Alpha-momorcharin (α-MMC) is type-1 ribosome inactivating proteins (RIPs) with molecular weight of 29 kDa and has lots of biological activity. Our recent study indicated that the α-MMC purified from seeds of Momordica charantia exhibited distinct antiviral and antifungal activity. Tobacco plants pre-treated with 0.5 mg/mL α-MMC 3 days before inoculation with various viruses showed less-severe symptom and less reactive oxygen species (ROS) accumulation compared to that inoculated with viruses only. Quantitative real-time PCR analysis revealed that the replication levels of viruses were lower in the plants treated with the α-MMC than control plants at 15 days post inoculation. Moreover, the coat protein expression of viruses was almost completely inhibited in plants which were treated with the α-MMC compared with control plants. Furthermore, the SA-responsive defense-related genes including non-expressor of pathogenesis-related genes 1 (NPR1), PR1, PR2 were up-regulated and activities of some antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) were increased after the α-MMC treatment. In addition, the α-MMC (500 μg/mL) revealed remarkable antifungal effect against phytopathogenic fungi, in the growth inhibition range 50.35-67.21 %, along with their MIC values ranging from 100 to 500 μg/mL. The α-MMC had also a strong detrimental effect on spore germination of all the tested plant pathogens along with concentration as well as time-dependent kinetic inhibition of Sclerotinia sclerotiorum. The α-MMC showed a remarkable antiviral and antifungal effect and hence could possibly be exploited in crop protection for controlling certain important plant diseases.
The blood-brain barrier (BBB) presents a major challenge to effective treatment of neurological disorders, including lysosomal storage diseases (LSDs), which frequently present with life-shortening and untreatable neurodegeneration. There is considerable interest in methods for intravenous delivery of lysosomal proteins across the BBB but for the most part, levels achievable in the brain of mouse models are modest and increased lifespan remains to be demonstrated. In this study, we have investigated delivery across the BBB using a mouse model of late-infantile neuronal ceroid lipofuscinosis (LINCL), a neurodegenerative LSD caused by loss of tripeptidyl peptidase I (TPP1). We have achieved supraphysiological levels of TPP1 throughout the brain of LINCL mice by intravenous (IV) coadministration of recombinant TPP1 with a 36-residue peptide that contains polylysine and a low-density lipoprotein receptor binding sequence from apolipoprotein E. Importantly, IV administration of TPP1 with the peptide significantly reduces brain lysosomal storage, increases lifespan and improves neurological function. This simple "mix and inject" method is immediately applicable towards evaluation of enzyme replacement therapy to the brain in preclinical models and further exploration of its clinical potential is warranted.
Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients, particularly in patients with stage IIIA disease.
Background:The aim of this study was to systematically evaluate the prognostic role of pretreatment lactate dehydrogenase (LDH) concentration for survival in patients with lung cancer through performing a meta-analysis.Methods:PubMed, EMBASE, Cochrane Library, Web of Science, and China National Knowledge Infrastructure were searched for potentially relevant literature. The study and patients’ characteristics were extracted. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled to estimate the prognostic role of LDH in patients with lung cancer.Results:Fourteen studies with 4084 patients were included. Higher pretreatment LDH concentration was significantly associated with an increased risk of overall mortality in patients with lung cancer (HR = 1.49, 95% CI, 1.38–1.59). Subgroup analysis of studies also resulted in a significantly increased risk of mortality in patients with small cell lung cancer (SCLC, HR = 1.54, 95% CI, 1.43–1.67) or nonsmall cell lung cancer (NSCLC, HR = 1.25, 95% CI, 1.06–1.46), with high pretreatment LDH concentration. No significant between-study heterogeneity was observed (I2 = 12.0%, P = .321). No significant publication bias was found (P = .352) in the meta-analysis.Conclusion:The results suggested that higher pretreatment LDH concentration was associated with worse overall survival in patients with lung cancer. The findings may assist future research on anticancer therapy by targeting LDH and help predict prognosis in lung cancer patients. However, high-quality studies are required to further research and support these associations. Moreover, confounding factors such as patient ethnicity and tumor type should be considered in future studies.
Alpha-momorcharin (alpha-MMC) is a ribosome-inactivating protein (RIP) with excellent cytotoxicity to tumor cells. However, its strong immunogenicity and short plasma half-life limit its clinical applications. To overcome this, we have to PEGylated alpha-MMC using a branched 20 kDa (mPEG) (2)-Lys-NHS. Homogeneous mono-, di- and tri-PEGylated alpha-MMCs were synthesized, purified and characterized. In vitro and in vivo analysis indicated that the serial PEG-conjugates preserved moderate anti-tumor activity with 36% acute toxicity and at most 66% immunogenicity decrease. These results suggested the potential application of alpha-MMC-PEG conjugates as an anti-tumor agent.
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