BackgroundThe most common reason for malignant tumor treatment failure is recurrence and metastasis. Metastasis-associated in colon cancer-1 (MACC1) was originally identified as a metastatic and prognostic biomarker for colon cancer and later other solid tumors. Kangai 1 (KAI1), a marker of suppressor of metastasis, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or KAI1 in gastric adenocarcinoma (GAC) is unclear. In this study, we explored the relationship between MACC1 and KAI1 expression, as well as their respective correlation with clinicopathological features, to determine if either could be helpful for improvement of survival prognosis in GAC patients.MethodsThe expression levels of both MACC1 and KAI1 in 325 whole-tissue sections of GAC were examined by immunohistochemistry. Clinical data was also collected.ResultsMACC1 was significantly overexpressed in GAC tissues when compared to levels in normal gastric tissues; KAI1 was significantly down-expressed in GAC tissues when compared to levels in normal gastric tissues. Investigation of association between MACC1 and KAI1 protein levels with clinicopathological parameters of GAC indicated association between the expression of each with tumor grade, lymph node metastasis, invasive depth, and TNM stages. The overall survival time of patients with MACC1- or KAI1-positive GAC tumors was significantly shorter or longer than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or KAI1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with GAC.ConclusionsMACC1 and KAI1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for GAC.

The PK/PD profile of dosing regimens tested will assist in selecting the appropriate meropenem regimens for these patients. At a target of 40%T>MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤4 µg/mL. However, when a higher target (80% or 100%) is desired for difficult-to-treat infections, larger doses, prolonged infusions, shorter intervals, and/or combination therapy may be required.

The present study aimed to investigate the cardioprotective role of berberine in sepsis-induced cardiac dysfunction and consider the underlying mechanisms. C57BL/6J mice were randomized into four groups, namely, Control, lipopolysaccharide (LPS), LPS + berberine and LPS + N ω -nitro-L-arginine methyl ester (L-NAME) + berberine. A single dose (10 mg/kg body weight) of LPS was intraperitoneally administered to mice to induce cardiac dysfunction, whereas the Control group was administered with an equivalent volume of saline. In the LPS + berberine and LPS + L-NAME + berberine group, berberine (10 mg/kg body weight) dissolved in hot water was intraperitoneally administered 30 min after the LPS treatment. In the LPS + L-NAME + berberine group, L-NAME (100 mg/kg body weight) dissolved in saline was intraperitoneally administered 30 min before the LPS treatment. Then, ~6 h after the LPS treatment, a significant decrease was observed in the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Meanwhile, the plasma myocardial injury markers, inflammatory factors and oxidative stress levels were significantly increased in the LPS group compared with the Control group. The administration of berberine improved the ventricular function and decreased the plasma myocardial injury markers, inflammatory factors and oxidative stress levels. In addition, it increased the heart total nitric oxide synthase (NOS) activity and upregulated the protein expressions of p-Akt and phosphorylated endothelial (e)NOS, which indicated that the Akt/eNOS pathway was activated by berberine. However, the cardioprotective effects of berberine were counteracted by L-NAME, an NOS inhibitor, which inhibited the eNOS activity. In conclusion, berberine attenuated sepsis-induced cardiac dysfunction by upregulating the Akt/eNOS pathway in mice.

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