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Aim: The main goal was to create two new groups of indole derivatives, hydrazine-1-carbothioamide (4a and 4b) and oxadiazole (5, and 6a-e) that target EGFR (4a, 4b, 5) or VEGFR-2 (6a-e). Materials & methods: The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR/VEGFR-2, and the anti-proliferative properties were tested in vitro. Results: Compounds 4a (targeting EGFR) and 6c (targeting VEGFR-2) were the most effective cytotoxic agents, arresting cancer cells in the G2/M phase and inducing the extrinsic apoptosis pathway. Conclusion: The results of this study show that compounds 4a and 6c are promising cytotoxic compounds that inhibit the tyrosine kinase activity of EGFR and VEGFR-2, respectively.
[Box: see text].
Assuntos
Antineoplásicos , Proliferação de Células , Receptores ErbB , Indóis , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Indóis/química , Indóis/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , /farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor. The antiproliferative effects of the new compounds were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, cell cycle analysis, apoptosis detection by microscopy, quantitative reverse transcription-polymerase chain reaction, and immunoblotting, and EGFR enzyme inhibition assay. In silico analysis of the new oxadiazole derivatives indicated that these compounds target EGFR, and that compounds H4-A, H4-B, H4-C, and H4-E show similar molecular properties to erlotinib. Additionally, the results indicated that none of the synthesized compounds are carcinogenic, and that compounds H4-A, H4-C, and H4-F are nontoxic. Compound H4-A showed the best-fit score against EGFR pharmacophore model, however, the in vitro studies indicated that compound H4-C was the most cytotoxic. Compound H4-C caused cytotoxicity in HCT-116 colorectal cancer cells by inducing both apoptosis and necrosis. Furthermore, compounds H4-D, H4-C, and H4-B had potent inhibitory effect on EGFR tyrosine kinase that was comparable to erlotinib. The findings of this inquiry offer a basis for further investigation into the differences between the synthesized compounds and erlotinib. However, additional testing will be needed to assess all of these differences and to identify the most promising compound for further research.
Assuntos
Antineoplásicos , Receptores ErbB , Simulação de Acoplamento Molecular , Naproxeno , Oxidiazóis , Receptores ErbB/antagonistas & inibidores , Humanos , Oxidiazóis/farmacologia , Oxidiazóis/química , Oxidiazóis/síntese química , Naproxeno/farmacologia , Naproxeno/análogos & derivados , Naproxeno/química , Naproxeno/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Proliferação de Células/efeitos dos fármacosRESUMO
INTRODUCTION/BACKGROUND: Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase. MATERIALS AND METHODS: The new derivatives were synthesized by conventional organic methods, and their structure was versified by IR, 1HNMR, 13CNMR, and mass spectroscopy. In silico investigation was carried out to identify the compounds' target, molecular similarity, ADMET, and toxicity profile. The cytotoxic activity of the prepared compounds was evaluated in vitro against three human cancer cell lines (DLD1 colorectal adenocarcinoma, HeLa cervical cancer, and HepG2 hepatocellular carcinoma). The effects of the leading compound on cell cycle progression and apoptosis induction were investigated by flow cytometry, and the specific apoptotic pathway triggered by the treatment was evaluated by RT-PCR and immunoblotting. Finally, the inhibitory activities of the new compounds against VEGFR-2 was measured. RESULTS: The designed derivatives exhibited comparable binding positions and interactions to the VEGFR-2 binding site to that of sorafenib (a standard VEGFR-2 tyrosine kinase inhibitor), as determined by molecular docking analysis. Compound 4b was the most cytotoxic compound, achieving the lowest IC50 against HeLa cells. Compound 4b, a strong representative of the synthesized series, induced cell cycle arrest at the G2/M phase, increased the proportion of necrotic and apoptotic HeLa cells, and activated caspase 3. The EC50 value of compound 4b against VEGFR-2 kinase activity was comparable to sorafenib's. CONCLUSION: Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.
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INTRODUCTION: Allosteric inhibition of EGFR Tyrosine Kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies. METHOD: A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy. Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. RESULT: All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity. CONCLUSION: Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.
RESUMO
Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Three compounds (4b, 4c, and 4d) exhibited cytotoxicity against two of the three cell lines tested, five compounds (3, 4a, 5a, 5b, and 5e) were toxic to one cell line, while two compounds (5c and 5d) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR-2) kinase activity data, Compound 4d was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound 4d arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound 4d has shown promising results for future research as a potent VEGFR-2 tyrosine kinase inhibitor.
Assuntos
Antineoplásicos , Benzamidas , Benzoatos , Estrutura Molecular , Relação Estrutura-Atividade , Benzamidas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular , Proliferação de Células , Antineoplásicos/química , Inibidores de Proteínas Quinases/farmacologia , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Desenho de FármacosRESUMO
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT-116, HeLa, and HT-29â cell lines) as evaluated by the MTT assay. Compoundâ 3 b (EGFR-targeting) and compoundâ 6 e (VEGFR-2-targeting) possessed the highest antiproliferation activity, were cancer-selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR-2 enzyme inhibitory activity, respectively. The structure-activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti-tumor activity. In conclusion, the findings of the current study suggest that compoundsâ 3 b and 6 e are promising cytotoxic agents that act by inhibiting EGFR and VEGFR-2 tyrosine kinases, respectively.
Assuntos
Antineoplásicos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Proliferação de Células , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Fator A de Crescimento do Endotélio Vascular/farmacologia , Antineoplásicos/química , Relação Estrutura-Atividade , Receptores ErbB/metabolismo , Células HT29 , Ácidos Carboxílicos/farmacologia , Inibidores de Proteínas Quinases/química , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Desenho de FármacosRESUMO
Cephalostatin 1, a potent anti-cancer agent, is a natural bis-steroidal alkaloid that causes cell death in the subnanomolar to picomolar ranges via an atypical apoptosis pathway. Although cephalostatin 1 is a highly effective anticancer drug, its availability limits its utilization. We previously reported the synthesis of two 12'α-hydroxy derivatives of cephalostatin 1 that induce cell death by activating the ER stress apoptosis signaling pathway. For the current work, we synthesized six C11-functionalized cephalostatin 1 analogues (CAs) to evaluate their biological activity. For the cytotoxic compounds, the induced apoptotic pathway was investigated. The C11-functionalized cephalostatin 1 analogues 5 and 6 (CA5 and CA6) were found to exhibit cytotoxic activity against K-562 leukemia cells, MCF-7 breast cancer cells and DU-145 prostate cancer cells, while the remaining four analogues did not show anti-tumor activities against any of the cell lines. Our results indicated that CA5 and CA6 induced cell death via the atypical ER-dependent apoptosis pathway; they increased the expression of Smac/DIABLO, an inhibitor of inhibitors of apoptosis (IAPs), which in turn facilitated the activation of different caspases including the ER-caspase 4 without cytochrome c release from mitochondria. CA5 and CA6 are promising anticancer agents due to their low GI50, the remarkable apoptosis pathway they induce which can overcome chemoresistance, and their very low toxicity to normal cells making them cephalostatin 1 utilizable alternatives.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fenazinas/química , Fenazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Esteroides/química , Esteroides/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Células MCF-7 , Conformação Molecular , Fenazinas/síntese química , Compostos de Espiro/síntese química , Esteroides/síntese química , Células Tumorais CultivadasRESUMO
Background: Hypercoagulability and hypofibrinolysis are among the symptoms exhibited by diabetic patients. Our study aimed to address the polymorphic nature of Alu DNA fragment in the human tissue plasminogen activator gene within diabetes mellitus (DM) Jordanian patients. Methods: Genomic DNA was isolated from 76 DM patients and 60 non-diabetic Jordanian individuals, and the Alu fragment was amplified using PCR. Results: The results showed that 80% of the non-diabetic Jordanian subjects were homozygotes for the deletion of the Alu fragment (Alu-/-), 16.7% were homozygotes for its insertion (Alu+/+), and 3.3% were heterozygotes (Alu+/-). Besides, 36.8% of the diabetic patients exhibited the Alu-/- or Alu+/- genotype, and 26.3% were Alu+/+. The Alu-/- genotype occurred less frequently in the diabetic individuals. Conclusion: The high frequency of the Alu-/- genotype constitutes a protective deletion with respect to DM within the normal subjects.
Assuntos
Elementos Alu/genética , Diabetes Mellitus/genética , Polimorfismo Genético , Ativador de Plasminogênio Tecidual/genética , Alelos , Frequência do Gene , Humanos , JordâniaRESUMO
The current study was conducted to compare the cytotoxicity of two stereospecific cephalostatin 1 analogues (CAs) against several human normal cell types and cancer cell lines and to determine their cytotoxic mechanism. Both CA analogues induced apoptosis and were cytotoxic with 50% growth inhibition (GI50) at ~1µM or less in six human cancer cell lines but neither analogue at 10µM killed more than 14% of any of three types of normal human cells suggesting their cytotoxicity is cancer-specific. CA treatment inhibited clonogenic tumor growth and activated caspase 3 and 9 but not caspase 8. CA-induced apoptosis was inhibited by the pan caspase inhibitor indicating the importance of caspase activation. CA treatment released smac/DIABLO but not cytochrome c from mitochondria and induced phosphorylation of eIF-2 and the activation of procaspase 4 in cancer cells, similar to cell treatment with thapsigargin, a known endoplasmic reticulum (ER) stress inducer. Finally, cells pretreated with a caspase 4 inhibitor were resistant to CA-induced apoptosis. In conclusion, both CAs induced apoptosis by triggering ER stress. Because of their ease of synthesis and low GI50, these cephalostatin analogues represent promising anticancer drugs.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fenazinas/química , Fenazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Esteroides/química , Esteroides/farmacologia , Proteínas Reguladoras de Apoptose , Caspases Iniciadoras/metabolismo , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células K562 , Células MCF-7 , Proteínas Mitocondriais/metabolismoRESUMO
BACKGROUND: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. MATERIALS AND METHODS: T47D human breast cancer cells were treated with 2-deoxy- D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent- phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. RESULTS: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. CONCLUSIONS: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Butionina Sulfoximina/farmacologia , Desoxiglucose/farmacologia , Doxorrubicina/farmacologia , Adesões Focais/efeitos dos fármacos , Actinas/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antimetabólitos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/metabolismo , Adesão Celular , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Mitose/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: ADF/cofilin proteins are key modulators of actin dynamics in metastasis and invasion of cancer cells. Here we focused on the roles of ADF and cofilin-1 individually in the development of polarized migration of rat mammary adenocarcinoma (MTLn3) cells, which express nearly equal amounts of each protein. Small interference RNA (siRNA) technology was used to knockdown (KD) the expression of ADF and cofilin-1 independently. RESULTS: Either ADF KD or cofilin KD caused cell elongation, a reduction in cell area, a decreased ability to form invadopodia, and a decreased percentage of polarized cells after 180 s of epidermal growth factor stimulation. Moreover, ADF KD or cofilin KD increased the rate of cell migration and the time of lamellipodia protrusion but through different mechanisms: lamellipodia protrude more frequently in ADF KD cells and are more persistent in cofilin KD cells. ADF KD cells showed a significant increase in F-actin aggregates, whereas cofilin KD cells showed a significant increase in prominent F-actin bundles and increased cell adhesion. Focal adhesion area and cell adhesion in cofilin KD cells were returned to control levels by expressing exogenous cofilin but not ADF. Return to control rates of cell migration in ADF KD cells was achieved by expression of exogenous ADF but not cofilin, whereas in cofilin KD cells, expression of cofilin efficiently rescued control migration rates. CONCLUSION: Although ADF and cofilin have many redundant functions, each of these isoforms has functional differences that affect F-actin structures, cell adhesion and lamellipodial dynamics, all of which are important determinants of cell migration.
Assuntos
Actinas/metabolismo , Adenocarcinoma/metabolismo , Cofilina 1/genética , Destrina/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Mamárias Animais/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Actinas/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular , Cofilina 1/antagonistas & inibidores , Cofilina 1/metabolismo , Destrina/antagonistas & inibidores , Destrina/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Feminino , Adesões Focais/efeitos dos fármacos , Adesões Focais/metabolismo , Adesões Focais/ultraestrutura , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Metástase Neoplásica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Transdução de Sinais , Células Tumorais CultivadasRESUMO
BACKGROUND: The study was conducted to measure the extent of androgenic steroids abuse among two targeted groups in Jordan, college students and athletes, and the risk factors associated with this abuse. METHODS: Five hundred and three Jordanian collegiate students and 154 bodybuilding athletes completed a three section questionnaire that investigated demographic information, prevalence of anabolic-androgenic steroids (AAS) and attitude towards steroids abuse. RESULTS: Of the investigated collegiate students, 4.2% were current users, while the percentage rose to 26% among the athletes; the mean age of users in the two groups was 19.9 and 28.1 years, respectively. Almost one-third of the students started abusing AAS before the age of 15 years while more than half of the athletes started between the ages of 15 and 18 years. Knowing where and how to get the drugs has not been a problem for either the students or the athletes as their friends and coaches were the major sources. The main reasons for using AAS have been found to help improving athletic performance and physical appearances. CONCLUSION: Abusing AAS is starting to become a public health concern that implies the need to implement educational programmes, which will educate and warn adolescents and mentors about the negative side effects of AAS abuse on the health of users.
Assuntos
Anabolizantes , Esportes , Estudantes/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Jordânia/epidemiologia , Prevalência , Fatores de Risco , Fatores Socioeconômicos , UniversidadesRESUMO
The haplotype and allele frequency distributions of the Y-chromosomal STR markers DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, and DYS439 were determined in a sample of 97 unrelated males from Jordan.
Assuntos
Frequência do Gene , Genética Populacional , Haplótipos , Sequências de Repetição em Tandem , Cromossomos Humanos Y , Impressões Digitais de DNA , Humanos , Jordânia , Masculino , Reação em Cadeia da PolimeraseRESUMO
The efficacy of yogurt treatment against vaginal candidosis (VC) was examined using an oestrogen-dependent vaginal candidosis (EDVC) murine model. The EDVC mouse model was constructed by inoculating mice with viable Candida albicans cells under pseudo-oestrus conditions. Vaginal fungal burden in the various mouse groups was evaluated at several time points following the induction of VC. Untreated and yogurt-treated naïve mice exhibited background levels of VC (<6000 CFU per mouse). Candida albicans colonisation in untreated EDVC mice was significantly higher (P < 0.05) than that in yogurt-treated EDVC mice at days 20-30. Metronidazole-treated naïve mice developed persistent C. albicans vaginal colonisation at significantly lower levels (P < 0.05) than that in untreated or metronidazole-treated EDVC mice. Lactobacillus was only detected in the reproductive tracts of yogurt-treated naïve and EDVC mice. These findings suggest that the presence of Lactobacillus in the reproductive tract can suppress C. albicans growth and the antibiotics may predispose to VC.
Assuntos
Candidíase Vulvovaginal/terapia , Iogurte , Animais , Anti-Infecciosos/administração & dosagem , Candida albicans/crescimento & desenvolvimento , Candida albicans/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Feminino , Humanos , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/isolamento & purificação , Metronidazol/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Vagina/microbiologiaRESUMO
AIM: To establish a genetic database of the African-Jordanian population for forensic and paternity testing purposes. METHOD: Allelic distribution at fifteen short tandem repeat (STR) loci was determined for 95 healthy unrelated African-Jordanians. The 15 autosomal STR loci, included within the GenePrint PowerPlex 16 system, were amplified from the subset of the 95 DNA extracts isolated from the population sample. Electrophoresis for each polymerase chain reaction (PCR) product was carried out using the ABI Prism 310 Genetic Analyzer and the length of the amplified DNA fragments was determined using the Genotype 2.0 and PowerTyper 16 Macro softwares. Calculations of allelic frequencies, forensic efficiency parameters, Hardy-Weinberg departure, and quantitative analysis of the allele frequencies in various populations were determined. RESULTS: DNA extracts were successfully amplified and the genetic database was compiled. All tested loci showed no significant statistical deviation from Hardy-Weinberg expectations. Furthermore, no significant difference was observed between the sample population under investigation and other population genetic databases. CONCLUSION: The loci investigated here proved to be sufficiently polymorphic for forensic purposes, since the forensic efficiency values suggest that they are very discriminating in the African-Jordanian subpopulation.