APN/CD13 inhibitor Ubenimex: A molecular chaperone of antineoplastic chemotherapeutic drugs / 中国药理学通报

Cytotoxic anti-neoplastic drugs are a kind of chemotherapeutic drugs that directly kill or inhibit the growth and proliferation of tumor cells, and it is one of the main drugs for the treatment of malignant tumors. These drugs may have toxic side effects on normal cells of human body (especially those with strong division and proliferation) when they are used to kill tumor cells. And patients may usually have adverse reactions even at a normal dose when using this kind of drugs. Due to the strong toxic side effects of cytotoxic chemotherapeutic drugs, their clinical application is limited. In recent years it has been found that aminopeptidase N inhibitor Ubenimex has a significant synergistic effect with anti-neoplastic chemotherapeutic drugs, which has the advantages of enhancing the therapeutic effect of drugs and reducing the toxic side effects of chemotherapeutic drugs. This review enumerates that the combination of Ubenimex and a variety of cytotoxic drugs can enhance the anti-tumor effect of cytotoxic drugs and reduce the occurrence of adverse reactions. In addition, the mechanism of combined use of Ubenimex in reversing drug resistance is also introduced. At the same time, is is further confirmed the clinical value of Ubenimex as an effective adjuvant in the treatment of malignant tumors, so as to provide a basis for clinical application.

A review on the prevention and treatment of congenital cytomegalovirus infection in mothers and infants / 中国当代儿科杂志

Human cytomegalovirus (HCMV) has a high infection rate worldwide, and 85%-90% of congenital cytomegalovirus (CMV) infections are asymptomatic at birth, with the clinical manifestations of hearing loss, psychomotor retardation, and learning disabilities, while 10%-15% are symptomatic infections. Some preterm infants develop CMV infection after birth, which can cause sepsis-like syndrome, thrombocytopenia, neutropenia, liver injury, and lung injury. However at present, women of childbearing age have a lack of awareness of CMV. CMV education and hygiene precautions for pregnant women can prevent CMV infections in themselves and congenital CMV infections in their infants. No definite results have been obtained from the studies on the effect of CMV vaccine and high-titer immunoglobulin in preventing congenital CMV infection in fetuses. Recent studies have confirmed that the specificity and sensitivity of urinary or salivary CMV-DNA detection have reached more than 98%, which contributes to the early diagnosis of congenital CMV infection. In addition to short-term treatment with ganciclovir, long-term treatment with oral valganciclovir is safe for symptomatic congenital CMV infection and appears to have a better clinical effect than the short-term treatment. In the future, it is necessary to strengthen the health education for pregnant women, enhance the mother-to-child management of CMV infection, conduct the research on CMV vaccine, and further standardize treatment regimens.

Effect of Qiling Decoction combined HAART on expression levels of Treg cells and Th17 in HIV/AIDS patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Qiling Decoction (QD) combined highly active antiretroviral treatment (HAART) on expression levels of peripheral blood Th17 and Treg cells in HIV/AIDS patients.</p><p><b>METHODS</b>Totally 55 HIV/AIDS patients were randomly assigned to the treatment group (28 cases) and the combination group (27 cases). Besides, 21 HIV negative patients were recruited as the healthy control group. Those in the treatment group received HARRT alone, while those in the combination group received HAART combined QD. The observation lasted for 24 weeks. Meanwhile, according to peripheral blood CD4+ T cell counts before treatment, HIV/AIDS patients were assigned to three subgroups. For patients in subgroup 1, 1 cells/microL < CD4+ T cell counts < or = 100 cells/microL; For patients in subgroup 2, 101 cells/microL < CD4+ T cell counts < or = 200 cells/lL; For patients in subgroup 3, 201 cells/microL < CD4+ T cell counts < or = 350 cells/microL. Expression of peripheral blood Th17 and Treg cells, and number of CD4+ T cell counts were detected using flow cytometry (FCM)in HIV/AIDS patients at the pre-treatment baseline, week 4, 12, and 24, as well as those in the healthy control group.</p><p><b>RESULTS</b>Compared with the healthy control group, CD4+ T cell counts and the baseline expression level of Th17 cells in the peripheral blood of HIV/AIDS patients significantly decreased, the expression level of Treg cells significantly increased P < 0.01). Compared with before treatment in the same group, CD4+ T cell counts all increased at week 4, 12, and 24 in the two treatment groups, showing statistical difference (P < 0.05, P < 0.01). There was no statistical difference in the effective rate at various CD4+ T cell levels between the two groups (P > 0.05). There was no statistical difference in expression levels of Th17 and Treg cells between the combination group and the treatment group at any time point (all P >0.05). The Th17/Treg ration significantly increased in the combination group after 24 weeks of treatment, showing statistical difference when compared with the treatment group (U = 2.135, P = 0.038).</p><p><b>CONCLUSION</b>QD could improve the immune balance of Th17/Treg cells, which might be one of its mechanisms for improving HIV/AIDS patients' immunity.</p>

Advances in the study of structural modifications of multi-target anticancer drug sorafenib / 药学学报

Sorafenib, the first oral multikinase inhibitor, can inhibit several kinases involved in tumor proliferation and angiogenesis including Raf, VEGFR, PDGFR, kit and so on. Due to the advantages of multi-mechanisms, broad-spectrum anticancer potency, and well-tolerated results in combination trials, more and more researchers have focused on the optimization of sorafenib in order to develop novel multi-targeted anticancer drugs. The present paper reviews the development of modification of sorafenib in recent years from two aspects: bio-isosterism and scaffold hopping. The structure-activity relationship (SAR) of these compounds is also summarized.

Significance of serum golgi protein 73 (GP73), alpha-fetoprotein (AFP) and lectin-reactive alpha-fetoprotein (AFP-L3) expresssion in primary hepatic carcinoma / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the alone and joint diagnostic value of serum golgi protein 73 (GP73), alpha-fetoprotein (AFP) and the percentage of lectin-reactive aipha-fetoprotein (AFP-L3) of primary hepatic carcinoma (PHC), and provide a novel method for diagnosis for PHC and screening for high-risk population.</p><p><b>METHODS</b>ELISA was used to detect the serum level of GP73, AFP and AFP-L3% in 81 cases of PHC,176 cases chronic hepatitis and liver cirrhosis, 30 cases other tumber cancer and 40 cases of health people.</p><p><b>RESULTS</b>The sensitivity of GP73, AFP and AFP-L3% in PHC is 77.78%, 62.69% and 51.85%, and the specificity is 84.55%, 86.99% and 96.34%, respectively. Joint detection could increase the sensitivity up to 88.89%.</p><p><b>CONCLUSION</b>GP73 was a high sensitivity mark for dignosis of PHC, while AFP-L3% was a high specificity mark for dignosis of PHC. The joint detection could improve PHC diagnostic performance.</p>

Clinical value of CD64 expression in adults with measles complicating bacterial pneumonia / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical value of expression of peripheral blood neutrophil CD64 in adults with measles complicating pneumonia.</p><p><b>METHODS</b>106 patients were divided into two groups by clinical manifestation and bacteria study: measles complicating bacterial pneumonia group and measles complicating viral pneumonia, using flow cytometry determination of CD64, C-reactive protein (CRP) and white blood cell (WBC) count.</p><p><b>RESULTS</b>The expression of CD64 in the bacterial pneumonia group with eruptive stage was (32.15 +/- 11.07) MFI, which was significantly higher than that in the group of with recovery stage (10.6 +/- 3.23) MFI (P < 0.01) and viral pneumonia (9.55 +/- 3.48) MFI (P < 0.01). These markers were considered positive if CD64 > or = 8.5 MFI, CRP > or = 10 mg/L and WBC > or = 9.05 x 10(9)/L. Their sensitivity was 78.12%, 80.48% and 59.37%. Their specificity was 76.19% ,67.67% and 64.28%. Their accuracy rate was 77.35%, 74.52%, 61.32%; CD64 has a positive relationship with CRP.</p><p><b>CONCLUSION</b>Compared to CRP, expression of peripheral blood neutrophil CD64 can be a better marker in the early diagnosis of patients with measles complicating bacterial pneumonia and as one of the indicators of disease conditions.</p>

The enhancing effect of tomato lectin modified liposomes of insulin on oral absorption in mice / 药学学报

<p><b>AIM</b>To investigate the enhancing effect on insulin absorption through GI tract in mice by using tomato lectin (TL) modified liposomes as the carrier.</p><p><b>METHODS</b>TL-phosphatidylethanolamine (PE) conjugate (TL-PE) was synthesized by using carbodiimide cross-linking method, then the compound was incorporated into the conventional liposomes of insulin. The agglutination test was performed to examine TL biological activities after synthesis and incorporation. When TL modified liposomes were administrated orally to the normal mice or diabetic mice at insulin dose of 350 u x kg(-1), the hypoglycemic effect was determinated according to the blood glucose level.</p><p><b>RESULTS</b>The blood glucose levels of the normal mice were reduced by modified liposomes. The glucose levels were (85 +/- 5)% at 4 h, (54 +/- 11)% at 8 h, (57 +/- 6)% at 12 h postdose compared with the glucose levels prior to oral administration respectively. However, the conventional liposomes and saline have no hypoglycemic effect. The blood glucose levels of the diabetic mice were obviously reduced by TL modified liposomes, the glucose levels were (38 +/- 13)% at 4 h, (50 +/- 15)% at 8 h, (50 +/- 16)% at 12 h respectively.</p><p><b>CONCLUSION</b>TL modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.</p>

Enhancing effect of Ulex europaeus agglutinin I modified liposomes on oral insulin absorption in mice / 药学学报

<p><b>AIM</b>To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier.</p><p><b>METHODS</b>UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (EDC), then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification. When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u x kg(-1) orally, the hypoglycemic effect was investigated according to the blood glucose level determination.</p><p><b>RESULTS</b>The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84 +/- 15)% at 4 h, (78 +/- 11)% at 8 h and (90 +/- 12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73 +/- 7)% at 4 h, (74 +/- 9)% at 8 h, (86 +/- 9)% at 12 h after oral administration.</p><p><b>CONCLUSION</b>The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.</p>