Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer's disease.

Previous studies have shown that berberine has neuroprotective effects against Alzheimer's disease, including antagonizing tau phosphorylation, and inhibiting acetylcholinesterase activity and neural cell apoptosis. However, its low bioavailability and adverse reactions with conventional administration limit its clinical application. In this study, we prepared berberine nanoliposomes using liposomes characterized by low toxicity, high entrapment efficiency, and biodegradability, and modified them with lactoferrin. Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency. We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer's disease established by injection of amyloid-beta 1-42 into the lateral ventricle. Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus, reduced tau over-phosphorylation in the cerebral cortex, and improved mouse behavior. These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer's disease.

Prognostic significance of prognostic nutritional index and systemic immune-inflammation index in patients after curative breast cancer resection: a retrospective cohort study.

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

[Effects of qingyang toujie mixture in combination with prednisone tablet on Th1/Th2 cytokines in patients suffering from systemic lupus erythematosus].

OBJECTIVE: To research the effects of Qingyang Toujie Mixture (QTM) in combination with prednisone tablet on the balance of Th1 and Th2 (Th1/Th2) of systemic lupus erythematosus (SLE) patients of yin deficiency syndrome (YDS). METHODS: Totally 42 patients with SLE were recruited from clinics of internal medicine and hospitalization department of First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine from August 2009 to March 2011. They were randomly assigned to the treatment group (22 cases) and the control group (20 cases) according to the random digit table. Another 12 healthy subjects were recruited as the healthy control group from employees of First Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine and healthy students in physical examinations. All patients took prednisone tablet. The dosage was adjusted according to the severity of SLE activity index and the condition: 40 -60 mg per day for severe active stage; 20-40 mg per day for moderate active stage; 15 -20 mg per day for light active stage; and less than 15 mg per day for those in the stable stage, respectively. When patients' condition had been stabilized for 1 to 2 weeks, the dosage was gradually reduced according to the method of hormone reduction. In case of the recurrence of symptoms or when complicated with lupus nephritis or lupus encephalitis uncontrollable, standard shock therapy with Cyclophosphamide Injection (0.5-1 g/m2 body surface area, intravenous dripping, once every 4 weeks) was performed. Patients in the treatment group took QTM additionally, one dose daily, taken in two portions, once in the morning and once in the evening. Those in the control group took placebos additionally, one dose daily, taken in two portions, once in the morning and once in the evening. The therapeutic course was 6 months for all. No measure was taken for those in the healthy control group. Venous blood was withdrawal before and after treatment. Th1 cytokines (IFN-gamma, IL-12) and Th2 cytokines (IL-10, IL-4) were detected by ELISA. RESULTS: Compared with the healthy control group, the serum Th1 cytokines such as IL-12 and IFN-gamma, Th2 cytokines such as IL-10 and IL-4 increased, the Th1/Th2 ratios such as IFN-gamma/IL-4 and IL-12/IL-10 decreased in the treatment group and the control group before treatment (P < 0.01). Compared with before treatment in the same group, the serum Th1 cytokines such as IL-12 and IFN-gamma decreased, the serum Th2 cytokines such as IL-10 and IL-4 decreased, the ratios of Th1/Th2 cytokines such as IFN-gamma/IL-4 and IL-12/IL-10 increased in the treatment group (all P < 0.05). Compared with the control group after treatment, IL-4 decreased, and the ratio of IFN-gamma/IL-4 increased in the treatment group (P < 0.05). Fewer patients suffered from adverse reactions in the treatment group than in the control group (P < 0.01). CONCLUSION: QTM in combination with prednisone tablet was effective to improve the balance of Th1/Th2 cytokines, and alleviate the toxic and adverse reactions of hormone or immune inhibitors.

[Influence of Qingxiang San on substance P, somatostatin in rats model with the spleen and stomach wet heat syndrome].

OBJECTIVE: To observe the influence of Qingxiang San (QS) on substance P (SP), somatostatin (SS) in rats model of spleen and stomach wet heat syndrome. METHODS: 24 rats were divided into 3 groups (each group 8 rats) randomly: the normal control group (NCG), wet heat group (WHG), QS group (QSG). We set up the spleen and stomach wet heat syndrome of rats model by the composite factors such as greasy and sweet food, wet and hot environment, pathogen and so on. Then the contents of SP, SS were detected by radioimmuno assay. RESULTS: The content of SP, SS in WHG were obviously lower than NCG (P<0.01); QSG compared with WHG, the content of SP, SS increased (P<0.01); The content of SP obviously increased when QSG compared with NCG (P<0.01); About the content of SS, there was no significant difference between QSG and NCG (P>0.05), illustrating that QS can increase the content of SP, SS which had decreased. CONCLUSION: QS can regulate the content of SP and SS and increase them which had decreased.

[Effect of recombinant adenoviruses with CD/TK fusion suicide gene on human hepatocellular carcinoma cells].

OBJECTIVE: To investigate gene-therapy for human hepatocellular carcinoma with adenovirus vectors by double suicide gene CD/TK. METHODS: Double suicide gene CD/TK was liberated from eukaryotic vectors pCEA-CD/TK and subcloned into shuttle vectors, and the transfer plasmid pAdtrack-CMV-CD/TK was formed after linearizing with Pac 1. It was recombinated with pAdeasy-1 in bacteria BJ5183. The identified adenovirus plasmid was digested by Pac1 and was transfected into 293 cells to pack the adenoviruses. After PCR determination, its titre was measured, and the infection rate and efficacy were tested in human hepatocellular carcinoma cells. RESULTS: pAdtrack-CMV-CD/TK and pAd-CD/TK were tested by endonuclease digestion. Ad-CD/TK was produced in 293 cells, and the human hepatocellular carcinoma cells (SMMC7721) infected by Ad-CD/TK were killed after 5-FC was used, and bystander effects were observed. CONCLUSION: Recombinant adenoviruses with CD/TK fusion suicide gene have a high infection rate and efficacy for human hepatocellular carcinoma cells.