Efficacy of azithromycin combined with intravenous immunoglobulin in the treatment of refractory mycoplasma pneumoniae pneumonia in children: a meta-analysis.

BACKGROUND: The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis. METHODS: A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability. RESULTS: Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11-1.25, P < 0.01) and shorter time to defervescence (MD = -2.12, 95% CI: -2.69--1.55), time to disappearance of pulmonary rales (MD = -2.90, 95% CI: -3.57--2.23), time to disappearance of cough (MD = -3.59, 95% CI: -4.51--2.67), and hospital length of stay (MD = -5.72, 95% CI: -8.80--2.64) in the experimental group receiving azithromycin combined with IVIG treatment compared to the control group treated with azithromycin alone. Additionally, there was no significant publication bias in this meta-analysis. CONCLUSION: Treatment with azithromycin combined with IVIG is more effective than treatment with azithromycin alone for children with RMPP. CLINICAL TRIAL NUMBER: Not applicable.

Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells.

Evodiamine (EVO) exhibits strong anti-cancer effects. However, the effect of EVO on the human colorectal cancer cell line HCT-116 has not been explored in detail, and its underlying molecular mechanisms remain unknown. In the present study, cell viability was assessed by Cell Counting Kit-8 (CCK-8). Cell cycle and apoptosis were measured by flow cytometry, and morphological changes in the nucleus were examined by fluorescence microscopy and Hoechst staining. Cell motility was detected by Transwell assay. ELISA was used to assess the protein levels of autocrine motility factor (AMF) in the cell supernatant, and protein expression was determined by Western blotting. Our results showed that EVO inhibited the proliferation of HCT-116 cells, caused accumulation of cells in S and G2/M phases, and reduced the levels of the secreted form of AMF. The protein levels of tumor suppressor protein (p53), Bcl-2 Associated X protein (Bax), B cell CLL/lymphoma-2 (Bcl-2), phosphoglucose isomerase (PGI), phosphorylated signal transducers and activators of transcription 3 (p-STAT3) and matrix metalloproteinase 3 (MMP3) were altered in cells treated with EVO. Taken together, our results suggest that EVO modulates the activity of the p53 signaling pathway to induce apoptosis and downregulate MMP3 expression by inactivating the JAK2/STAT3 pathway through the downregulation of PGI to inhibit migration of HCT-116 human colorectal cancer cells.

Diagnostic value of ultrasound for community-acquired pneumonia in children and its correlation with serum PCT level and PCIS.

OBJECTIVE: This study aimed to evaluate the diagnostic value of ultrasound for community-acquired pneumonia (CAP) in children. METHODS: Clinical information of children diagnosed with CAP and a control group of healthy children was collected, and lung ultrasound detection was performed. The lung ultrasound score (LUS) was assessed, and venous blood samples were collected. Serum indexes, including white blood cell count, were analyzed using an automatic immunoassay analyzer, while serum procalcitonin (PCT) level was measured using an enzyme-linked immunosorbent assay. The pediatric critical illness score (PCIS) was also performed for all subjects. RESULTS: White blood cell count, absolute neutrophil count, and respiratory index were significantly higher in the CAP group than those in the control group, while the oxygenation index was markedly lower. Ultrasound detection results showed that the CAP group exhibited significantly higher detection rates of pleural effusion, interstitial lung changes, lung consolidation, B-lines, air bronchogram signs, and reduced or absent lung sliding signs compared with the control group. In addition, the LUS and PCT levels were markedly higher in the CAP group, while the PCIS was notably lower. Further analysis exhibited that the LUS in the CAP group was significantly positively correlated with PCT levels and negatively correlated with PCIS. The receiver operating characteristic curve indicated that the area under the curve of LUS for diagnosing children with lung infection was 0.841. CONCLUSION: LUS is closely related to serum PCT level and PCIS. Lung ultrasound detection demonstrates high sensitivity and specificity, indicating its valuable clinical diagnostic utility for CAP in children.

Discovery of a novel lead characterized by a stilbene-extended scaffold against sepsis as soluble epoxide hydrolase inhibitors.

Recently, some inhibitors of soluble epoxide hydrolase (sEH) showed limited potential in treating sepsis by increasing survival time, but they have unfortunately failed to improve survival rates. In this study, we initially identified a new hit 11D, belonging to a natural skeleton known as stilbene and having an IC50 of 644 nM on inhibiting murine sEH. Natural scaffold-based sEH inhibitors are paid less attention. A combination of structure-activity relationships (SARs)-guided structural optimization and computer-aided skeleton growth led to a highly effective lead compound 70P (IC50: 4.0 nM). The dose-response study indicated that 70P (at doses of 0.5-5 mg/kg, ip.) significantly increased survival rates and survival time by reducing the levels of the inflammatory factors TNF-α and IL-6 in the liver. Interestingly, 70P exhibited much higher accumulation in the liver than in plasma (AUC ratio: 175). In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors.

Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways.

BACKGROUND: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). MATERIALS AND METHODS: KG1α, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. RESULTS: In KG1α cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. CONCLUSIONS: These results suggested that DADS suppressed the proliferation of KG1α cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

Effect of trichostatin A on anti HepG2 liver carcinoma cells: inhibition of HDAC activity and activation of Wnt/ß-Catenin signaling.

PURPOSE: To investigate the effect of deacetylase inhibitory trichostatin A (TSA) on anti HepG2 liver carcinoma cells and explore the underlying mechanisms. MATERIALS AND METHODS: HepG2 cells exposed to different concentrations of TSA for 24, 48, or 72h were examined for cell growth inhibition using CCK8, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining, and cell morphology changes under an inverted microscope. Expression of ß-catenin, HDAC1, HDAC3, H3K9, CyclinD1 and Bax proteins was tested by Western blotting. Gene expression for ß-catenin, HDAC1and HDAC3 was tested by q-PCR. ß-Catenin and H3K9 proteins were also tested by immunofluorescence. Activity of Renilla luciferase (pTCF/LEF-luc) was assessed using the Luciferase Reporter Assay system reagent. The activity of total HDACs was detected with a HDACs colorimetric kit. RESULTS: Exposure to TSA caused significant dose-and time-dependent inhibition of HepG2 cell proliferation (p<0.05) and resulted in increased cell percentages in G0/ G1 and G2/M phases and decrease in the S phase. The apoptotic index in the control group was 6.22±0.25%, which increased to 7.17±0.20% and 18.1±0.42% in the treatment group. Exposure to 250 and 500nmol/L TSA also caused cell morphology changes with numerous floating cells. Expression of ß-catenin, H3K9and Bax proteins was significantly increased, expression levels of CyclinD1, HDAC1, HDAC3 were decreased. Expression of ß-catenin at the genetic level was significantly increased, with no significant difference in HDAC1and HDAC3 genes. In the cytoplasm, expression of ß-catenin fluorescence protein was not obvious changed and in the nucleus, small amounts of green fluorescence were observed. H3K9 fluorescence protein were increased. Expression levels of the transcription factor TCF werealso increased in HepG2 cells following induction by TSA, whikle the activity of total HDACs was decreased. CONCLUSIONS: TSA inhibits HDAC activity, promotes histone acetylation, and activates Wnt/ß-catenin signaling to inhibit proliferation of HepG2 cell, arrest cell cycling and induce apoptosis.