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Amino acids which are essential nutrients for all cell types' survival are also recognised to serve as opportunistic/alternative fuels in cancers auxotrophic for specific amino acids. Accordingly, restriction of amino acids has been utilised as a therapeutic strategy in these cancers. Contrastingly, amino acid deficiencies in cancer are found to greatly impair immune functions, increasing mortality and morbidity rates. Dietary and supplemental amino acids in such conditions have revealed their importance as 'immunonutrients' by modulating cellular homeostasis processes and halting malignant progression. L-arginine specifically has attracted interest as an immunonutrient by acting as a nodal regulator of immune responses linked to carcinogenesis processes through its versatile signalling molecule, nitric oxide (NO). The quantum of NO generated directly influences the cytotoxic and cytostatic processes of cell cycle arrest, apoptosis, and senescence. However, L-lysine, a CAT transporter competitor for arginine effectively limits arginine input at high L-lysine concentrations by limiting arginine-mediated effects. The phenomenon of arginine-lysine antagonism can, therefore, be hypothesised to influence the immunonutritional effects exerted by arginine. The review highlights aspects of lysine's interference with arginine-mediated NO generation and its consequences on immunonutritional and anti-cancer effects, and discusses possible alternatives to manage the condition. However, further research that considers monitoring lysine levels in arginine immunonutritional therapy is essential to conclude the hypothesis.
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Arginina , Neoplasias , Arginina/metabolismo , Lisina , Dieta de Imunonutrição , Aminoácidos , Dieta , Neoplasias/terapiaRESUMO
In the tropics, coffee has been one of the most extensively cultivated economic crops, especially Arabica coffee (Coffea arabica L.). The coffee pulp, which includes phytochemicals with a proven antifungal action, is one of the most insufficiently utilized and neglected byproducts of coffee refining. In the current experiment, we carried out in silico screening of the isolated Arabica coffee phytochemicals for antifungal activity against Aspergillus fumigatus: a foodborne fungus of great public health importance. As determined by the molecular docking interactions of the library compounds indicated, the best interactions were found to occur between the nucleoside-diphosphate kinase protein 6XP7 and the test molecules Naringin (-6.771 kcal/mol), followed by Epigallocatechin gallate (-5.687 kcal/mol). Therefore, Naringin was opted for further validation with molecular dynamic simulations. The ligand-protein complex RMSD indicated a fairly stable Naringin-NDK ligand-protein complex throughout the simulation period (2-16 Å). In ADME and gastrointestinal absorbability testing, Naringin was observed to be orally bioavailable, with very low intestinal absorption and a bioavailability score of 0.17. This was further supported by the boiled egg analysis data, which clearly indicated that the GI absorption of the Naringin molecule was obscure. We found that naringin could be harmful only when swallowed at a median lethal dose between 2000 and 5000 mg/kg. In accordance with these findings, the toxicity prediction reports suggested that Naringin, found especially in citrus fruits and tomatoes, is safe for human consumption after further investigation. Overall, Naringin may be an ideal candidate for developing anti-A. fumigatus treatments and food packaging materials. Thus, this study addresses the simultaneous problems of discarded coffee waste management and antifungal resistance to available medications.
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Aspergillus fumigatus , Coffea , Humanos , Antifúngicos , Ligantes , Simulação de Acoplamento Molecular , Coffea/químicaRESUMO
Cancer is one of the leading causes of death worldwide, accountable for a total of 10 million deaths in the year 2020, according to GLOBOCAN 2020. The advancements in the field of cancer research indicate the need for direction towards the development of new drug candidates that are instrumental in a tumour-specific action. The pool of natural compounds proves to be a promising avenue for the discovery of groundbreaking cancer therapeutics. Elaeocarpus ganitrus (Rudraksha) is known to possess antioxidant properties and after a thorough review of literature, it was speculated to possess significant biomedical potential. Green synthesis of nanoparticles is an environmentally friendly approach intended to eliminate toxic waste and reduce energy consumption. This approach was reported for the synthesis of silver nanoparticles from two different solvent extracts: aqueous and methanolic. These were characterized by biophysical and spectroscopic techniques, namely, UV-Visible Spectroscopy, FTIR, XRD, EDX, DLS, SEM, and GC-MS. The results showed that the nanoconjugates were spherical in geometry. Further, the assessment of antibacterial, antifungal, and antiproliferative activities was conducted which yielded results that were qualitatively positive at the nanoscale. The nanoconjugates were also evaluated for their anticancer properties using a standard MTT Assay. The interactions between the phytochemicals (ligands) and selected cancer receptors were also visualized in silico using the PyRx tool for molecular docking.
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Elaeocarpaceae , Nanopartículas Metálicas , Antibacterianos/química , Química Verde , Nanopartículas Metálicas/química , Simulação de Acoplamento Molecular , Nanoconjugados , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prata/química , Prata/farmacologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Researchers are interested in Schiff bases and their metal complexes because they offer a wide range of applications. The chemistry of Schiff bases of heterocompounds has got a lot of attention because of the metal's ability to coordinate with Schiff base ligands. In the current study, a new bidentate Schiff base ligand, N-((1H-pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine (MPM) has been synthesized by condensing 6-methoxypyridine-3-amine with pyrrole-2-carbaldehyde. Further, MPM is used to prepare Cu(II) and Co(II) metal complexes. Analytical and spectroscopic techniques are used for the structural elucidation of the synthesized compounds. Both MPM and its metal complexes were screened against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Klebsiella pneumoniae species for antimicrobial studies. Furthermore, these compounds were subjected to in silico studies against bacterial proteins to comprehend their best non-bonded interactions. The results confirmed that the Schiff base ligand show considerably higher binding affinity with good hydrogen bonding and hydrophobic interactions against various tested microbial species. These results were complemented with a report of the Conceptual DFT global reactivity descriptors of the studied compounds together with their biological scores and their ADMET computed parameters.
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Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Cobalto/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/síntese química , Técnicas de Química Sintética , Complexos de Coordenação/síntese química , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Químicos , Modelos Moleculares , Estrutura Molecular , Bases de Schiff/química , Análise EspectralRESUMO
Genistein is an isoflavonoid present in high quantities in soybeans. Possessing a wide range of bioactives, it is being studied extensively for its tumoricidal effects. Investigations into mechanisms of the anti-cancer activity have revealed many pathways including induction of cell proliferation, suppression of tyrosine kinases, regulation of Hedgehog-Gli1 signaling, modulation of epigenetic activities, seizing of cell cycle and Akt and MEK signaling pathways, among others via which the cancer cell proliferation can be controlled. Notwithstanding, the observed activities have been time- and dose-dependent. In addition, genistein has also shown varying results in women depending on the physiological parameters, such as the early or post-menopausal states.
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Antineoplásicos Fitogênicos/farmacologia , Genisteína/farmacologia , Indutores da Angiogênese , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Descoberta de Drogas , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genisteína/análogos & derivados , Genisteína/química , Genisteína/uso terapêutico , Humanos , Glycine max/química , Relação Estrutura-AtividadeRESUMO
The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.
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Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Camellia sinensis/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vitis/química , Withania/química , Alcaloides/química , Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Flavonoides/química , Flavonoides/isolamento & purificação , Células Hep G2 , Humanos , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Folhas de Planta/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sementes/química , Transdução de Sinais , Taninos/química , Taninos/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação , alfa-Amilases/genética , alfa-Amilases/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
The increasing interest in developing potent non-toxic drugs in medicine is widening the opportunities for studying the usage of nanostructures in the treatment of various diseases. The present work reports a method for a facile and an eco-friendly synthesis of silver nanoparticles (AgNPs) using Terminalia chebula fruit extract (TCE). The obtained AgNPs was characterized by using different spectroscopic and microscopic techniques. The analysis of the results revealed that the as-obtained AgNPs have spherical morphology with an average diameter of 22 nm. Furthermore, the preliminary bioactivity evaluations revealed that the bio-conjugation of AgNPs, using TCE, significantly enhanced the antibacterial and anti-breast cancer potentials of the latter. The antibacterial activity of the as-prepared AgNPs showed that B. subtilis was more sensitive towards the AgNPs, followed by P. aeruginosa; while, E. coli and S. mutans showed comparatively minimal sensitivity toward the AgNPs. The IC50 values of TCE, AgNPs and TCE + AgNPs treatment of MCF-7 were found to be 17.53, 14.25 and 6.484 µg/mL, respectively. Therefore, it can be ascertained that the bio-conjugation may provide a headway with regard to the therapeutic employment of T. chebula, upon mechanistically understanding the basis of observed antibacterial and anticancer activities.
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Anti-Infecciosos , Bacillus subtilis/crescimento & desenvolvimento , Neoplasias da Mama/tratamento farmacológico , Citotoxinas , Frutas/química , Nanopartículas Metálicas , Extratos Vegetais/química , Prata , Terminalia/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Feminino , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Prata/química , Prata/farmacologiaRESUMO
Herein we report the synthesis and structural elucidation of two novel imine-based ligands, 2-(1,10-phenanthrolin-5-yl)imino)methyl)-5-bromophenol (PIB) and N-(1,10-phenanthrolin-5-yl)-1-(thiophen-3-yl)methanimine (PTM) ligands. An in vitro cytotoxicity assay of the synthesized molecules was carried out against breast, cervical, colorectal, and prostate cancer cell lines as well as immortalized human keratinocytes. The observations indicated that both the molecules possesses dose-dependent selective cytotoxicity of cancer cells with no detrimental effect on the normal cell lines. Furthermore, the detailed computational analysis of newly synthetized ligands (PIB and PTM) has been conducted in order to identify their most important parts from the perspective of local reactivity. The IC50 values of PIB treatment on MCF-7, HeLa, HCT-116 and PC-3 were 15.10, 16.25, 17.88, 17.55 and 23.86 micromoles, respectively. Meanwhile, the IC50 values of PTM on MCF-7, HeLa, HCT-116, PC-3 and HaCat were observed to be 14.82, 15.03, 17.88, 17.28 and 21.22 micromoles, respectively. For computational analysis, we have employed the combination of Density Functional Theory (DFT) calculations and MD simulations. DFT calculations provided us with information about structure and reactivity descriptors based on the electron distribution. Surfaces of molecular electrostatic potential (MEP) and averaged local ionization energy (ALIE) indicated the sites within studied molecules that are most reactive. These results indicated the importance of nitrogen atoms and OH group. Additionally, the values of bond dissociation for hydrogen abstraction showed that both molecules, especially the PTM, are stable toward the influence of autoxidation mechanism. On the other side, MD simulations gave us an insight how ligands interact with water molecules. Namely, the radial distribution functions (RDF) indicated that the hydrogen atom of the OH group in the case of the PIB has the most pronounced interactions with water.
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Proliferação de Células/efeitos dos fármacos , Iminas/farmacologia , Neoplasias/tratamento farmacológico , Fenantrolinas/farmacologia , Linhagem Celular Tumoral , Humanos , Iminas/síntese química , Iminas/química , Ligantes , Simulação de Acoplamento Molecular , Neoplasias/patologia , Fenantrolinas/síntese química , Fenantrolinas/química , Água/químicaRESUMO
Introduction: Non-alcoholic fatty liver disease (NAFLD) incidence has been rapidly increasing, and it has emerged as one of the major diseases of the modern world. NAFLD constitutes a simple fatty liver to chronic non-alcoholic steatohepatitis (NASH), which often leads to liver fibrosis or cirrhosis, a serious health condition with limited treatment options. Many a time, NAFLD progresses to fatal hepatocellular carcinoma (HCC). Nuclear receptors (NRs), such as liver X receptor-α (LXR-α) and closely associated farnesoid X receptor (FXR), are ligand-inducible transcription factors that regulate various metabolism-associated gene expressions and repression and play a major role in controlling the pathophysiology of the human liver. Withaferin A is a multifaceted and potent natural dietary compound with huge beneficial properties and plays a vital role as an anti-inflammatory molecule. Methods: In vivo: Swill albino mice were fed with western diet and sugar water (WDSW) for 12, 16, and 20 weeks with suitable controls. Post necropsy, liver enzymes (AST, ALT, and ALP) and lipid profile were measured by commercially available kits using a semi-auto analyzer in serum samples. Liver histology was assessed using H&E and MTS stains to check the inflammation and fibrosis, respectively, using paraffin-embedded sections and mRNA expressions of these markers were measured using qRT-PCR method. TGF-ß1 levels in serum samples were quantified by ELISA. In vitro: Steatosis was induced in HepG2 and Huh7 cells using free fatty acids [Sodium Palmitate (SP) and Oleate (OA)]. After induction, the cells were treated with Withaferin A in dose-dependent manner (1, 2.5, and 5 µM, respectively). In vitro steatosis was confirmed by Oil-Red-O staining. Molecular Docking: Studies were conducted using Auto Dock Vina software to check the binding affinity of Withaferin-A to LXR-α and FXR. Results: We explored the dual receptor-activating nature of Withaferin A using docking studies, which potently improves high-fat diet-induced NAFLD in mice and suppresses diet-induced hepatic inflammation and liver fibrosis via LXR/FXR. Our in vitro studies also indicated that Withaferin A inhibits lipid droplet accumulation in sodium palmitate and oleate-treated HepG2 and Huh7 cells, which may occur through LXR-α and FXR-mediated signaling pathways. Withaferin A is a known inhibitor of NF-κB-mediated inflammation. Intriguingly, both LXR-α and FXR activation inhibits inflammation and fibrosis by negatively regulating NF-κB. Additionally, Withaferin A treatment significantly inhibited TGF-ß-induced gene expression, which contributes to reduced hepatic fibrosis. Discussion: Thus, the LXR/ FXR dual receptor activator Withaferin A improves both NAFLD-associated liver inflammation and fibrosis in mouse models and under in vitro conditions, which makes Withaferin A a possibly potent pharmacological and therapeutic agent for the treatment of diet-induced NAFLD.
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Roses are popular ornamental plants all over the world. Rosa damascena Mill., also known as the damask rose, is a well-known scented rose species cultivated to produce essential oil. The essential oils obtained are high in volatile organic compounds (VOCs), which are in demand across the pharmaceutical, food, perfume, and cosmetic industries. Citronellol, nonadecane, heneicosane, caryophyllene, geraniol, nerol, linalool, and phenyl ethyl acetate are the most important components of the rose essential oil. Abiotic factors, including as environmental stress and stress generated by agricultural practises, frequently exert a selective impact on particular floral characteristics, hence influencing the overall quality and quantity of rose products. Additionally, it has been observed that the existence of stress exerts a notable impact on the chemical composition and abundance of aromatic compounds present in roses. Therefore, understanding the factors that affect the biosynthesis of VOCs, especially those representing the aroma and scent of rose, as a response to abiotic stress is important. This review provides comprehensive information on plant taxonomy, an overview of the volatolomics involving aromatic profiles, and describes the influence of abiotic stresses on the biosynthesis of the VOCs in damask rose.
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Lablab purpureus from the Fabaceae family has been reported to have antiviral properties and used in traditional medical systems like ayurveda and Chinese medicine and has been employed to treat a variety of illnesses including cholera, food poisoning, diarrhea, and phlegmatic diseases. The bovine alphaherpesvirus-1 (BoHV-1) is notorious for causing significant harm to the veterinary and agriculture industries. The removal of the contagious BoHV-1 from host organs, particularly in those reservoir creatures, has required the use of antiviral drugs that target infected cells. This study developed LP-CuO NPs from methanolic crude extracts, and FTIR, SEM, and EDX analyses were used to confirm their formation. SEM analysis revealed that the LP-CuO NPs had a spherical shape with particle sizes between 22 and 30 nm. Energy-dispersive X-ray pattern analysis revealed the presence of only copper and oxide ions. By preventing viral cytopathic effects in the Madin-Darby bovine kidney cell line, the methanolic extract of Lablab purpureus and LP-CuO NPs demonstrated a remarkable dose-dependent anti-BoHV-1 action in vitro. Furthermore, molecular docking and molecular dynamics simulation studies of bio-actives from Lablab purpureus against the BoHV-1 viral envelope glycoprotein disclosed effective interactions between all phytochemicals and the protein, although kievitone was found to have the highest binding affinity, with the greatest number of interactions, which was also validated with molecular dynamics simulation studies. Understanding the chemical reactivity qualities of the four ligands was taken into consideration facilitated by the global and local descriptors, which aimed to predict the chemical reactivity descriptors of the studied molecules through the conceptual DFT methodology, which, along with ADMET finding, support the in vitro and in silico results.
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Aims: To explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR). Main methods: We used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR. Key findings: In EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin. Significance: Dietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR.
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In the last decade, there have been significant advancements in the treatment of non-small cell lung cancer, including remarkable gains in detection, diagnosis, and therapy. The emergence of molecular targeted therapies, immunotherapeutic inhibitors, and antiangiogenesis medicines has largely fueled improvements in combination therapy and systemic treatments, all of which have dramatically ameliorated patient outcomes. The Moringa oleifera bioactive compounds have been effective in the suppression of cancers, making them the therapeutic agents of choice for the current investigation to treat MAGE-A presented in NSCLC. The ligand entrants were screened for their pharmacological properties, and 2,2-diphenyl-1,3-benzodioxole was stipulated as the lead candidate. 2,2-Diphenyl-1,3-benzodioxole exhibited better pharmacological properties and superior binding with branched-chain amino acids, making it an ideal candidate to address MAGE-A. The study concluded that addressing MAGE-A to impede their activity and antigenicity can be exploited as immunotarget(s).
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The current revision to Thailand's Narcotics Act (B.E. 2563) permits Thai corporations to produce cannabis (ganja) for therapeutic purposes, as well as conduct beneficial research and development in science and agriculture. While ganja possession, distribution, and use are still illegal in Thailand, the law removes certain elements of Cannabis sativa (including hemp) from the narcotic lists as of December 2020 and Thailand's narcotics board plans to remove them totally from the lists before the last quarter of 2022. The Thai Food and Drug Administration (Thai FDA) board maintains the exclusive licensing authority to assess applications and provide authorization due to the complexity of the registration process. In this view, we analyzed the guidelines for obtaining cannabis production license, and it was apparent that the announced law was in-line with regulations set-out by many countries in terms of security and prevention of misuse. The other criteria however fall merely onto the government gains, rather than public interests. To avoid the claimed state monopoly, several types of licensing should be issued in the future, depending on the genuine purpose of the farmers. The complete regulation process and conditions for obtaining a ganja growing license in Thailand are highlighted and discussed in this review.
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Cancers are known to have multifactorial etiology. Certain bacteria and viruses are proven carcinogens. Lately, there has been in-depth research investigating carcinogenic capabilities of some bacteria. Reports indicate that chronic inflammation and harmful bacterial metabolites to be strong promoters of neoplasticity. Helicobacter pylori-induced gastric adenocarcinoma is the best illustration of the chronic inflammation paradigm of oncogenesis. Chronic inflammation, which produces excessive reactive oxygen species (ROS) is hypothesized to cause cancerous cell proliferation. Other possible bacteria-dependent mechanisms and virulence factors have also been suspected of playing a vital role in the bacteria-induced-cancer(s). Numerous attempts have been made to explore and establish the possible relationship between the two. With the growing concerns on anti-microbial resistance and over-dependence of mankind on antibiotics to treat bacterial infections, it must be deemed critical to understand and identify carcinogenic bacteria, to establish their role in causing cancer.
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Background and Aim: Pestivirus, a genus of the Flaviviridae family, comprises viruses that affect bovines, sheep, and pigs. Symptoms, including hemorrhagic syndromes, abortion, respiratory complications, and deadly mucosal diseases, are produced in infected animals, which cause huge economic losses to the farmers. Bovine viral diarrhea virus-1, bovine viral diarrhea virus-2, classical swine fever virus, border disease virus, Bungowannah, Hobi-like, and atypical porcine pestivirus belonging to the Pestivirus genus were selected for the study. This study aimed to estimate the codon usage bias and the rate of evolution using the glycoprotein E2 gene. Furthermore, codon usage bias analysis was performed using publicly available nucleotide sequences of the E2 gene of all seven Pestiviruses. These nucleotide sequences might elucidate the disease epidemiology and facilitate the development of designing better vaccines. Materials and Methods: Coding sequences of the E2 gene of Pestiviruses A (n = 89), B (n = 60), C (n = 75), D (n = 10), F (n = 07), H (n = 52), and K (n = 85) were included in this study. They were analyzed using different methods to estimate the codon usage bias and evolution. In addition, the maximum likelihood and Bayesian methodologies were employed to analyze a molecular dataset of seven Pestiviruses using a complete E2 gene region. Results: The combined analysis of codon usage bias and evolutionary rate analysis revealed that the Pestiviruses A, B, C, D, F, H, and K have a codon usage bias in which mutation and natural selection have played vital roles. Furthermore, while the effective number of codons values revealed a moderate bias, neutrality plots indicated the natural selection in A, B, F, and H Pestiviruses and mutational pressure in C, D, and K Pestiviruses. The correspondence analysis revealed that axis-1 significantly contributes to the synonymous codon usage pattern. In this study, the evolutionary rate of Pestiviruses B, H, and K was very high. The most recent common ancestors of all Pestivirus lineages are 1997, 1975, 1946, 1990, 2004, 1990, and 1990 for Pestiviruses A, B, C, D, F, H, and K, respectively. This study confirms that both mutational pressure and natural selection have played a significant role in codon usage bias and evolutionary studies. Conclusion: This study provides insight into the codon usage bias and evolutionary lineages of pestiviruses. It is arguably the first report of such kind. The information provided by the study can be further used to elucidate the respective host adaptation strategies of the viruses. In turn, this information helps study the epidemiology and control methods of pestiviruses.
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INTRODUCTION: Cancer disease is known due to its unregulated proliferation of cells that have evolved from the body's regular cells. The disease develops as a result of epigenetic and genetic modifications, tumor suppressor gene inactivation, and oncogene activation. The present work describes an environmentally benign approach for the synthesis of manganese oxide nanoparticles (MnO2 NPs) using Gmelina arborea fruit extract (GAE) in an aqueous medium. METHODS: The study evaluated the formation of MnO2 NPs and their anticancer efficacy against MCF-7 breast cancer cell line. RESULTS: The formation of MnO2 NPs was confirmed through powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared MnO2 NPs was evident from XRD pattern. The morphology of the material was studied using SEM analysis, which suggested a rod-like nature with an average diameter of 50 nm. Further, the TEM and HR-TEM images confirmed the rod shape of the as-prepared MnO2 NPs with an interplanar distance of 0.271 nm. In addition, the concentric rings from selected area electron diffraction (SAED) analysis show the crystalline nature of the as-prepared material, which further supports the obtained XRD pattern. The anticancer efficacy of MnO2 NPs was evaluated against MCF-7 breast cancer cell line, which showed up to 96% inhibition of the cells at 400 µg/mL concentration. CONCLUSION: Bio-conjugation of MnO2 NPs can provide enough scope for the therapeutic use of Gmelina arborea, assuming appropriate mechanistic evaluations are conducted.
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Neoplasias da Mama , Nanopartículas Metálicas , Nanotubos , Neoplasias da Mama/tratamento farmacológico , Feminino , Frutas , Humanos , Células MCF-7 , Compostos de Manganês , Nanopartículas Metálicas/química , Óxidos , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
The aim of this research is to evaluate the relationship between genotype, phenotype, and chemical profiles of essential oil obtained from available Zanthoxylum spp. Three specimens of makhwaen (MK) distributed in Northern Thailand were genetically and morphologically compared with other Zanthoxylum spices, known locally as huajiao (HJ) and makwoung (MKO), respectively. HJ was taxonomically confirmed as Z. armatum while MKO and MK were identified as Z. rhetsa and Z. myriacanthum. Genetic sequencing distributed these species into three groups accordingly to their confirmed species. Essential oil of the dried fruits from these samples was extracted and analyzed for their chemical and physical properties. Cluster analysis of their volatile compositions separated MKO and MK apart from HJ with L-limonene, terpinen-4-ol, ß-phellandrene, and ß-philandrene. By using odor attributes, the essential oil of MKO and MK were closely related possessing fruity, woody, and citrus aromas, while the HJ was distinctive. Overall, the phenotypic characteristic can be used to elucidate the species among makhwaen fruits of different sources. The volatile profiling was nonetheless dependent on the genotypes but makwoung and makhwaen showed similar profiles.
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Gastric cancer inflicts significant health issues globally despite its declining incidence. The disease is known to be diagnosed at its advanced stages also corresponding with a poor prognosis for patients. The integral therapeutic choices to cure advanced gastric cancer have progressed swiftly in modern days. The preface of molecularly targeted therapeutic techniques would potentiate the personalized approach depending on patient-specific and tumor-specific features, exasperating the advantages of chemotherapy. Here we have reviewed the modern therapeutics such as immune therapy, chemotherapy, m-RNA based therapeutics, alongside evaluating the influence of age, sex and comorbidities-like factors on the occurrence of gastric cancer. Gastric cancer therapy consolidated target agents comprising inhibitors of programmed death-1(PD-1), human epidermal growth factor receptor 2 (HER2), mRNA, and epidermal growth factor receptor (EPGF). A combination of trastuzumab to platinum-mediated chemotherapy evolved has a typical front-line therapy in advanced gastric cancer. An attempt has been made to epitomize the contemporary-modern research on targeted therapy for advanced gastric cancer.
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[This corrects the article DOI: 10.3389/fonc.2021.741326.].