Comparing bacterial membrane interactions and antimicrobial activity of porcine lactoferricin-derived peptides.

Antibiotic treatment for microbial infections is under scrutiny due to increasing resistance to conventional antibiotics, warranting discovery of new classes of antibiotic agents. Antimicrobial peptides are part of the innate defense system found in nearly all organisms and possess bactericidal mechanisms that make it more difficult for bacteria to develop resistance. Porcine lactoferricin (LFP-20) is an antimicrobial peptide located in the N terminus of lactoferrin (LF). To develop novel cell-selective antimicrobial peptides with improved antimicrobial specificity compared with LFP-20, analogs LF2A LF-2, LF-4, and LF-6 were substituted with Ala, Ser, or Trp residues at different positions in the molecule. Analogs displayed a 2- to 16-fold higher antimicrobial activity than LFP-20, but were hemolytic at 64 µg/mL. Additionally, LFP-20, LF2A, LF-2, and LF-4 exhibited lower cytotoxicity against human peripheral blood mononuclear cells than LF-6 at concentrations of 25 to 100 µg/mL. To better understand the antibacterial mechanisms of LFP-20 and its analogs we examined their effect on the cytoplasmic membrane of Escherichia coli. The LFP-20 was not effective in depolarizing cytoplasmic membranes, whereas the other 3 analogs gradually dissipated the membrane potential of E. coli. Membrane potential increased with minimal inhibitory concentrations changes, demonstrating a correlation between bactericidal activity and membrane depolarization. Analogs were more efficient than LFP-20 in displacing lipopolysaccharide-bound dansyl-polymyxin B, which also rapidly increased 1-N-phenyl-naphthylamine uptake and release of cytoplasmic ß-galactosidase by increasing the permeability of the outer and inner membranes of E. coli. The 3 analogs caused an increased potential for calcein leakage from negatively charged lipid vesicles at high concentrations. Collectively, these results suggest that the first targets of LF-2, LF-4, and LF-6 in E. coli are cytoplasmic membranes. The 3 analogs exhibited lethal effects based on their abilities to disrupt membranes and permit transit of large intracellular components, such as calcein.

YES-associated protein 1 promotes adenocarcinoma growth and metastasis through activation of the receptor tyrosine kinase Axl.

Yes-associated protein 1 (YAP1), a nuclear effector of the Hippo pathway, plays an important role in tumorigenesis and progression of multiple cancers. The present study aimed to investigate the clinical significance of YAP1 and receptor tyrosine kinase Axl expression in human lung adenocarcinomas (LAC). We further explored possible molecular mechanisms mediated by YAP1 in LAC and gastric adenocarcinoma (GAC) cells. Forty-nine cases of human LAC and normal lung tissue (NLT) were collected. The expression of YAP1 and Axl was assessed by immunohistochemical assay through tissue microarray procedure and the clinicopathologic characteristics of all patients were analyzed. Using a loss of function approach, we investigated the effects of small hairpin RNA (shRNA)-mediated knockdown of YAP1 on the expression of Axl, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9), and the proliferative activities and invasive potential in LAC A549 and GAC SGC-7901 cell lines. As a result, the expression of YAP1 and Axl was found in LAC tissues with higher strong reactivity rate compared to the NLT (87.8 percent vs.60.8 percent, P=0.000; 77.6 percent vs 0.0 percent, P=0.000), but they did not associate with the age, gender, tumor size, TNM staging or lymph node metastases of LAC patients (each P>0.05). Spearman rank correlation analysis showed a positive correlation between YAP1 and Axl expression. Furthermore, knockdown of YAP in vitro markedly down-regulated the expression of Axl, PCNA and MMP-9, and inhibited the proliferation and invasion of LAC and GAC cells. Taken together, YAP1 and Axl are highly expressed in LAC compared to the NLT, and knockdown of YAP1 may inhibit the proliferation and invasion of adenocarcinoma cells through downregulation of the Axl pathway, representing a potential therapeutic target for the treatment of cancer.

Vitamin intake and glaucoma risk: A systematic review and meta-analysis.

There is currently a lack of high-quality research on the best dietary recommendations for patients with early glaucoma or at high risk for glaucoma. This meta-analysis aims to clarify the relationship between vitamin intake and glaucoma risk. Electronic databases, including PubMed, EMbase, ScienceDirect, Cochrane Database, Clinicaltrials.gov, and Google Scholar, were searched for publications indexed as of September 18, 2021. Data were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The I2 index was used to assess heterogeneity. We performed five meta-analyses of existing studies to summarize the evidence on the association between vitamin intake and glaucoma risk. The initial search identified 689 studies, eight of which (262,189 patients) met the eligibility criteria for the meta-analysis. The data showed that high-dose intake of vitamins A (OR=0.63, 95%CI [0.53, 0.76]) and B (OR=0.71, 95%CI [0.64, 0.80]) but not vitamins C (OR=0.69, 95%CI [0.48, 1.01]), D (OR=0.90, 95%CI [0.45, 1.83]), or E (OR=0.91, 95%CI [0.71, 1.16]) was associated with a low prevalence of glaucoma. The results of this study demonstrated that high-dose intake of vitamins A and B, but not vitamins C, D, or E, was associated with a low prevalence of glaucoma.

Estimation of the net energy and protein requirements for maintenance of male arctic foxes (Alopex lagopus) during the growth period1,2.

The maintenance requirements of net energy and net protein were assumed to represent the most accurate and important values totally for the animal's utilization. The objective of this experiment was to determine the net energy and net protein requirements for maintenance of growing arctic foxes. The experiments was evaluated using regression models estimated from data collected by means of indirect calorimetry, nitrogen balance trials, and digestion and metabolism experiments. Thirty-six growing arctic foxes (3 487 ± 261.7 g) at the age of 85 days were randomly assigned to four groups with 9 animals in each group. Arctic foxes were fed a complete formula diet at four intake levels (100%, or 80%, 60%, and 40% of feed requirements) from 24 July 2017 to 23 September 2017. Arctic foxes in each treatment were kept individually in respiration chambers after 1-d adaptation at day 2 for a 3-d balance trial and then at day 5 followed by a 3-d fasting period. The metabolizable energy intake (MEI), heat production in the fed state (HP), and retained energy (RE) of arctic foxes significantly decreased (P < 0.01) as the feed intake level decreased. Fasting heat production (FHP) of arctic foxes was not influenced by feed intake level (P > 0.05). The metabolizable energy maintenance requirement (MEm) and net energy maintenance requirement (NEm) estimated from the linear relationship between RE and MEI were 230 and 217 kJ/kg of body weight BW0.75/d, respectively. The MEm and NEm estimated by logarithmic regression of HP on MEI were 225 and 209 kJ/kg BW0.75/d, respectively. The net N maintenance requirement (NNm) and net protein maintenance requirement (NPm) estimated from the linear relationship between retained nitrogen (RN) and daily nitrogen intake (NI) were 179.6 mg/kg BW0.75/d and 1.123 g/kg BW0.75/d, respectively. It is concluded that NEm and NPm values obtained fill the net energy and protein requirements shortage, and provide the basic data for establishing the standard of nutrition demand of breeding arctic foxes in China.

Novel Heating-Induced Reversion during Crystallization of Al-based Glassy Alloys.

Thermal stability and crystallization of three multicomponent glassy alloys, Al86Y7Ni5Co1Fe0.5Pd0.5, Al85Y8Ni5Co1Fe0.5Pd0.5 and Al84Y9Ni4Co1.5Fe0.5Pd1, were examined to assess the ability to form the mixture of amorphous (am) and fcc-aluminum (α-Al) phases. On heating, the glass transition into the supercooled liquid is shown by the 85Al and 84Al glasses. The crystallization sequences are [am] → [am + α-Al] → [α-Al + compounds] for the 86Al and 85Al alloys, and [am] → [am + α-Al + cubic AlxMy (M = Y, Ni, Co, Fe, Pd)] → [am + α-Al] → [α-Al + Al3Y + Al9(Co, Ni)2 + unknown phase] for the 84Al alloy. The glass transition appears even for the 85Al alloy where the primary phase is α-Al. The heating-induced reversion from [am + α-Al + multicomponent AlxMy] to [am + α-Al] for the 84Al alloy is abnormal, not previously observed in crystallization of glassy alloys, and seems to originate from instability of the metastable AlxMy compound, in which significant inhomogeneous strain is caused by the mixture of solute elements. This novel reversion phenomenon is encouraging for obtaining the [am + α-Al] mixture over a wide range of high temperature effective for the formation of Al-based high-strength nanostructured bulk alloys by warm working.