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Aim: This study aims to assess the efficacy of free and niosomes-loaded paclitaxel combined with the anti-diabetic drug metformin. Methods: Paclitaxel was successfully encapsulated in all niosome formulations, using microfluidic mixing, with a maximum encapsulation efficiency of 11.9%. Results: The half maximal inhibitory concentration (IC50) for free paclitaxel in T47D cells was significantly reduced from 0.2 to 0.048 mg/ml when combined with metformin 40 mg. The IC50 of paclitaxel was significantly reduced when loaded in niosomes to less than 0.06 mg/ml alone or with metformin. Conclusion: Paclitaxel combination (free or loaded into niosomes) with metformin significantly improved the anticancer efficacy of paclitaxel, which can serve as a method to reduce the paclitaxel dose and its associated side effects.
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Metformina , Paclitaxel , Paclitaxel/farmacología , Liposomas , Composición de Medicamentos , Línea Celular TumoralRESUMEN
Background and Objectives: Venous thromboembolism is one of the leading causes of mortality and disability worldwide. Treatment with anticoagulation therapy is essential and requires a delicate approach to select the most appropriate option to improve patient outcomes, including the length of hospital stay (LOS). The aim of this study was to determine the LOS among patients with acute onset of VTE in several public hospitals in Jordan. Materials and Methods: In this study, we recruited hospitalized patients with a confirmed diagnosis of VTE. We reviewed the electronic medical records and charts of VTE admitted patients in addition to a detailed survey to collect the patients' self-reported data. Hospital LOS was categorized into three levels: 1-3 days, 4-6 days, and ≥7 days. An ordered logistic regression model was used to study the significant predictors of LOS. Results: A total of 317 VTE patients were recruited, with 52.4% of them were male and 35.3% aged between 50 and 69 years. Most patients had a deep vein thrombosis (DVT) diagnosis (84.2%), and most of the VTE cases were admitted for the first-time (64.6%). The majority of the patients were smokers (57.2%), overweight/obese (66.3%), and hypertensive (59%). Most of the VTE patients received Warfarin overlapped with low molecular weight heparins as their treatment regimen (>70%). Almost half of the admitted VTE patients (45%) were hospitalized for at least 7 days. Longer LOS was significantly associated with hypertension. Conclusions: We recommend using therapies that have been proven to reduce hospital LOS, such as non-vitamin K antagonist oral anticoagulants or direct oral anticoagulants, to treat VTE patients in Jordan. Additionally, preventing and controlling comorbidities such as hypertension is essential.
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Hipertensión , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Estudios Transversales , Jordania/epidemiología , Tiempo de Internación , Embolia Pulmonar/terapia , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/prevención & control , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/epidemiologíaRESUMEN
Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.
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BACKGROUND: To date, there is no effective treatment for COVID-19. Vaccines are effective and safe strategies to control the pandemic. OBJECTIVE: To measure consumers' maximum willingness to pay (WTP) for COVID-19 vaccines in Jordan and to identify the predictors of WTP. METHOD: An online survey was used to collect data related to sociodemographic factors and constructs from the Health Belief Model (HBM). The contingent valuation method using the payment card approach was used, whereby the respondents were asked to choose their maximum WTP value from a range of 5-200 Jordanian Dinar (JOD). The maximum WTP values were then categorized into several groups, and an ordered logistic model was used to generate adjusted odds ratios and estimate the significant predictors of maximum WTP. RESULTS: A total of 3116 respondents completed the survey. More than half of the sample were not willing to pay out of pocket for the vaccine (57%). Among the respondents who were willing to pay any amount above zero, the mean maximum WTP was 28.1 JOD (39.63 USD), and the median WTP was 20 JOD (28.21 USD). The significant predictors of higher WTP values were being of younger age, higher income, being a healthcare provider, having one or more chronic diseases, previous history of receiving the seasonal influenza vaccine, having a family member/friend who has died from the COVID-19, lower perceived risk of the vaccine, higher perceived benefits of the vaccine, and having been recommended to get the vaccine. CONCLUSION: It is recommended to continue providing the vaccine free of charge to increase its uptake. Educational campaigns should focus on refuting myths related to the vaccine and promoting the benefits of receiving the vaccine in slowing the spread of the pandemic, and improving the economy. Healthcare providers' recommendations have the potential to increase WTP for the vaccine.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Modelo de Creencias sobre la Salud , Encuestas y CuestionariosRESUMEN
Substance abuse is a worldwide problem with serious repercussions for patients and the communities where they live. Pregabalin (Lyrica), is a medication commonly used to treat neuropathic pain. Like other analgesic medications there has been concern about pregabalin abuse and misuse. Although it was initially suggested that pregabalin, like other gabapentinoids, has limited abuse liability, questions still remain concerning this inquiry. Changes in glutamate system homeostasis are a hallmark of adaptations underlying drug dependence, including down-regulation of the glutamate transporter 1 (GLT-1; SLC1A2) and the cystine/glutamate antiporter (xCT; SLC7A11). In this study, it was found that pregabalin (90 mg/kg) produces a conditioned place preference (CPP), indicative of reinforcing effects that suggest a potential for abuse liability. Moreover, like other drugs of abuse, pregabalin also produced alterations in glutamate homeostasis, reducing the mRNA expression of Slc1a2 and Slc7a11 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Amoxicillin clavulanic acid, a ß-lactam antibiotic, blocked the reinforcing effects of pregabalin and normalized glutamate homeostasis. These results suggest that pregabalin has abuse potential that should be examined more critically, and that, moreover, the mechanisms underlying these effects are similar to those of other drugs of abuse, such as heroin and cocaine. Additionally, these results support previous findings showing normalization of glutamate homeostasis by ß-lactam drugs that provides a novel potential therapeutic approach for the treatment of drug abuse and dependence.
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Combinación Amoxicilina-Clavulanato de Potasio , Trastornos Relacionados con Sustancias , Humanos , Combinación Amoxicilina-Clavulanato de Potasio/metabolismo , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Pregabalina/farmacología , Núcleo Accumbens , Trastornos Relacionados con Sustancias/metabolismo , Transportador 2 de Aminoácidos Excitadores/metabolismo , beta-Lactamas/farmacología , Glutamatos/metabolismo , Glutamatos/farmacología , Ácido Glutámico/metabolismoRESUMEN
In men, prostate cancer (PC) is the most frequently diagnosed cancer, causing an estimated 375,000 deaths globally. Currently, existing therapies for the treatment of PC, notably metastatic cases, have limited efficacy due to drug resistance and problematic adverse effects. Therefore, it is imperative to discover and develop novel drugs for treating PC that are efficacious and do not produce intolerable adverse or toxic effects. Condensed quinolines are naturally occurring anticancer compounds. In this study, we determined the in vitro efficacy of IND-2 (4-chloro-2-methylpyrimido[1â³,2â³:1,5]pyrazolo[3,4-b]quinolone) in the PC lines, PC-3 and DU-145. IND-2 significantly inhibited the proliferation of PC-3 and DU-145, with IC50 values of 3 µM and 3.5 µM, respectively. The incubation of PC-3 cells with 5 and 10 µM of IND-2 caused the loss of the mitochondrial membrane potential in PC-3 cells. Furthermore, IND-2, at 5 µM, increased the expression of cleaved caspase-3, cleaved caspase-7 and cleaved poly (ADP-ribose) polymerase (PARP). The incubation of PC-3 cells with 5 µM of IND-2 significantly decreased the expression of the apoptotic protein, B-cell lymphoma 2 (Bcl-2). Furthermore, 5 and 10 µM of IND-2 produced morphological changes in PC-3 cells characteristic of apoptosis. Interestingly, IND-2 (2.5, 5 and 10 µM) also induced mitotic catastrophe in PC-3 cells, characterized by the accumulation of multinuclei. The incubation of DU-145 cells with 1.25 and 5 µM of IND-2 significantly increased the levels of reactive oxygen species (ROS). Finally, IND-2, at 10 µM, inhibited the catalytic activity of topoisomerase IIα. Overall, our findings suggest that IND-2 could be a potential lead compound for the development of more efficacious compounds for the treatment of PC.
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Lipid nanoparticles have gained much attention due to their potential as drug delivery systems. They are safe, effective, and be targeted to particular tissues to deliver their payload. Niosomes are one type of lipid nanoparticles that comprise non-ionic surfactants which have proven to be effective due to their stability and biocompatibility. Different manufacturing processes have been reported for niosome preparation, but many of them are not scalable or reproducible for pharmaceutical use. In this study, microfluidic mixing was used to prepare niosomes with different lipid compositions by changing the type of non-ionic surfactant. Niosomes were evaluated for their physicochemical characteristics, morphology, encapsulation efficacy, release profiles of atenolol as a model hydrophilic compound, and cytotoxic activities. Microfluidic mixing allows for particle self-assembly and drug loading in a single step, without the need for post-preparation size reduction. Depending on the lipid composition, the empty particles were <90 nm in size with a uniform distribution. A slight but not significant increase in these values was observed when loading atenolol in most of the prepared formulations. All formulations were spherical and achieved variable levels of atenolol encapsulation. Atenolol release was slow and followed the Korsmeyer-Peppas model regardless of the surfactant type or the percentage of cholesterol used.
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The detection of >400 Monkeypox virus cases in the month of May 2022 and increase to 57,527. confirmed cases by September 9th, 2022, across the world, emphasizes the need of new therapeutics for this emerging viral epidemic in humans. Largely the cases seen in Europe, Australia and America are among men who have sex with men making transmission through intimate contact with infectious skin lesions the likely mode of transmission. This implies that this high human-to-human transmission observed in the young Caucasian clusters, and the probable community transmission without any history of travelling to endemic areas would suggest that the epidemic is likely to be sustained human-to-human transmission and unlikely one that would be a short-lasting epidemic. This might necessitate the need for new therapeutic approaches and agents for prophylaxis and treatment of acute infections which is the focus of this review article.
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Mpox , Minorías Sexuales y de Género , Vacunas , Masculino , Humanos , Mpox/tratamiento farmacológico , Mpox/epidemiología , Mpox/prevención & control , Antivirales/uso terapéutico , Homosexualidad MasculinaRESUMEN
Chronic tobacco exposure can alter the endocannabinoid (eCB) system, consequently leading to an anxiety state. In this study, we investigated the effects of waterpipe tobacco smoke (WTS) on cannabinoid receptor 1 and 2 (CBR1 and CBR2) gene and protein expression in mesocorticolimbic brain regions. Using elevated plus maze (EPM) and open field (OF) tests, the effects of WTS exposure on withdrawal-induced anxiety-like behavior were examined. The effect of ceftriaxone (CEF), a ß-lactam known to upregulate glutamate transporter 1 (GLT-1), on anxiety and the expression of cannabinoid receptors was also determined. Male Sprague-Dawley rats were randomly assigned to four groups: 1) the Control group was exposed only to standard room air; 2) the WTS group was exposed to tobacco smoke and treated with saline vehicle; 3) the WTS-CEF group was exposed to WTS and treated with ceftriaxone; and 4) the CEF group was exposed only to standard room air and treated with ceftriaxone. Rats were exposed to WTS (or room air) for two hours per day, five days per week for a period of four weeks. Behavioral tests (EPM and OF) were conducted weekly during acute withdrawal, 24 h following WTS exposure. Rats were given either saline or ceftriaxone (200 mg/kg i.p.) for five days during Week 4, 30 min prior to WTS exposure. Withdrawal-induced anxiety was induced by WTS exposure but was reduced by ceftriaxone treatment. WTS exposure decreased CBR1 mRNA and protein expression in the NAc and VTA, but not PFC, and ceftriaxone treatment attenuated these effects. WTS exposure did not change CBR2 mRNA expression in the NAc, VTA, or PFC. These findings demonstrate that WTS exposure dysregulated the endocannabinoid system and increased anxiety-like behavior, and these effects were reversed by ceftriaxone treatment, which suggest the involvement of glutamate transporter 1 in these effects.
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Ceftriaxona , Tabaco para Pipas de Agua , Sistema de Transporte de Aminoácidos X-AG/metabolismo , Animales , Encéfalo/metabolismo , Ceftriaxona/farmacología , Endocannabinoides , Transportador 2 de Aminoácidos Excitadores/metabolismo , Masculino , ARN Mensajero , Ratas , Ratas Sprague-Dawley , Humo/efectos adversos , Nicotiana/metabolismoRESUMEN
Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems. Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior. Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days. Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression. Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.
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BACKGROUND: The use of health-related applications (apps) on smartphones has become widespread. This is especially of value during the ongoing SAR-COV-2 pandemic, where accessibility to health care services has been greatly limited. Patients with free access to apps can obtain information to improve their understanding and management of health issues. Currently, there are cancer-related apps available on iPhones and androids. However, there are no guidelines to control these apps and ensure their quality. Furthermore, these apps may significantly modify the patients' perception and knowledge about drug-related health services. OBJECTIVES: The aim of this study was to assess the convenience, quality, safety and efficacy of apps for cancer patient care. METHODS: The study was conducted by searching all apps related to cancer care on both Google Play Store and Apple iTunes Store. A detailed assessment was then performed using the mobile application rating scale (MARS) and risk assessment tools. RESULTS: The results indicated that on a scale from 1-5, 47% of the apps were rated ≥ 4. The MARS assessment of the apps yielded an overall quality rating of 3.38 ± 0.9 (mean ± SD). The visual appeal of the app was found to have a significant effect on app functionality and user engagement. The potential benefits of these apps come with challenges and limitations. Patents related to smartphone applications targeting patients were also discussed. CONCLUSION: We recommend a greater emphasis toward producing evidence-based apps. These apps should be rigorously tested, evaluated and updated by experts, particularly clinical pharmacists. Also, these apps may alter patient attitudes toward services provided by physicians and pharmacists. Finally, these apps should not replace in-person interactive health services.
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COVID-19 , Aplicaciones Móviles , Neoplasias , Humanos , Neoplasias/terapia , Patentes como Asunto , Atención al Paciente , Teléfono InteligenteRESUMEN
AIM OF STUDY: Urinary tract infections (UTIs) are among the most common infections affecting individuals of different ages worldwide. Antimicrobial agents are usually the first-line treatment for UTIs, and the use of the prescribed antibiotic is escalating, resulting in increased rates of bacterial resistance and UTI recurrence. The current study aimed to identify the causative bacteria in Jordan, to explore their resistance pattern to antibiotics and to describe drug-related problems (DRPs) associated with UTI management. METHODS: This prospective, descriptive study was conducted in two major health institutions in two cities in Jordan over a period of six months. The study population included inpatients and outpatients diagnosed with UTIs. Patients' data were collected directly from patients using data collection sheet and from patients' charts. RESULTS: A total of 273 patients were included, of whom 56.4% were women. Urine cultures were obtained from 81% of the patients. Escherichia coli was the most common causative pathogen (50.6%), followed by Klebsiella pneumonia (10.8%). Extended spectrum beta-lactamase (ESBL) producing E. coli was the most commonly detected organism across all types of UTIs. Ceftriaxone and imipenem/cilastatin were most commonly administered to hospitalised patients, whilst ciprofloxacin and co-triamzaxole were the most commonly prescribed in outpatient clinics. The susceptibility results for parenteral antibiotics showed high rates of resistance to cefazolin and ticarcillin. Additionally, high rates of resistance to fluoroquinolones were identified. Further, several DRPs were identified. High rates of resistance to commonly prescribed antibiotics were detected. DRPs (ie, inappropriate antibiotic dosage, unnecessary antibiotic prescribing, inappropriate duration of therapy and prescribing of ineffective antibiotics) were relatively common. CONCLUSION: The present study highlights the need for clinical pharmacists to manage the high level of drug related problems by providing updated information about proper drug selection, rational drug use and patient education and counselling.
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Infecciones por Escherichia coli , Infecciones Urinarias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Infecciones Urinarias/tratamiento farmacológico , beta-LactamasasRESUMEN
OBJECTIVES: To assess the knowledge about cervical cancer and HPV infection and the awareness towards and perceived barriers of HPV vaccination amid medical students in Jordan. METHODS: The present study is a cross-sectional survey that was conducted for a period of three months in the College of Medicine at six different universities in Jordan. Third-year to sixth-year students from these medical colleges in Jordan were invited to participate in the study. RESULTS: There were 504 students that took part in the study with 42.3% being males and 57.7% females. The mean knowledge score of students in our survey was 21.4 ± 4.4 out of 34, which was categorized as a moderate level of knowledge regarding cervical cancer and HPV. Only 40.5% knew about the availability of the HPV vaccine in Jordan, and 65.9% accepted the idea that it is necessary to introduce the HPV vaccine for school girls in Jordan. CONCLUSIONS: This study highlights that there is inadequate knowledge about cervical cancer and its screening among medical students in Jordan. Despite the limited awareness about the HPV vaccine among the study's participants, there is a favorable opinion towards the introduction of the vaccine for school girls in Jordan. The data provide a benchmark on the level of knowledge about cervical cancer and awareness about HPV, which can be used to formulate an effective awareness program.
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Flavonoids have been shown to have antioxidant, anti-inflammatory, anti-proliferative, antibacterial and antiviral efficacy. Therefore, in this study, we choose 85 flavonoid compounds and screened them to determine their in-silico interaction with protein targets crucial for SARS-CoV-2 infection. The five important targets chosen were the main protease (Mpro), Spike receptor binding domain (Spike-RBD), RNA - dependent RNA polymerase (RdRp or Nsp12), non-structural protein 15 (Nsp15) of SARS-CoV-2 and the host angiotensin converting enzyme-2 (ACE-2) spike-RBD binding domain. The compounds were initially docked at the selected sites and further evaluated for binding free energy, using the molecular mechanics/generalized Born surface area (MMGBSA) method. The three compounds with the best binding scores were subjected to molecular dynamics (MD) simulations. The compound, tribuloside, had a high average binding free energy of -86.99 and -88.98 kcal/mol for Mpro and Nsp12, respectively. The compound, legalon, had an average binding free energy of -59.02 kcal/mol at the ACE2 spike-RBD binding site. The compound, isosilybin, had an average free binding energy of -63.06 kcal/mol for the Spike-RBD protein. Overall, our results suggest that tribuloside, legalon and isosilybin should be evaluated in future studies to determine their efficacy to inhibit SARS-CoV-2 infectivity.
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COVID-19 , SARS-CoV-2 , Flavonoides , Humanos , Simulación del Acoplamiento Molecular , Unión Proteica , Glicoproteína de la Espiga del CoronavirusRESUMEN
RNA interference (RNAi) is a posttranscriptional regulatory mechanism that employs siRNA. It typically results in the degradation of a target mRNA that encodes a particular protein. Treatment with siRNA therapeutics requires the use of an effective drug delivery system to assist in delivering these therapeutics into the cytoplasm of the transfected cells. Here we describe the transfection of melanoma cancer cells with siRNA using cationic niosome nanoparticles as a delivery system. The method of niosome preparation is first introduced and is followed by complex formation with siRNA and the transfection method.
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Melanoma , Nanopartículas , ARN Interferente Pequeño , Transfección , Humanos , Liposomas , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Melanoma/terapia , Nanopartículas/química , Nanopartículas/uso terapéutico , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacologíaRESUMEN
Melanoma accounts for 4% of all skin cancer malignancies, with only 14% of diagnosed patients surviving for more than 5 years after diagnosis. Until now, there is no clear understanding of the detailed molecular contributors of melanoma pathogenesis. Accordingly, more research is needed to understand melanoma development and prognosis.All the treatment approaches that are currently applied have several significant limitations that prevent effective use in melanoma. One major limitation in the treatment of cancer is the acquisition of multidrug resistance (MDR). The MDR results in significant treatment failure and poor clinical outcomes in several cancers, including skin cancer. Treatment of melanoma is especially retarded by MDR. Despite the current advances in targeted and immune-mediated therapy, treatment arms of melanoma are severely limited and stand as a significant clinical challenge. Further, the poor pharmacokinetic profile of currently used chemotherapeutic agents is another reason for treatment failure. Therefore, more research is needed to develop novel drugs and carrier tools for more effective and targeted treatment.Nucleic acid therapy is based on nucleic acids or chemical compounds that are closely related, such as antisense oligonucleotides, aptamers, and small-interfering RNAs that are usually used in situations when a specific gene implicated in a disorder is deemed a therapeutically beneficial target for inhibition. However, the proper application for nucleic acid therapies is hampered by the development of an effective delivery system that can maintain their stability in the systemic circulation and enhance their uptake by the target cells. In this chapter, the prognosis of the different types of melanoma along with the currently used medications is highlighted, and the different types of nucleic acids along with the currently available nanoparticle systems for delivering these nucleic acids into melanoma cells are discussed. We also discuss recently conducted research on the use of different types of nanoparticles for nucleic acid delivery into melanoma cells and highlight the most significant outcomes.
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Antineoplásicos , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Melanoma/tratamiento farmacológico , Nanopartículas , Ácidos Nucleicos , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Múltiples Medicamentos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Nanopartículas/química , Nanopartículas/uso terapéutico , Ácidos Nucleicos/química , Ácidos Nucleicos/farmacología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
Zebrafish is now among the leading in vivo model for cancer research, including prostate cancer. They are an alternative economic model being used to study cancer development, proliferation, and metastasis. They can also be effectively utilized for the development of cancer drugs at all levels, including target validation, and high-throughput screening for possible lead molecules. In this review, we provide a comprehensive overview of the role of zebrafish as an in vivo model in prostate cancer research. Globally, prostate cancer is a leading cause of death in men. Although many molecular mechanisms have been identified as playing a role in the pathogenesis of prostate cancer, there is still a significant need to understand the initial events of the disease. Furthermore, current treatments are limited by the emergence of severe toxicities and multidrug resistance. There is an essential need for economical and relevant research tools to improve our understanding and overcome these problems. This review provides a comprehensive summary of studies that utilized zebrafish for different aims in prostate cancer research. We discuss the use of zebrafish in prostate cancer cell proliferation and metastasis, defining signaling pathways, drug discovery and therapeutic development against prostate cancer, and toxicity studies. Finally, this review highlights limitations in this field and future directions to efficiently use zebrafish as a robust model for prostate cancer therapeutics development.
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Antineoplásicos/farmacología , Modelos Animales de Enfermedad , Neoplasias de la Próstata/patología , Animales , Proliferación Celular/fisiología , Desarrollo de Medicamentos , Descubrimiento de Drogas/métodos , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/tratamiento farmacológico , Pruebas de Toxicidad/métodos , Pez CebraRESUMEN
BACKGROUND: Colorectal cancer is one of the most common types of cancer worldwide and a leading cause of death in Jordan. BCL-2 and MCL-1 are anti-apoptotic proteins that inhibit programmed cell death and their over-expression has been shown to be associated with reduced sensitivity to chemotherapy and poor survival in cancer patients. OBJECTIVES: In the present study, three SNPs in the promoter region of antiapoptotic genes were investigated in an effort to inspect the occurrences of SNPs (rs2279115, rs4987852) in the promoter region of BCL2 and SNP (rs9803935) in the promoter region of MCL1 in Jordanian patients with CRC, and investigate correlations between BCL2 and MCL1 SNPs and clinical outcomes. METHODS: PCR-restriction fragment length polymorphism (RFLP)-based analysis was used for samples genotyping. RESULTS: The BCL2 rs2279115 and MCL1 rs9803935 SNPs showed significant distribution where mutant and hetero genotypes are more prominent in CRC patients. Additionally, the rs2279115 genotypes and alleles were associated with stages of disease, its recurrence and metastasis. The MCL1 rs9803935 genotypes were associated disease metastasis. However, for BCL2 rs4987852 SNP, there was no association of genotypes or alleles with any of the disease variables. CONCLUSION: The BCL2 SNPs (rs2279115) and MCL1 SNP (rs9803935) present as important determinants of the progress of CRC in Jordanian patients.
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Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Anciano , Alelos , Proteínas Reguladoras de la Apoptosis/genética , Femenino , Genotipo , Humanos , Jordania , Masculino , Persona de Mediana EdadRESUMEN
At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.
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Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Vacunas Virales , Antivirales/uso terapéutico , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Técnicas de Laboratorio Clínico , Coronavirus/genética , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Progresión de la Enfermedad , Humanos , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Neumonía Viral/terapia , ARN Viral , SARS-CoV-2 , Vacunas Virales/genética , Vacunas Virales/inmunología , Tratamiento Farmacológico de COVID-19RESUMEN
Flavonoids are low molecular weight, polyphenolic phytochemicals, obtained from secondary metabolism of various plant compounds. They have a spectrum of pharmacological efficacies, including potential anticancer efficacy. Natural flavonoids are present in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. Flavonoids can attenuate or inhibit the initiation, promotion and progression of cancer by modulating various enzymes and receptors in diverse pathways that involve cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis and metastasis. Furthermore, in vitro, flavonoids have been shown to reverse multidrug resistance when used as chemo-adjuvants. Flavonoids (both natural and synthetic analogues) interact with several oncogenic targets through dependent and independent mechanisms to mediate their anticancer efficacy in different types of cancer cells.