Fat-to-muscle ratio as a predictor for dyslipidaemia in transitional-age youth.

BACKGROUND: Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth. METHODS: One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve. RESULTS: Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P < 0.05). The ideal values of FMR in diagnosing dyslipidaemia were 0.2224 for males and 0.4809 for females, while males had a higher AUC than females (0.7118 vs. 0.6656). Meanwhile, high FMR values were significantly associated with adverse outcomes of dyslipidaemia, hypercholesterolemia and hypertriglyceridaemia (P < 0.05). CONCLUSIONS: The FMR was positively correlated with the prevalence of dyslipidaemia. The FMR can be used as an effective body composition index for diagnosing dyslipidaemia, especially in males, and preventive strategies should be initiated in transitional-age youth to decrease obesity-related dyslipidaemia.

Involvement of Salicylic Acid in Anthracnose Infection in Tea Plants Revealed by Transcriptome Profiling.

Anthracnose is a major leaf disease in tea plant induced by Colletotrichum, which has led to substantial losses in yield and quality of tea. The molecular mechanism with regards to responses or resistance to anthracnose in tea remains unclear. A de novo transcriptome assembly dataset was generated from healthy and anthracnose-infected leaves on tea cultivars "Longjing-43" (LJ43) and "Zhenong-139" (ZN139), with 381.52 million pair-end reads, encompassing 47.78 billion bases. The unigenes were annotated versus Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), National Center for Biotechnology Information (NCBI) non-redundant protein sequences (Nr), evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) and Swiss-prot. The number of differential expression genes (DEGs) detected between healthy and infected leaves was 1621 in LJ43 and 3089 in ZN139. The GO and KEGG enrichment analysis revealed that the DEGs were highly enriched in catalytic activity, oxidation-reduction, cell-wall reinforcement, plant hormone signal transduction and plant-pathogen interaction. Further studies by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography (HPLC) showed that expression of genes involved in endogenous salicylic acid biosynthesis and also accumulation of foliar salicylic acid are involved in the response of tea plant to anthracnose infection. This study firstly provided novel insight in salicylic acid acting as a key compound in the responses of tea plant to anthracnose disease. The transcriptome dataset in this study will facilitate to profile gene expression and metabolic networks associated with tea plant immunity against anthracnose.

Inhibitory Effects of (-)-Epigallocatechin-3-gallate on Esophageal Cancer.

There is epidemiological evidence showing that drinking green tea can lower the risk of esophageal cancer (EC). The effect is mainly attributed to tea polyphenols and their most abundant component, (-)-epigallocatechin-3-gallate (EGCG). The possible mechanisms of tumorigenesis inhibition of EGCG include its suppressive effects on cancer cell proliferation, angiogenesis, DNA methylation, metastasis and oxidant stress. EGCG modulates multiple signal transduction and metabolic signaling pathways involving in EC. A synergistic effect was also observed when EGCG was used in combination with other treatment methods.

Bioavailability of Tea Catechins and Its Improvement.

Many in vitro studies have shown that tea catechins had vevarious health beneficial effects. However, inconsistent results between in vitro and in vivo studies or between laboratory tests and epidemical studies are observed. Low bioavailability of tea catechins was an important factor leading to these inconsistencies. Research advances in bioavailability studies involving absorption and metabolic biotransformation of tea catechins were reviewed in the present paper. Related techniques for improving their bioavailability such as nanostructure-based drug delivery system, molecular modification, and co-administration of catechins with other bioactives were also discussed.

Anthocyanin metabolism and its differential regulation in purple tea (Camellia sinensis).

Tea plants (Camellia sinensis) typically contain high-flavonoid phytochemicals like catechins. Recently, new tea cultivars with unique purple-colored leaves have gained attention. These purple tea cultivars are enriched with anthocyanin, which provides an interesting perspective for studying the metabolic flux of the flavonoid pathway. An increasing number of studies are focusing on the leaf color formation of purple tea and this review aims to summarize the latest progress made on the composition and accumulation of anthocyanins in tea plants. In addition, the regulation mechanism in its synthesis will be discussed and a hypothetical regulation model for leaf color transformation during growth will be proposed. Some novel insights are presented to facilitate future in-depth studies of purple tea to provide a theoretical basis for targeted breeding programs in leaf color.

The light-harvesting chlorophyll a/b-binding proteins of photosystem II family members are responsible for temperature sensitivity and leaf color phenotype in albino tea plant.

INTRODUCTION: Light-harvesting chlorophyll a/b-binding (LHCB) protein complexes of photosystem II are integral to the formation of thylakoid structure and the photosynthetic process. They play an important role in photoprotection, a crucial process in leaf development under low-temperature stress. Nonetheless, potential key genes directly related to low-temperature response and albino phenotype have not been precisely identified in tea plant. Moreover, there are no studies simultaneously investigating multiple albino tea cultivars with different temperature sensitivity. OBJECTIVES: The study aimed to clarify the basic characteristics of CsLHCB gene family members, and identify critical CsLHCB genes potentially influential in leaf color phenotypic variation and low-temperature stress response by contrasting green and albino tea cultivars. Concurrently, exploring the differential expression of the CsLHCB gene family across diverse temperature-sensitive albino tea cultivars. METHODS: We identified 20 putative CsLHCB genes according to phylogenetic analysis. Evolutionary relationships, gene duplication, chromosomal localization, and structures were analyzed by TBtools; the physiological and biochemical characteristics were analyzed by protein analysis websites; the differences in coding sequences and protein accumulation in green and albino tea cultivars, gene expression with maturity were tested by molecular biology technology; and protein interaction was analyzed in the STRING database. RESULTS: All genes were categorized into seven groups, mapping onto 7 chromosomes, including three tandem and one segmental duplications. They all own a conserved chlorophyll A/B binding protein domain. The expression of CsLHCB genes was tissue-specific, predominantly in leaves. CsLHCB5 may play a key role in the process of leaf maturation and senescence. In contrast to CsLHCB5, CsLHCB1.1, CsLHCB2, and CsLHCB3.2 were highly conserved in amino acid sequence between green and albino tea cultivars. In albino tea cultivars, unlike in green cultivars, the expression of CsLHCB1.1, CsLHCB1.2, and CsLHCB2 was down-regulated under low-temperature stress. The accumulation of CsLHCB1 and CsLHCB5 proteins was lower in albino tea cultivars. Greater accumulation of CsLHCB2 protein was detected in RX1 and RX2 compared to other albino cultivars. CONCLUSIONS: CsLHCB1.1, CsLHCB1.2, and CsLHCB2 played a role in the response to low-temperature stress. The amino acid sequence site mutation of CsLHCB5 would distinguish the green and albino tea cultivars. The less accumulation of CsLHCB1 and CsLHCB5 had a potential influence on albino leaves. Albino cultivars more sensitive to temperature exhibited lower CsLHCB gene expression. CsLHCB2 may serve as an indicator of temperature sensitivity differences in albino tea cultivars. This study could provide a reference for further studies of the functions of the CsLHCB family and contribute to research on the mechanism of the albino in tea plant.

Extraction of Squalene From Tea Leaves (Camellia sinensis) and Its Variations With Leaf Maturity and Tea Cultivar.

Squalene is a precursor of steroids with diverse bioactivities. Tea was previously found to contain squalene, but its variation between tea cultivars remains unknown. In this study, tea leaf squalene sample preparation was optimized and the squalene variation among 30 tea cultivars was investigated. It shows that squalene in the unsaponified tea leaf extracts was well separated on gas chromatography profile. Saponification led to a partial loss of squalene in tea leaf extract and so it is not an essential step for preparing squalene samples from tea leaves. The tea leaf squalene content increased with the maturity of tea leaf and the old leaves grown in the previous year had the highest level of squalene among the tested samples. The squalene levels in the old leaves of the 30 tested cultivars differentiated greatly, ranging from 0.289 to 3.682 mg/g, in which cultivar "Pingyun" had the highest level of squalene. The old tea leaves and pruned littering, which are not used in tea production, are an alternative source for natural squalene extraction.

Potent antitumor effects of a novel actinomycin D analog Leu5AMD.

Leu5AMD ([D-Val2, L-MeLeu5]2 AMD) is a novel actinomycin D (AMD) analog, in which both N-methylvalines were replaced by N-methylleucines. In the present study, an attempt has been made to investigate the effects of Leu5AMD on the proliferation of human gastric carcinoma cell line SGC-7901. The results showed that Leu5AMD inhibited the proliferation and induces apoptosis in SGC-7901 cells in a dose-dependent manner. Apoptosis induced by Leu5AMD was further confirmed by annexin V-FITC/PI dual staining assay. After treatment with Leu5AMD, the loss of mitochondrial potential and the decrease of bcl-2 gene expression were observed in apoptotic cells, suggesting that Leu5AMD may be involved in mitochondria and bcl-2 related apoptotic pathway. In addition, the in vivo antitumor effects of Leu5AMD on S-180 bearing mice and the acute toxicity on healthy mice were investigated. Treatment with Leu5AMD markedly suppressed the growth of Sarcoma xenograft. These results suggest that Leu5AMD may be used as a promising chemotherapeutical agent for patients affected by gastric carcinoma and other solid cancer.

Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI.

A novel antimicrobial peptide, polybia-MPI, was purified from the venom of the social wasp Polybia paulista. It has potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, but causing no hemolysis to rat erythrocytes. To date, there is no report about its antitumor effects on any tumor cell lines. In this study we synthesized polybia-MPI and studied its antitumor efficacy and cell selectivity. Our results revealed that polybia-MPI exerts cytotoxic and antiproliferative efficacy by pore formation. It can selectively inhibit the proliferation of prostate and bladder cancer cells, but has lower cytotoxicity to normal murine fibroblasts. In addition, to investigate the structure-activity relationship of polybia-MPI, three analogs in which Leu7, Ala8 or Asp9 replaced by L-Pro were designed and synthesized. L-Pro substitution of Leu7 or Asp9 significantly reduces the content of alpha-helix conformation, and L-Pro substitution of Ala8 can disrupt the alpha-helix conformation thoroughly. The L-Pro substitution induces a significant reduction of antitumor activity, indicating that the alpha-helix conformation of polybia-MPI is important for its antitumor activity. In summary, polybia-MPI may offer a novel therapeutic strategy in the treatment of prostate cancer and bladder cancer, considering its relatively lower cytotoxicity to normal cells.

Association of Tea Consumption with Risk of Alzheimer's Disease and Anti-Beta-Amyloid Effects of Tea.

Neurodegenerative disease Alzheimer's disease (AD) is attracting growing concern because of an increasing patient population among the elderly. Tea consumption is considered a natural complementary therapy for neurodegenerative diseases. In this paper, epidemiological studies on the association between tea consumption and the reduced risk of AD are reviewed and the anti-amyloid effects of related bioactivities in tea are summarized. Future challenges regarding the role of tea in preventing AD are also discussed.

Rat/mouse hemokinin-1, a mammalian tachykinin peptide, markedly potentiates the antinociceptive effects of morphine administered at the peripheral and supraspinal level.

Rat/mouse hemokinin 1 (r/m HK-1) is a mammalian tachykinin peptide whose biological functions are not fully understood. Our recent report showed that i.c.v. administration of r/m HK-1 could produce dose- and time-related antinociceptive effect at nanomole concentration, and naloxone significantly antagonized this effect. Thus, we provide indirect evidence favoring a role of NK1 supraspinal receptors in the inhibitory control of descending pain pathways, a role that seems to partially involve the activation of the endogenous opioid systems. Based on this report, the present study was conducted to further investigate the direct functional interaction between supraspinal tachykinin (r/m HK-1) and opioid systems. The results demonstrate that i.c.v. administration of r/m HK-1 (5 nmol/kg) could significantly potentiate the antinociceptive effects of morphine which was injected at peripheral and supraspinal level. These antinociceptive effects were blocked by prior treatment with the classical opioid receptors antagonist naloxone, indicating that the potentiated analgesic response is mediated by opioid-responsive neurons. Consistent with previous biochemical data, a likely mechanism underlying the peptide-mediated enhancement of opioid analgesia may center on the ability of r/m HK-1 to release endogenous opioid peptides. We suggest that there may be a cascade amplification mechanism in pain modulation when the two agents were co-administrated. The synergistic analgesic relationship of morphine and r/m HK-1 established here supports the hypothesis that supraspinal tachykinin and peripheral and central opioid systems have a direct functional interaction in the modulation of local nociceptive responses.

Effects and mechanisms of supraspinal administration of rat/mouse hemokinin-1, a mammalian tachykinin peptide, on nociception in mice.

Rat/mouse hemokinin 1 (r/m HK-1) is a novel tachykinin peptide whose biological functions are not fully understood. This work was designed to observe the effects of r/m HK-1 in pain modulation at supraspinal level in mice using tail-flick test. Intracerebroventricular (i.c.v.) administration of r/m HK-1 (0.1, 0.3, 1, 3 nmol/mouse) dose-dependently induced potent analgesic effect (ED(50) = 0.2877 nmol/mouse). When r/m HK-1 co-injected (i.c.v.) with SR140333 (a selective NK(1) receptor antagonist), SR140333 could fully antagonize the analgesic effect of r/m HK-1. The maximal analgesic effect of r/m HK-1 (3 nmol/mouse) could also be reversed by naloxone (i.p., 2 mg/kg). However, i.c.v. low dose administration of r/m HK-1 (10, 3, 1 pmol/mouse) induced hyperalgesia with a "U" shape curve, which means that the maximal hyperalgesic effect appeared at 3 pmol/mouse, and this effect of r/m HK-1 could also be fully blocked by SR140333. Interestingly, [Nphe(1)]NC(1-13)NH(2), a selective opioid receptor like-1 (ORL-1) receptor antagonist, could fully reverse the maximal hyperalgesic effect of r/m HK-1 (3 pmol/mouse). In addition, when r/m HK-1 co-injected (i.c.v.) with SR48968 (a selective NK(2) receptor antagonist), SR48968 could hardly affect the nociceptive effects of r/m HK-1 either at nanomole concentration or at picomole concentration. These findings suggested that r/m HK-1 might play an important role in pain modulation at supraspinal level in mice and these effects were first elicited through the activation of NK(1) receptor, subsequently, whether activation of the classical opioid receptor or the ORL1 receptor depending on the dose of i.c.v. administration of r/m HK-1.

Recurrent fetal loss associated with bilineal inheritance of type 1 autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 500 to 1,000 live births. Mutations in one of two genes, PKD1 and PKD2, account for the disease in most ADPKD families. Despite the relative high frequency of PKD1 mutant alleles, compound heterozygotes or diseased homozygotes have not been described. METHODS AND RESULTS: We report a family with type 1 ADPKD in which the marriage between affected first-degree cousins resulted in two live-born heterozygous offspring and two fetuses lost in late pregnancy. Genetic analysis with PKD1 and PKD2 flanking markers showed that this family is PKD1 linked (z(max) = 1.66 and -2.54 at thetas = 0.0 for intragenic markers for PKD1 [ie, KG8] and PKD2 [ie, SPP1], respectively). CONCLUSION: Given a 25% chance for mutant homozygosity in the offspring of this family, our findings suggest that homozygosity of PKD1 mutations in humans is embryonically lethal, as recently documented in Pkd1 knockout mice.

NPFF2 receptor is involved in the modulatory effects of neuropeptide FF for macrophage cell line.

Neuropeptide FF (NPFF) interacts with specific receptors to regulate diverse biological processes. Its modulatory effect in the immune field, however, has not been fully explored yet. Here, we report that NPFF2 receptors may be functionally expressed in two immune cell models, the primary peritoneal macrophage and RAW 264.7 macrophage. Firstly, the mRNA levels of NPFF2 receptor were up-regulated in macrophages when treated with LPS for 24 to 72 h. Subsequently, our data hinted that NPFF regulates the viability of both kinds of macrophages. After treatment with RF9, a reported antagonist for both NPFF receptors, delayed or inhibited the NPFF-induced macrophages viability augmentation, suggesting the involvement of NPFF2 receptor. Furthermore, down-regulation of nitric oxide (NO) synthases (NOSs) partially significantly inhibited the viability augmentation of macrophages induced by NPFF, implying a nitric oxide synthases- dependent pathway is involved. However, the NOSs are not the only route by which NPFF affects the viability of macrophages. Pharmacological inhibitors of NF-κB signal pathway also blocked the NPFF-induced macrophages growth, suggesting the involvement of the NF-κB signal pathway. The regulation activity of NPFF for macrophages suggests that NPFF could act as a potential hormone in the control of immune system. Collectively, our data provide new evidence about the immune modulatory effect of NPFF, which will be helpful in extending the scope of NPFF functions.

[Phthalic acid esters (PAEs) pollution in farmland soils: a review].

The environmental pollution and food safety problems caused by phthalic acid esters (PAEs) have been attracted 'extensive attention around the world. As a large PAEs producer and consumer, China is facing severe PAEs environmental pollution problems. This paper reviewed the present pollution status of six PAEs classified by the U.S. Environmental Protection Agency as the priority pollutants in China farmland soils, analyzed the sources of these six PAEs in this country, and discussed the absorption and accumulation characteristics of the PAEs in different crops as well as the bio-toxic effects of PAEs pollutants. The PAEs concentrations in China farmland soils are significantly higher those in the farmland soils of the United States and European countries. The main sources of PAEs in China farmland soils are atmospheric deposition, agricultural films, sewage sludge application, and wastewater irrigation. There exist significant differences in the characteristics of PAEs absorption, accumulation, and distribution among different crops. PAEs not only have negative effects on soil quality, crop growth, and crop physiological and biochemical properties, but also possess bio-accumulative characteristics. The weaknesses in current researches were pointed out, and the suggestions for the further researches were given, e. g., to expand the scope of PAEs pollution survey, to explore the toxic mechanisms of PAEs on crops, and to develop the techniques for in situ remediation of PAEs-polluted soils.

[Distribution characteristics of phthalic acid esters in soils and peanut kernels in main peanut producing areas of Shandong Province, China].

Surface soil (0-20 cm) and peanut kernel samples were collected in four main peanut producing areas of Shandong Province, and the contents of six PAEs chemicals that classified by the U. S. Environmental Protection Agency as priority pollutants were determined by gas chromatography (GC). The results indicated that the total concentration of six PAEs (sigma PAEs) ranged from 0.34 to 2.81 mg x kg(-1), and the mean was 1.22 mg x kg(-1). In four different areas, the order of sigmaPAEs concentration in soil was hilly area of middle southern Shandong > western plain of Shandong > Jiaodong Peninsula > northern plain of Shandong. The concentration of DBP in four main peanut producing areas of Shandong Province seriously exceeded the control limit in USA. The content of PAEs ranged from 0.17 to 0.66 mg x kg(-1) in peanut kernels, with the average value 0.34 mg x kg(-1) which was less than the suggested targets in USA and Europe and of low health risk. DEHP and DBP were the main components of PAEs both in soils and peanut kernels, with higher percentage content and detection rate. The sigma PAEs contents in soils or peanut kernels under plastic mulching were significantly higher than that of open field cultivation pattern. The PAEs concentrations in peanut kernels and soils had significant correlation, with the Pearson coefficient 0. 786 (sigma PAEs), 0.747 (DBP) and 0.511 (DEHP), respectively.

Membrane active antitumor activity of NK-18, a mammalian NK-lysin-derived cationic antimicrobial peptide.

As the increasing emergence of multi-drug resistant tumor cells, there is an urgent need for developing new chemotherapeutic agents. NK-lysin was a novel effector of cytotoxic T cells and natural killer (NK) cells and had broad antimicrobial activity. In this study, we developed a core region of NK-lysin termed NK-18, and studied its antitumor activity and possible action mode. Our results showed that NK-18 (with 18 amino acids) possesses potent antitumor activity against bladder and prostate cancer cells by disrupting the integrity of cell membrane, but has negligible hemolysis activity against mouse erythrocytes. In addition, CD spectra was employed to study its conformation in membrane mimicking environment. NK-18 takes a standard α-helical conformation in membrane mimicking environment, which could be accounted for its more potent antitumor activity compared with its low α-helical content homologous derivatives. These findings together with its shorter amino acid sequence and lower synthesis cost suggest that NK-18 could present an alternative therapeutic strategy to cancer chemotherapy and play a promising role in fighting the multi-drug resistant tumors.

Neuropeptide FF activates ERK and NF kappa B signal pathways in differentiated SH-SY5Y cells.

Neuropeptide FF (NPFF) has been reported to play important roles in regulating diverse biological processes. However, little attention has been focused on the downstream signal transduction pathway of NPFF. Here, we used the differentiated neuroblastoma cell line, dSH-SY5Y, which endogenously expresses hNPFF2 receptor, to investigate the signal transduction downstream of NPFF. In particular we investigated the regulation of the extracellular signal-regulated protein kinase (ERK) and the nuclear factor kappa B (NF-κB) pathways by NPFF in these cells. NPFF rapidly and transiently stimulated ERK. H89, a selective inhibitor of cyclic AMP-dependent protein kinase A (PKA), inhibited the NPFF-activated ERK pathway, indicating the involvement of PKA in the NPFF-induced ERK activation. Down-regulation of nitric oxide synthases also attenuated NPFF-induced ERK activation, suggesting that a nitric oxide synthase-dependent pathway is involved. Moreover, the core upstream components of the NF-κB pathway were also significantly activated in response to NPFF, suggesting that the NF-κB pathway is involved in the signal transduction pathway of NPFF. Collectively, these data demonstrate that nitric oxide synthases are involved in the signal transduction pathway of NPFF, and provide the first evidence for the interaction between NPFF and the NF-κB pathway. These advances in our interpretation of the NPFF pathway mechanism will aid the comprehensive understanding of its function and provide novel molecular insight for further study of the NPFF system.

In vitro and in vivo antitumor effects of novel actinomycin D analogs with amino acid substituted in the cyclic depsipeptides.

The actinomycin D (AMD) analogs in which the D-valine residues (the second amino acid residue in the cyclic depsipeptide of AMD) and the N-methyl-L-valine residues (the fifth amino acid residue in the cyclic depsipeptide of AMD) were replaced with D-Phe or l- and D-forms N-methylvalines, N-methylisoleucine, N-methylleucine, N-methylphenylalanine, N-methylalanine, and sarcosine were synthesized. The antimicrobial activity and cytotoxic activities of these compounds in vitro were investigated. The results showed that most D-valine substituted analogs had much lower antimicrobial activity and cytotoxic activities in vitro than AMD itself, but three N-methyl-L-valine substituted analogs had comparable or even more remarkable cytotoxic activities in vitro than AMD. Acute toxicities and antitumor effects of the N-methyl-L-valine substituted analogs in mice were also examined. The result showed that the acute toxicity of compound 4 L-methylleucine(5)-AMD analog is comparable to AMD itself and that of compound 3(L-Methylisoleucine(5)-AMD analog) is slightly more toxic, about 1.25-fold than AMD. However, the acute toxicity of compound 5 D-methylleucine5-AMD analog is about 2-fold lower than AMD. This suggested that the N-methyl-D-amino acid replacement in the cyclic ring might play a vital role in their decreased acute toxicities, and perhaps the N-methyl-D-leucine substituent is more favorable, though there may be a slight loss of antitumor activity. This finding may be helpful for the design and development of more potent antitumor agents together with low acute toxicity, and suggests that the N-methyl-D-leucine substituent has the potential to be used as antitumor drug lead.

A novel analog of antimicrobial peptide Polybia-MPI, with thioamide bond substitution, exhibits increased therapeutic efficacy against cancer and diminished toxicity in mice.

Polybia-MPI (MPI), a short cationic α-helical antimicrobial peptide, exhibited excellent anticancer activity and selectivity in vitro in our previous studies. To improve its in vivo application, we synthesized an analog (MPI-1) of MPI by replacing the C terminal amide -[CO-NH(2)] with thioamide -ψ[CS-NH(2)]. Although there is just one atom difference, the MPI-1 exhibited some surprising properties. In vitro studies revealed that MPI-1 exhibited relatively high lytic activity over MPI, whereas its stability to enzymatic degradation in serum was improved remarkably. Despite the enhanced toxicity in vitro, MPI-1 exhibited significantly lower mortality to mice than MPI at 75 mg/kg. Importantly, in vivo anticancer activity study indicated that MPI-1 could remarkably suppress the growth of sarcoma xenograft tumors more efficiently than MPI. Therefore, the significantly improved anticancer activity and predominantly lower in vivo toxicity might allow MPI-1 to be a good candidate for future anticancer treatment.