Cancer, a disease that currently affects approximately 14 million people, is characterized by abnormal cell growth with altered replication capacity, which leads to the development of tumor masses without apoptotic control. Resistance to the drugs used in chemotherapy and their side effects stimulate scientific research seeking new therapies to combat this disease. Molecules from flora and fauna with cytotoxic activity against tumor cells have been studied for their potential to become a source of pharmaceutical agents. In this regard, snake venoms have a variety of proteins and peptides that have proven biotechnological potential. In several studies, antibacterial action and antitumor activity have been observed. One of the most widely studied venom components are phospholipases A2. Snake venom phospholipases A2 (svPLA2s) comprise a large class of molecules that catalyze the hydrolysis of the sn-2 position of phospholipids releasing fatty acids and lysophospholipids and are related to a broad spectrum of biotechnological activities. In addition to their specific cytotoxicity against some tumor cell lines, inhibitory activity of angiogenesis, adhesion and cell migration has been described. The antitumor activity of svPLA2s was observed both in vitro and in vivo, but little is known about the mechanism of action of these proteins in promoting this activity. In this review, the main structural and functional characteristics of svPLA2s are discussed, along with the mechanisms proposed, thus far, to explain their antitumor activity, targeting their potential use as a therapeutic alternative against cancer.
BackgroundImmunoassays for Plasmodium detection are, presently, most frequently based on monoclonal antibodies (MAbs); Polyclonal antibodies (PAbs), which are cheaper to develop and manufacture, are much less frequently used. In the present study we describe a sandwich ELISA assay which is capable of detecting P. vivax Lactate Dehydrogenase (LDH) in clinical blood samples, without cross reacting with those infected with P. falciparum.MethodsTwo recombinant proteins were produced from different regions of the P. vivax LDH gene. Two sandwich ELISA assay were then designed: One which uses mouse anti-LDH 1-43aa PAbs as primary antibodies (“Test 1”) and another which uses anti-LDH 35-305aa PAbs (“Test 2”) as the primary antibodies. Rabbit anti-LDH 1-43aa PAbs were used as capture antibodies in both ELISA assays. Blood samples taken from P. vivax and P. falciparum infected patients (confirmed by light microscopy) were analysed using both tests.Results“Test 2” performed better at detecting microscopy-positive blood samples when compared to “Test 1”, identifying 131 of 154 positive samples (85%); 85 positives (55%) were identified using “test 1”. “Test 1” produced one false positive sample (from the 20 malaria-free control) blood samples; “test 2” produced none. Kappa coefficient analysis of the results produced a value of 0.267 when microscope-positive blood smears were compared with “test 1”, but 0.734 when microscope-positive blood smears were compared with the results from “test 2”. Positive predictive value (PPV) and negative predictive value (NPV) were observed to be 98% and 22% respectively, for “Test 1”, and 99% and 45%, for “test 2”. No cross reactivity was detected with P. falciparum positive blood samples (n = 15) with either test assay.ConclusionBoth tests detected P. vivax infected blood and showed no evidence of cross-reacting with P. falciparum. Further studies will need to be conducted to establish the full potential of this technique for malaria diagnostics. As well as representing a promising new cost-effective novel technique for P. vivax diagnosis and research, the method for developing this assay also highlights the potential for PAb-based strategies for diagnostics in general.
It is believed that significant experimental and computational advances will arise in similar proportions in the coming years that will allow researchers to map the molecular regions responsible for their pharmacological actions, their respective mechanisms of action and their cell targets.
Phospholipases A inhibitors (PLIs) produced by venomous and non-venomous snakes play essential role in this resistance. These endogenous inhibitors may be classified by their fold in PLIα, PLIβ and PLIγ. Phospholipases A (PLAs) develop myonecrosis in snake envenomation, a consequence that is not efficiently neutralized by antivenom treatment. This work aimed to identify and characterize two PLIs from Amazonian snake species, Bothrops atrox and Micrurus lemniscatus. Liver tissues RNA of specimens from each species were isolated and amplified by RT-PCR using PCR primers based on known PLIγ gene sequences, followed by cloning and sequencing of amplified fragments. Sequence similarity studies showed elevated identity with inhibitor PLIγ gene sequences from other snake species. Molecular models of translated inhibitors' gene sequences resemble canonical three finger fold from PLIγ and support the hypothesis that the decapeptide (residues 107-116) may be responsible for PLA inhibition. Structural studies and action mechanism of these PLIs may provide necessary information to evaluate their potential as antivenom or as complement of the current ophidian accident treatment.
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