Cecropin-Loaded Zeolitic Imidazolate Framework Nanoparticles with High Biocompatibility and Cervical Cancer Cell Toxicity.

Cecropins (CECs) are insect venom-derived amphiphilic peptides with numerous pharmacological effects, including anti-inflammatory, antibacterial, antiviral, and anti-tumor activities. Cecropins induce tumor cell death by disrupting phospholipid membrane integrity. However, non-specific cytotoxicity and in vivo rapid degradation limit clinical application. Nanotechnologies provide novel strategies for tumor eradication, including nanocarriers that can precisely target drugs to tumor tissue. We report the fabrication of CEC-encapsulated zeolitic imidazolate framework 8 (ZIF-8) nanoparticles (CEC@ZIF-8 NPs) via the preparation of CEC@ZIF-8 NPs in pure water by one-pot stirring. This method yielded morphologically uniform NPs with 20 wt% drug loading capacity and 9% loading efficiency. The NP formulation protected CECs from proteasome degradation, enhanced peptide bioavailability, promoted HeLa tumor cell uptake, and increased antitumor efficacy compared to free CECs. In conclusion, this ZIF-8 encapsulation strategy may enhance the clinical applicability of CECs and other antitumor peptides.

[Effects of L-carnitine on serum levels of brain natriuretic peptide and N-terminal pro-brain natriuretic peptide and cardiac function in children with severe hand-foot-mouth disease].

OBJECTIVE: To observe the effects of L-carnitine treatment on serum levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) and cardiac function in children with heart dysfunction and severe hand-foot-mouth disease (HFMD). METHODS: A total of 120 children with severe HFMD were enrolled and randomly and equally divided into routine treatment group and L-carnitine treatment group. Thirty healthy children served as the control group. HFMD patients were given anti-fever and antiviral treatment as the basic treatment, while the patients in the L-carnitine treatment group were given L-carnitine as an adjuvant treatment to the basic treatment. Treatment outcomes were observed in the two groups. For all the subjects, serum levels of BNP and NT-proBNP and cardiac function parameters including left ventricular ejection fraction (LVEF), fractional shortening (FS), and cardiac index (CI) were measured at different time points before and after treatment. RESULTS: Before treatment, HFMD patients had significantly higher serum levels of BNP and NT-proBNP and heart rate but significantly lower LVEF, FS, and CI compared with the control group (P<0.05). After treatment, the L-carnitine treatment group had a significantly higher response rate than the routine treatment group (P<0.05). After 3 days of treatment, the serum levels of BNP and NT-proBNP, LVEF, FS, and CI were significantly reduced in the L-carnitine group (P<0.05); the L-carnitine group had significantly lower serum levels of BNP and NT-proBNP, LVEF, FS, and CI than the routine treatment group (P<0.05); there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and control groups (P>0.05). After 5 days of treatment, there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and routine treatment groups (P>0.05). Heart rate recovery was significantly slower in the routine treatment group than in the L-carnitine treatment group (P<0.05). CONCLUSIONS: As an adjuvant therapy for severe HFMD, L-carnitine treatment has satisfactory short-term efficacy in reducing the serum levels of BNP and NT-proBNP and improving cardiac function, thus improving clinical outcomes.

Non-viral vectors combined delivery of siRNA and anti-cancer drugs to reverse tumor multidrug resistance.

Multidrug resistance (MDR) of tumors is one of the main reasons for the failure of chemotherapy. Multidrug resistance refers to the cross-resistance of tumor cells to multiple antitumor drugs with different structures and mechanisms of action. Current strategies to reverse multidrug resistance in tumors include MDR inhibitors and RNAi technology. siRNA is a small molecule RNA that is widely used in RNAi technology and has the characteristics of being prepared in large quantities and chemically modified. However, siRNA is susceptible to degradation in vivo. The effect of siRNA therapy alone is not ideal, so siRNA and anticancer drugs are administered in combination to reverse the MDR of tumors. Non-viral vectors are now commonly used to deliver siRNA and anticancer drugs to tumor sites. This article will review the progress of siRNA and chemotherapeutic drug delivery systems and their mechanisms for reversing multidrug resistance.

Effects of tirofiban on large vessel occlusion stroke are modified by etiology and renal function.

OBJECTIVE: Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0-2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). RESULTS: Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non-LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. CONCLUSION: This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Association of circulating manganese levels with Parkinson's disease: A meta-analysis.

Whether systemic manganese (Mn) dysfunctions in Parkinson's Disease (PD) is still under ongoing debate. The recent reported studies on the circulating Mn levels in PD showed inconsistent results. A meta-analysis study was conducted to evaluate the association of circulating Mn levels with PD, and to clarify whether Mn should be considered as a potential risk factor for PD. A systematic searching was performed based on PubMed, web of science, and China National Knowledge Infrastructure (CNKI). Finally, 22 studies were identified, involving 637 PD patients and 802 health controls (HC) individuals for serum Mn, 1258 PD patients and 1304 HC individuals for peripheral blood Mn, and 195 PD patients and 196 HC individuals for cerebrospinal fluid (CSF) Mn. Forest plots were adopted to represent the comparison of the groups by assessing standardized mean difference with random effects model. This meta-analysis revealed a significantly increased serum Mn levels in PD patients (SMD=0.78; 95% CI [0.32, 1.24]; P=0.001), and it was further confirmed when serum, plasma and whole blood studies were analyzed together (SMD=0.58; 95% CI [0.25, 0.91]; P=0.001). Instead, no significant differences of CSF Mn were observed between PD patients and HC individuals (SMD=-0.09; 95% CI [-0.47, 0.29]; P=0.644). These results supported the notion that elevated Mn level should be a potential risk factor for PD, although the high heterogeneity and methodological limitations recommended caution in the interpretations for the present findings.

Association of Serum Manganese Levels with Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

Manganese (Mn) is one of the most studied environmental heavy metals linked to Alzheimer's disease (AD). However, it remains unclear whether serum Mn levels are associated with AD and mild cognition impairment (MCI, a prodromal stage of AD). We conducted a metaanalysis to analyze the serum Mn levels in patients with AD and MCI. A systematic database search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) identified 17 studies, including 836 cases and 1254 health controls (HC). Random-effects meta-analysis showed that patients with AD had significantly reduced serum Mn levels compared with HC subjects (SMD = -0.39; 95% CI (-0.71, -0.08); p = 0.015). MCI individuals had a tendency toward reduced serum Mn levels compared with HC subjects (SMD = -0.31; 95% CI (-0.70, 0.08); p = 0.117). A significant decrease in serum Mn levels was found in patients with cognitive impairment (including both AD patients and MCI patients) (SMD = -0.37, 95% CI (-0.60; -0.13); p = 0.002). Finally, no significant differences were observed between AD and MCI patients in serum levels (SMD = 0.24; 95% CI (-0.23, 0.72); p = 0.310). Our findings show that the serum Mn levels are lower in AD patients, and Mn deficiency may be a risk factor for AD.