Data were generated automatically by the Octet User Software (version 3.1) and were subsequently analyzed from the resultant text files using Excel 2000. Drug resistance poses an increasing threat to global public health, and new antibiotic-resistant pathogens have continued to emerge [1], [2]. eCollection 2022. BmKn2 is an antimicrobial peptide (AMP) characterized from the venom of scorpion Mesobuthus martensii Karsch by our group. Galvez A., Gimenez-Gallego G., Reuben J.P., Roy-Contancin L., Feigenbaum P., Kaczorowski G.J., Garcia M.L. I would like to know how to get ride of this dangurous disease ? El-Ghlban S., Kasai T., Shigehiro T., Yin H.X., Sekhar S., Ida M., Sanchez A., Mizutani A., Kudoh T., Murakami H., Seno M. Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells. Martin-Eauclaire MF, Pimenta AM, Bougis PE, De Lima ME. Mucroporin, the first cationic host defense peptide from the venom of Lychas mucronatus. Koo G.C., Blake J.T., Talento A., Nguyen M., Lin S., Sirotina A., Shah K., Mulvany K., Hora D., Jr., Cunningham P., Wunderler D.L., McManus O.B., Slaughter R., Bugianesi R., Felix J., Garcia M., Williamson J., Kaczorowski G., Sigal N.H., Springer M.S., Feeney W. Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses invivo. Parabutoporin delayed neutrophil apoptosis via lipid raft-dependent activation of Akt (Remijsen etal., 2009). The histological morphology of the skin sections was observed. BmKbpp demonstrated strong antimicrobial activity against Gram-negative bacteria with a MIC range of 2.34.7M. Since you are going for chemo as well you may want to read some of the articles posted here https://www.cancertreatmentsresearch.com/category/increasing-chemo-efectivness/ and specifically this one https://www.cancertreatmentsresearch.com/if-chemotheraphy/, It was tough getting it trough customs, i needed a prescription, that no romanian doctor would give for a non pharmaceutical product, so the people from Labiofam were kind enough to send me a written prescription, although the customs didn t accept it at first, they finally understood that legaly it is forbidden to give a prescription for a medicine that is made with products from nature. Proc. The hemolytic activity of Kn2-7 was also significantly improved. Special emphasis is given to peptides that recognize Na(+)-, K(+)- and Ca(++)-channels of excitable cells. (Fig.4). The MIC of Kn2-7 treated with LTA against E. coli AB94012 was at least 25 g/mL. The MICs of Kn2-7 and BmKn2 treated with LTA against S. aureus were 25 and 12.5 g/mL, respectively. Figure 1. AMPs have both a cationic and amphiphilic nature. [Google Scholar] Zuo XP, Ji YH. Since the action of these toxins is blocked by tetrodotoxin, a . They could act on tumors directly by their intrinsic activity, by synergizing with existing chemotherapeutics, or by functioning as carrier vehicles for drugs with lower selectivity or bioavailability (Gaspar etal., 2013). The ePub format uses eBook readers, which have several "ease of reading" features High levels of stromal hyaluronan predict poor disease outcome in epithelial ovarian cancer. Das Gupta S., Gomes A., Debnath A., Saha A., Gomes A. Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian black scorpion venom: through mitochondrial pathway and inhibition of heat shock proteins. Vm24, a 36 amino acids peptide isolated from the venom of the scorpion V.mexicanus smithi (Gurrola etal., 2012) inhibits Kv1.3 channels of human lymphocytes with a Kd of 2.9pM and exhibits at least 1500-fold selectivity for Kv1.3 over other ion channels assayed. Mangmee S, Reamtong O, Kalambaheti T, Roytrakul S, Sonthayanon P. Molecules. (C) Histological morphologies of the skin in treated mice. http://scientificmania.blogspot.hu/2013/04/non-hodgkins-lymphoma-case-studies-with.html. SUMMARY Antibacterial and antifungal properties of alpha-helical, cationic peptides in the venom of scorpions from southern Africa. Would scorpions venom help this type of cancer? Despite favorable advancements, the classical methods available today, surgery, radiation and chemotherapy, still show a relatively low success rate and a high risk of reoccurrence. It possesses a single tyrosine residue available for radioiodination. PMC The investigation of the mechanism of action of chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. -. Ahigh molecular weight protein Bengalin from the Indian black scorpion (Heterometrus bengalensis CL Koch) venom having antiosteoporosis activity in female albino rats. This is not much so it may go into a capsule. Kn2-7 showed increased inhibitory activity against both Gram-positive bacteria and Gram-negative bacteria. Invitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines. Its all in her lymph nods. Bosmans F., Tytgat J. Voltage-gated sodium channel modulation by scorpion alpha-toxins. Petricevich V.L. Taken together, these data strongly suggest that Kn2-7 peptide can be developed as a topical therapeutic agent for treating bacterial infections. Toxins are the most thoroughly studied scorpion venom components. It increases blood vessels vasodilation and capillary permeability, and therefore causes arterial blood pressure to fall. Hong W, Li T, Song Y, et al. It has been reported that some NDBPs found in scorpion venoms such as parabutoporin and opistoporin, in addition to having antibacterial and antifungal activity, also presented immuno-modulating activity. It is a substrate for the angiotensin-converting enzyme (ACE), a proteolytic enzyme that inactivates bradykinin. From the cDNA library made from the venom gland of M.martensii Karsch, the sequence of BmK AGAP was identified, possessing high identity to the sodium channel modulator -toxins (Zeng etal., 2000). Remijsen Q., Verdonck F., Willems J. Parabutoporin, a cationic amphipathic peptide from scorpion venom: much more than an antibiotic. Recently, two venom peptides from the scorpion H. petersii were identified with effective inhibitory effect on herpes simplex virus type 1 (HSV-1) infection invitro. After the animals were euthanized, biopsy specimens of the excised wound area of the skin were collected and immediately fixed in phosphate-buffered formalin (10%, pH=7.4). AMPs are distributed among a wide range of species, including insects, plants, humans, and even single-celled organisms [6]. The ePub format is best viewed in the iBooks reader. In order to balance the proliferative advantage of ROS up-regulation versus its potential risks due to protein, lipid and DNA damage, cancer cells induce over-expression of ANXA2 to help lower the ROS when needed (Ref). These scorpion venom peptides commonly exhibit cytolysis or microbial inhibition functions. The combination of sympathetic excitation and the release of catecholamines in plasma generates a cascade of physiological events that can progress to arterial hypertension or hypotension, tachycardia or bradycardia, arrhythmia, unconsciousness, pulmonary edema, heart failure and death (Isbister and Bawaskar, 2014). Characterization of BmKbpp, a multifunctional peptide from the Chinese scorpion Mesobuthus martensii Karsch: gaining insight into a new mechanism for the functional diversification of scorpion venom peptides. Scorpion Venom - venommarket | snak venom, spider venom, bee venom . Through this site and linkages to other sites, I providegeneral information for educational purposes only. Have you given scorpion venom to your mother? Fjell C.D., Hiss J.A., Hancock R.E., Schneider G. Designing antimicrobial peptides: form follows function. Yan R., Zhao Z., He Y., Wu L., Cai D., Hong W., Wu Y., Cao Z., Zheng C., Li W. Anew natural alpha-helical peptide from the venom of the scorpion Heterometrus petersii kills HCV. Keywords: Antimicrobial peptides, scorpio maurus palmatus, Smp24, Smp43, cell death, pyroptosis, caspase-1, IL-1b. VmCT1, an antimicrobial peptide synthesized from the precursor DNA sequence found in a cDNA library from Vaejovis mexicanus smithi, was effective against Gram-positive and Gram-negative bacteria with a MIC of 525M, and showed only mild hemolysis (12% against human erythrocytes) at an even higher concentration of 50M (Ramirez-Carreto etal., 2012). GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. They found that margatoxin, a Kv1.3-selective peptide; isolated from the Centruroides margaritatus scorpion venom suppresses delayed-type hypersensitivity in guinea pigs, providing evidence that Kv1.3 blockade can inhibit immune response invivo (Koo etal., 1997). Preparation and invitro evaluation of I-131-BmK CT as a glioma-targeted agent. You can read about it on the web. These findings are important for the basic understanding of the mechanisms involved in macrophage activation following scorpion envenomation (Zoccal etal., 2011). One of the driving forces in the appearance of resistance is the exposure of the parasite population to artemisinin monotherapies for many years. metalloproteases that are able to cleave SNARE proteins in a mechanism similar to antare enzyme. In cases of severe scorpion envenomation, a systemic inflammatory response is triggered, with the release of inflammatory cytokines that contribute to immunological imbalance, multiple organ dysfunction and death (Magalhaes etal., 1999, Petricevich, 2010). The bioengineered OSK-1[E16K, K20D] is a synthetic toxin based on the template sequence of the OSK-1 peptide, isolated from the Orthochirus scrobiculosus scorpion venom. Toxins that act on sodium channels are the most relevant for their effects on mammals, including humans. Figure 4. It s like going to buy herbal tea with a prescription. Two factors are largely responsible for these decrements: increased deployment of insecticide-treated bednets and increased availability of highly effective artemisinin combination treatments. Weaver A.K., Liu X., Sontheimer H. Role for calcium-activated potassium channels (BK) in growth control of human malignant glioma cells. A group of mice was euthanized 4 hours after infection, and their skin viable counts were measured as a control. More than 1.2 million scorpion stings are registered globally every year. Scorpion Venom. They are disulfide-bridged peptides with a significantly constrained structure. She was diagnost with triple breast cancer in 2016 stage 2, after surgery , multiple chemo therapies, metastasis were found at her liver. The same group applied a similar approach to produce a potent variant of BmKn2, an antimicrobial peptide derived from the venom of the scorpion M. martensii Karsch (Zeng etal., 2004). Scorpion Venom: The Newest Treatment for a Deadly Cancer Zeng X.C., Corzo G., Hahin R. Scorpion venom peptides without disulfide bridges. Scorpion venom components that affect ion-channels function. Scorpionism represents a major health problem in several countries. . Contrary to classical antibiotics, the ligand-independent mechanism of bactericidal action of most AMPs implies that they are likely to be . BmKn2 and the seven derivatives of this peptide noted above were synthesized with amidated C-termini by More Biotech (Wuhan) Ltd., China. The voltage-gated K+ channel (Kv) was proposed as a target for immunosupression because 4-aminopyridine, a K+ channel blocker, inhibits T cell proliferation and interleukine-2 secretion (DeCoursey etal., 1984). Kn2-7 accumulated on the surface of E. coli, combined with the outer membrane, and then formed microspheres surrounded the bacteria. Eight mice per group were euthanized, and the viable counts of the surviving, (A) and (B) Secondary structure analysis of the Kn2-7 and BmKn2 peptides. Fu Y.J., An N., Li K., Zheng Y.L., Liang A.H. Chlorotoxin-conjugated nanoparticles as potential glioma-targeted drugs. Clipboard, Search History, and several other advanced features are temporarily unavailable. 3. Hello, my son who is 59 has been battling non-Hopkins lymphoma , he has has chemo, cold chemo, bone transplant, 3 different experiment treatment and each one has not worked and some has made matters worth. Scorpion Venom: Can It Really Cure What Ails You? BmHYA1 removed hyaluronan from the MDAMB-231 breast cancer cell line, which led to the down-regulation of a variant of CD44, a protein highly expressed in cancer cells (Feng etal., 2008). Kn2-7 or BmKn2 was prepared in gel form in 0.5% hydroxypropylcellulose to a final concentration of 5 mg/mL. TLR2, TLR4 and CD14 recognize venom-associated molecular patterns from Tityus serrulatus to induce macrophage-derived inflammatory mediators. Other treatments that may be specifically relevant are Gallium https://www.cancertreatmentsresearch.com/gallium-fighting-iron-avid-tumors/ and Bufalin https://www.cancertreatmentsresearch.com/huachansu-zhusheye-bufalin/ Disclaimer, National Library of Medicine Although P.berghei does not affect humans, it functions as a rodent model for malaria, since it goes through the same stages of development as P.falciparum after the infection with gametocytes by a mosquito bite. the display of certain parts of an article in other eReaders. Scorpion venom components that affect ion-channels function. Thanks a lot Daniel , we are always reading your articles , Dear Emad. aDepartamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologa, Universidad Nacional Autonma de Mxico, Avenida Universidad 2001, Cuernavaca 62210, Mexico, bDepartamento de Cincias Fisiolgicas, Instituto de Cincias Biolgicas, Universidade de Braslia, Braslia 70910-900, DF, Brazil, Scorpion venom components as potential candidates for drug development, GUID:E53C4A42-80CC-4F93-B479-C9F19289DBF1. Amorim-Carmo B, Parente AMS, Souza ES, Silva-Junior AA, Arajo RM, Fernandes-Pedrosa MF. Besides that, mucroporin-M1 also demonstrated antiviral activities against measles virus (EC50 of 3.52M), against the SARS coronavirus (EC50 of 7.12M), and against Influenza A virus subtype H5N1 (EC50 of 1.03M). 2022 May 26;9:887763. doi: 10.3389/fmolb.2022.887763. For many scorpion NDBPs the potential therapeutic concentration (the Minimum Inhibitory Concentration, MIC) against the tested microorganisms is very close to the concentration at which they are cytotoxic to mammalian cells (usually measured in erythrocyte hemolysis assays). Guo X.X., Ma C.B., Du Q., Wei R., Wang L., Zhou M., Chen T.B., Shaw C. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities. I am curently speaking with Susana Rodrguez ClTx effectively blocked the migration of STTGI and U251-MG human glioma cells, but ion channel depletion alone was not able to fully block glioma cell invasion (Lui etal., 2010). This is an idea I am proud of , Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasionhttp://www.ncbi.nlm.nih.gov/pubmed/25826056. As shown in Figure 5A and Figure 5B, when the peptide concentration increased, the killing rate also increased. The .gov means its official. Facebook YouTube Pinterest linkedin. In addition, the topical use of Kn2-7 effectively protected the skin of mice from infection in an S. aureus mouse skin infection model. It should be much cheaper than what you suggest above and if you can demonstrate you can not afford they will even give it for free. The Ryanodine Ca (++)-channel specific peptides . Structure, function, and chemical synthesis of Vaejovis mexicanus peptide 24: a novel potent blocker of Kv1.3 potassium channels of human T lymphocytes. Additionally, Kn2-7 was able to kill E. coli AB94012 rapidly, whereas the wild-type peptide BmKn2 was not able to kill E. coli AB94012 (Figure 5C). Fjell CD, Hancock RE, Cherkasov A. AMPer: a database and an automated discovery tool for antimicrobial peptides. Pharmacological Screening of Venoms from Five Brazilian, Mass-Spectrometry-Based Lipidome and Proteome Profiling of. Please enable it to take advantage of the complete set of features! Structure, function and mechanistic aspects of scorpion venom peptides Cracks were observed in the cell walls of the bacteria. The binding mode of Kn2-7 to the surface of E. coli was different from that of S. aureus. Conceived and designed the experiments: LC ZC CD. Action potentials are the physical depolarizing and repolarizing of cellular membranes of a brain cell along its axon. These data report on the identification of two novel CTX derivatives with multiple anti-glioma properties including anti-angiogenesis. Morgan G., Ward R., Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. the display of certain parts of an article in other eReaders. Therefore, the hemolytic activity of Kn2-7 was significantly decreased, compared to the wild-type peptide BmKn2. Scorpion venoms consist of a complex of several toxins that exhibit a wide range of biological properties and actions, as well as chemical compositions, toxicity, and pharmacokinetic and pharmacodynamic characteristics. A review. Please go through the info on this website as much as you can, and ask your son to do the same if possible. Scorpion Venom. Diverse bacterial mechanisms are responsible for the appearance of multi-resistance, including their rapid generation rates and chromosomal mutations, the acquisition of extra-chromosomal mobile DNA elements from other bacteria in the surroundings, together with some intrinsic mechanisms conferring the capacity to expel antibiotics from the cells (Alekshun and Levy, 2007). The latter toxin has a CS motif, typical of the -KTxs, however, was classified by its primary sequence into of the -KTx family. Bactericidal curves for Kn2-7 and BmKn2 were determined against S. aureus AB94004 and E. coli AB94012. Zeng X.C., Li W.X., Zhu S.Y., Peng F., Jiang D.H., Yang F.H., Wu K.L. And she stopped chemo and it returned even worse. Effective chemotherapeutic strategies are currently lacking which combat this deadly disease curatively. Though not related to each other in terms of structure or sequence, both synthetic peptides were able to inhibit the development of P. berghei ookinetes in the concentration range from 10 to 20M. The expansion of human civilization and the growth of human population have led to increased interaction with these arthropods, frequently resulting in accidents when people get stung (Chippaux and Goyffon, 2008). In this study, Kn2-7 was derived from BmKn2 to improve the antibacterial activity and decrease hemolytic activity. The results of BLI titrations and competition binding assays showed that Kn2-7 disrupted the cell walls of S. aureus and E. coli through binding to LTA and LPS, respectively. she will just vomit every thing ! Pharmacologic action of scorpion venom on intestinal smooth muscle. Scorpine was able to inhibit the development of P.berghei at the ookinete (with a median effective dose, ED50, of 0.7M) and gamete (with an ED50 of 10M) stages of the parasite's development. A couple of days ago dome doctor named Aaron Sarmiento who claims to be from the lab, mailed me regarding the dose and askwd to be kept informed on my father s condition. This is just myown personalopinion regardingwhat we have learned on this road. Contributed reagents/materials/analysis tools: LC ZC YW WL. It was also active against a few Gram-positive bacteria, but with higher MIC. Freire-Maia L, Pinto GI, Franco I. The tumour is 8cm and was diagnosed 2 weeks ago. In the first one, clones from a cDNA library from the scorpion Mesobuthus eupeus venom gland were identified, which encode for NDBPs meucin-24 and meucin-25. If it is accessible to you, I would certainly use it but do much more than that. Meanwhile, the MICs of the Kn2-7 and BmKn2 treated with LPS against S. aureus were 12.5 and 6.25 g/mL, respectively, and the MIC of the Kn2-7 mutant treated with LPS against E. coli was at least 25 g/mL. Beeton C., Wulff H., Standifer N.E., Azam P., Mullen K.M., Pennington M.W., Kolski-Andreaco A., Wei E., Grino A., Counts D.R., Wang P.H., LeeHealey C.J., Andrews B.S., Sankaranarayanan A., Homerick D., Roeck W.W., Tehranzadeh J., Stanhope K.L., Zimin P., Havel P.J., Griffey S., Knaus H.G., Nepom G.T., Gutman G.A., Calabresi P.A., Chandy K.G. Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Molecular mechanisms of antibacterial multidrug resistance. In low doses, -toxins provoke a strong depolarization of the cell membrane, followed by a drop in excitability. Kn2-7 exerted its antibacterial activity via a bactericidal mechanism. In addition, for liver tumors, you can consider doing chemo embolization at Frankfurt University Hospital in Germany, at Prof. Thomas Vogl http://radiologie-uni-frankfurt.de/content/e1269/e1621/index_ger.html. Characterization of BmKbpp, a multifunctional peptide from the Chinese scorpion Mesobuthus martensii Karsch: gaining insight into a new mechanism for the functional diversification of scorpion venom peptides. This peptide found in the venom blockssmall-conductance chloride channels that are highly relevant in some cancers for migration and invasion of the healthy cells. Another potent and highly selective inhibitor of Kv1.3 is the peptide ADWX-1 (IC50 of 1.89pM) which was designed using the structure of BmKTX as template. Rodriguez de la Vega R.C., Schwartz E.F., Possani L.D. 4). Scorpion venoms produced by the . Some scorpion proteins and peptides have shown both invitro and invivo effects on cancer cells, with one of them even reaching phase I and phase II clinical trials (Heinen and da Veiga, 2011). Keywords: To confirm the results of the BLI titrations, 250 g/mL of Kn2-7 or BmKn2 was mixed with an equal volume of 1 mg/mL LTA or LPS. Chemical synthesis and characterization of maurocalcine, a scorpion toxin that activates Ca. BMC Genomics. Later, a high molecular weight protein (72kDa) was identified, named bengalin, which has the anticancer activity against the human leukemic cell lines through induction of apoptosis, predominantly mediated by the mitochondrial pathway with the participation of pro and anti-apoptotic proteins, and with no significant death of normal human lymphocytes (Das Gupta etal., 2010). The T. serrulatus venom (TsV) is able to activate the complement system, as evidenced by the decreased serum lytic activity, activation of C3 and factor B and the induction of leukocyte chemotaxis (Bertazzi etal., 2005). It has been shown that Chlorotoxin has the ability to interact with chloride channels in membrane protein in e.g. Against PRSE, with a MIC of 10g/ml, it was 1000 times more effective than penicillin G. Ctriporin was effective when used as a topical antibiotic treatment in an S.aureus mouse skin wound infection model (Fan etal., 2011). Its solution structure, determined by NMR spectroscopy, consists of a small three-stranded antiparallel -sheet cross-linked to an -helix through three disulfide bonds and the fourth one links the small N-terminal beta strand to the rest of the molecule, characterizing the peptide as a knottin (Lippens etal., 1995). Although less potent than peptide K12, at a concentration of 50nM, both BmKbpp and BmKbpp-C induced significant shifts of the doseresponse curve of muscular contraction induced by bradykinin, with BmKbpp-C being more active than the whole peptide. Toxins or toxin-related scorpion venom components are best known for their deleterious effects on cells, tissues and organisms, but paradoxically, some of them have been shown to display activities that might be relevant for the development of pharmaceutical drugs. FOIA This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. However, Ctry2459 was not able to suppress an established infection due to its low bioavailability to infected cells. At first i spoke with them on whatsapp and than via email. Scorpion venom blocks bone loss. In addition, the topical use of Kn2-7 effectively protected the skin of mice from infection in an S. aureus mouse skin infection model. 2011;25:181200. ClTx does not bind to normal human tissues, including neuronal cells (DeBin etal., 1993, Lyons etal., 2002). You may notice problems with If so, feedback on it? Borges C.M., Silveira M.R., Aparecida M., Beker C.L., Freire-Maia L., Teixeira M.M. The Kn2-7 variant showed increased inhibitory activity against both Gram-negative and Gram-positive bacteria, being even more effective against clinical antibiotic-resistant strains of MRSA, MRCNS, PRSA and PRSE, than the original BmKn2. Kn2-7 showed increased inhibitory activity against both gram-positive bacteria and gram-negative bacteria.

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