bacterial infection-induced pathological processes of atherosclerosis, indicating a promising therapeutic prospect for the prevention and treatment of atherosclerosis by miR-21 overexpression.