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Nanomedicine has been developed to reduce or eliminate the side effects and toxicity upon systemic therapy of chemotherapeutic agents and to improve their therapeutic efficacy. However, the translation of non-sized or nano-encapsulated drugs is hampered by the low penetration and accumulation of engineered nanoparticles (NPs) in sites of tumors as well as their poor pharmacokinetics. This may be due to the synthetic structure of NPs and also complicated and unknown characteristics of the solid tumor microenvironment (TME). As a result, the TME is being better identified, and the interactions between NPs and the TME or human body are being discovered or predicted. These findings have led to the development of more biocompatible, intelligent, and controllable bio-based nanoformulations that could overcome current barriers and provide sufficient drug delivery to the TME, as discussed in this paper. These formulations are designed to (i) modify the surface of NPs to improve blood circulation while reducing their off-target accumulation and side effects in vivo, (ii) pass through the tumor vasculature by modulating or targeting angiogenesis, (iii) promote NPs distribution in solid tumor regions by applying biological/physical stimuli or extracellular matrix remodeling, and (iv) overcome the cell membrane barrier and other compartments of the cell by specific cell targeting to release the payload drug into the cytoplasm or nucleoplasm.
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Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Animais , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinéticaRESUMO
BACKGROUND: Mobile phone addiction is on the rise among various populations, particularly among the younger generations. This phenomenon can significantly impact various aspects of life, particularly mental health. This study aimed to examine the prevalence of mobile phone addiction and mental health, as well as the associated factors of mental health among medical students in southeast Iran in 2023. METHODS: Using stratified sampling, 365 students from the Kerman University of Medical Sciences were included from May to June 2023. The data collection tool comprised a questionnaire assessing general health (GHQ-28), mobile phone addiction, and social support. Logistic regression was used to examine the associated factors of mental health. RESULTS: The prevalence of mobile phone addiction and poor mental health among students was 46.6% (95% Confidence Intervals [CI]: 41.4; 51.7) and 52.9% (95% CI: 47.7; 57.9), respectively. The results of the multivariable logistic regression analysis indicated that individuals with mobile phone addiction had higher odds of experiencing a poor mental health situation (Adjusted Odds Ratio [aOR] = 2.01; 95% CI: 1.30, 3.09). Conversely, participants with higher social support scores were less likely to have poor health (aOR = 0.95; 95% CI: 0.94, 0.97). CONCLUSION: We found a high prevalence of mobile phone addiction. Considering the association between mobile phone addiction and mental health, it is necessary to prevent the complications and risks caused by mobile phone addiction; it requires educational planning, counseling, and behavior among vulnerable students.
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Comportamento Aditivo , Telefone Celular , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Irã (Geográfico)/epidemiologia , Masculino , Feminino , Prevalência , Adulto Jovem , Adulto , Telefone Celular/estatística & dados numéricos , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/psicologia , Apoio Social , Saúde Mental/estatística & dados numéricos , Estudos Transversais , Inquéritos e Questionários , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , AdolescenteRESUMO
The structural and functional disorders of the testis and ovary are one of the main complications of hyperglycemia. Betaine is a trimethyl glycine with antioxidant, antidiabetic, and anti-inflammatory potential. The aim of this study is to investigate the potential of betaine on the expression of aging and oxidative stress markers in ovarian and testicular cells under hyperglycemic conditions. Testicular and ovarian cells were subjected to four different conditions, including normal glucose and hyperglycemia, with or without betaine (5 mM). The cells with hyperglycemia saw an increase in malondialdehyde (MDA), methylglyoxal (MGO), expression of a receptor for AGE, and aging-related genes (ß-GAL), and a decrease in the activity of antioxidant enzymes including catalase, glutathione peroxidase, and superoxide dismutase. The treatment with betaine, in contrast, decreased the amount of MGO and MDA, and also downregulated aging-related signaling. Although hyperglycemia induces senescence in testicular and ovarian cells, the use of betaine may have a protective effect against the cell senescence, which may be useful in the management of infertility.
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Antioxidantes , Hiperglicemia , Masculino , Feminino , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Testículo/metabolismo , Betaína/farmacologia , Betaína/metabolismo , Ovário/metabolismo , Óxido de Magnésio/metabolismo , Estresse Oxidativo , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , beta-Galactosidase/metabolismoRESUMO
BACKGROUND: There is a dearth of robust evidence regarding the correlation between psoriasis with maternal and neonatal outcomes, making it challenging to establish definitive recommendations for the management of these patients. This systematic review and meta-analysis aimed to review the evidence with regard to the impact of maternal psoriasis on maternal and neonatal outcomes. METHODS: Following the PRISMA guideline, a systematic search of English articles using PubMed, Embase, Scopus, ScienceDirect, Web of Science, Google Scholar, and the Cochrane Library was conducted. The search was performed from inception to 22nd of May 2022. RESULT: A significant association was observed between psoriasis and maternal outcomes, including cesarean delivery [OR = 1.25 (95% CI: 1.13-1.30, p-value = 0.001)], (pre)eclampsia [OR = 1.29 (95% CI: 1.15-1.44, p-value = 0.0001)], gestational diabetes [Odds Ratio (OR) = 1.23 (95% Confidence Intervals (CI): 1.15-1.30, p-value = 0.001)], gestational hypertension [OR = 1.31 (95% CI: 1.18-1.45, p-value = 0.001)] and preterm birth [OR = 1.22 (95% CI: 1.10-1.35, p-value = 0.001)]. Also, there was a significant association between psoriasis and neonatal outcomes, including small for gestational age [OR = 1.07 (95% CI: 1.02-1.11, p-value = 0.053)], low birth weight [OR = 1.19 (95% CI: 1.02-1.38, p-value = 0.001)] and stillbirth [OR = 1.27 (95% CI: 1.04-1.55, p-value = 0.023)]. CONCLUSION: Maternal psoriasis could negatively impact maternal and neonatal outcomes. Our results strengthen the importance of close monitoring of the mothers' psoriasis status before and during pregnancy.
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Diabetes Gestacional , Pré-Eclâmpsia , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Natimorto , Diabetes Gestacional/epidemiologia , Pré-Eclâmpsia/epidemiologiaRESUMO
BACKGROUND: Hypertension (HTN) and diabetes mellitus (DM) as part of non-communicable diseases are among the most common causes of death worldwide, especially in the WHO's Eastern Mediterranean Region (EMR). The family physician program (FPP) proposed by WHO is a health strategy to provide primary health care and improve the community's awareness of non-communicable diseases. Since there was no clear focus on the causal effect of FPP on the prevalence, screening, and awareness of HTN and DM, the primary objective of this study is to determine the causal effect of FPP on these factors in Iran, which is an EMR country. METHODS: We conducted a repeated cross-sectional design based on two independent surveys of 42,776 adult participants in 2011 and 2016, of which 2301 individuals were selected from two regions where the family physician program was implemented (FPP) and where it wasn't (non-FPP). We used an Inverse Probability Weighting difference-in-differences and Targeted Maximum Likelihood Estimation analysis to estimate the average treatment effects on treated (ATT) using R version 4.1.1. RESULTS: The FPP implementation increased the screening (ATT = 36%, 95% CI: (27%, 45%), P-value < 0.001) and the control of hypertension (ATT = 26%, 95% CI: (1%, 52%), P-value = 0.03) based on 2017 ACC/AHA guidelines that these results were in keeping with JNC7. There was no causal effect in other indexes, such as prevalence, awareness, and treatment. The DM screening (ATT = 20%, 95% CI: (6%, 34%), P-value = 0.004) and awareness (ATT = 14%, 95% CI: (1%, 27%), P-value = 0.042) were significantly increased among FPP administered region. However, the treatment of HTN decreased (ATT = -32%, 95% CI: (-59%, -5%), P-value = 0.012). CONCLUSION: This study has identified some limitations related to the FPP in managing HTN and DM, and presented solutions to solve them in two general categories. Thus, we recommend that the FPP be revised before the generalization of the program to other parts of Iran.
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Diabetes Mellitus , Hipertensão , Doenças não Transmissíveis , Adulto , Humanos , Prevalência , Estudos Transversais , Médicos de Família , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Região do MediterrâneoRESUMO
Lymphatic filariasis (LF) is an important neglected parasitic disease according to the World Health Organization. In this study, we aimed to determine the prevalence of human LF in Asia using a systematic review and meta-analysis approach. Records from 1990 to 2018 in reputable databases including PubMed, Science Direct, Embase, and Cochrane Library were searched using a panel of related keywords. All 48 countries of Asia were searched one by one in combination with the keywords. In all, 41,742 cases identified in this study were included in the analysis. According to our findings, the pooled prevalence of LF in Asia was estimated at 3% (95% CI: [1.7, 5.2]). There was no major trend in the cumulative prevalence of LF over time. Some countries in Asia including China, Japan, Vietnam, and South Korea succeeded in eliminating LF as a public health problem, but others still need to monitor the disease. Based on the initiative of the WHO starting in 2000, some countries in Asia succeeded in eliminating LF as a public health problem. Other countries have taken steps to eliminate the disease with variable degrees of success. These efforts might be affected by issues such as climate change.
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Filariose Linfática/epidemiologia , Doenças Negligenciadas/epidemiologia , Ásia/epidemiologia , Erradicação de Doenças/estatística & dados numéricos , Erradicação de Doenças/tendências , Filariose Linfática/prevenção & controle , Humanos , Doenças Negligenciadas/prevenção & controle , Prevalência , Saúde Pública/estatística & dados numéricos , Saúde Pública/tendênciasRESUMO
BACKGROUND AND OBJECTIVE: We conducted this study to assess the prevalence of plagiarism and to shed light on some dark aspects of this issue. The main objectives included to find out the etiology, prevalence, and detection of various forms plagiarism. METHODS: In this Cross-sectional study we used a questionnaire, face-to-face interview, analyzing the present notifications and codes, websites, and literature review. The current study was conducted throughout Iran from 2017-2018. Those associated with scientific journalism, academic staffs, and authors were interviewed or asked to fill out a prepared questionnaire. RESULTS: Nine hundred seventy nine questionnaires were circulated. Out of this 706 (72.1%) were completed and returned. Those with a master degree were most cooperative in filling out the questionnaires (36.4%); followed by Assistant Professors (29.6%). About 74.1% of respondents, had not participated in any educational workshops on plagiarism (P<0.001) while 10.8% had not heard anything about plagiarism (P<0.001). As regards correct reply as for definition and detecting plagiarism; 91.1%, 40.8%, 48.4% and 57.9% could reply correctly (P<0.001). Forty-one-point one percent of the participants believed that reprimand would be the best punishment. The percentage of plagiarism as per people associated in journal administration, was 22.9%; based on experts' opinions, it was 30.0%; and based on analysis of some journals published in Iran, it was 25.5%. CONCLUSION: We found a noticeable prevalence of plagiarism in Iran. Many factors are involved in this misconduct; most important being the need for academic staff and students to publish e more papers regardless of their quality to meet some of the academic requirements. Considering the high rank of Iran in terms of scientific growth worldwide, it is expected from the regulatory authorities to monitor all aspects of scientific misconducts in medical journalism.
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BACKGROUND: Phakic intraocular lens (pIOL) models have indicated an association between cataract formation and inadequate vaulting. In this study, the efficacy and safety of low-vault posterior chamber pIOLs in the correction of myopia were examined over 3 years. METHODS: From 316 patients undergoing surgery, 14 eyes with a low vault (≤ 150 µm) were examined from 14 patients. After implanting the Visian Implantable Collamer pIOL for the correction of myopia (moderate and high), the pIOL vault, endothelial cell loss, uncorrected distance visual acuity (UDVA), corrected DVA (CDVA), and detrimental events were examined over 3 years. RESULTS: Based on the findings, the mean spherical equivalent reduced from - 8.15 ± 3.29 before surgery to - 1.02 ± 0.75 diopters 3 years after the surgery. In terms of visual outcomes, the mean UDVA (Log MAR) significantly increased from 0.95 ± 037 to 0.27 ± 0.28, and the mean CDVA also increased from 0.99 ± 0.11 to 0.06 ± 0.08 (P < 0.05). The mean indices of safety and efficacy were respectively 1.075 and 0.748. The eyes lost not more than two visual acuity lines. Based on the findings, 82% achieved 0.80 or better CDVA, while the total endothelial cell loss was 7.96% during 3 years. Overall, vision-threatening conditions were not reported. CONCLUSION: The introduced pIOL can be considered a safe and efficient method for myopia at moderate to high levels.
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Colágeno , Implante de Lente Intraocular/métodos , Miopia/cirurgia , Lentes Intraoculares Fácicas , Polímeros , Refração Ocular/fisiologia , Acuidade Visual , Adolescente , Adulto , Segmento Anterior do Olho/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Miopia/fisiopatologia , Estudos Prospectivos , Desenho de Prótese , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Adulto JovemRESUMO
Nicotine is a major component of tobacco plants and is responsible for the development of reproductive problems in smokers. Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS) in some parts of female reproductive system, but the effect of nicotine on endometrium that plays an important role in reproductive biology stays unexplored. The aim of this work was to clarify the direct effects of nicotine administration on the antioxidant defense system and lipid peroxidation in human endometrial cells. Human endometrial stromal primary cells were treated with nicotine (0, 10-11, 10-8, and 10-6 M) for 24 hours. On nicotine administration, the endometrial cells were associated with a decrease in antioxidant defense markers such as Glutathione (GSH) level, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) enzymes activity and higher levels of malondialdehyde (MDA) in a dose-dependent manner when compared to the control. We concluded that nicotine as a pro-oxidant affects the oxidative state of the endometrial cells.
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Endométrio/citologia , Nicotina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Adulto , Catalase/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Adulto JovemRESUMO
BACKGROUND: This paper seeks to evaluate the depth and outcomes of MyoRing implantation using two mechanical dissection procedures including: PocketMaker microkeratome in opposition to the Melles hook method. METHODS: This retrospective study was carried out on 39 eyes of 38 keratoconus patients (28 male and 10 female) with the mean age of [Formula: see text] years and had undergone MyoRing implantation by the two mentioned methods. The MyoRing was inserted into the corneal pocket which was made manually in 18 eyes (Melles hook group) or with PocketMaker microkeratome in 21 eyes (PocketMaker group). The mean follow up time was [Formula: see text] months with pre-operative and post-operative ophthalmic examination including uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), keratometry readings and central corneal thickness measurement. AS-OCT (Casia, SS-1000, Tomey, Nagoya, Japan) imaging was used to measure MyoRing insertion depth, exactly. RESULTS: Pre-operative and post-operative UCVA (LogMAR) mean change for the PocketMaker and Melles hook groups were recorded at 0.75 ± 0.32 and 0.78 ± 0.33, respectively. Similarly, BCVA (LogMAR) mean change were 0.27 ± 0.22 and 0.23 ± 0.22. Mean keratometry (Kmean) change were 6.06 ± 4.18 and 6.56 ± 3.55 respectively. UCVA change (P = 0.767), BCVA change (P = 0.77) and Kmean change (P = 0.693) showed that there was no statistically significant difference between both groups for any parameter. Depth measurements achieved from AS-OCT images showed that there was no statistically significant difference in pocket depth between two methods of MyoRing implantation (P = 0.413). CONCLUSIONS: The results of Myoring implantation outcomes using mechanical dissection via PocketMaker microkeratome as against Melles hook are comparable.
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Córnea/cirurgia , Topografia da Córnea/métodos , Ceratocone/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/instrumentação , Implantação de Prótese/instrumentação , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adolescente , Adulto , Córnea/patologia , Desenho de Equipamento , Feminino , Humanos , Ceratocone/diagnóstico , Ceratocone/fisiopatologia , Masculino , Pessoa de Meia-Idade , Próteses e Implantes , Refração Ocular , Estudos Retrospectivos , Adulto JovemRESUMO
The misinterpretation and misuse of p-value have been increasing for decades. In March 2016, the American Statistical Association released a statement to warn about the use and interpretation of p-value. In this study, we provided a definition and discussion of pvalue and emphasized the importance of its accurate interpretation.
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Due to population growth, climate change, and the urban heat island effect, heat exposure is becoming an important issue faced by urban built environments. Heat exposure assessment is a prerequisite for mitigation measures to reduce the impact of heat exposure. However, there is limited research on urban heat exposure assessment approaches that provides fine-scale spatiotemporal heat exposure information, integrated with meteorological status and human collective exposure as they move about in cities, to enable proactive heat exposure mitigation measures. Smart city digital twins (SCDTs) provide a new potential avenue for addressing this gap, enabling fine spatiotemporal scales, human-infrastructure interaction modeling, and predictive and decision support capabilities. This study aims to develop and test an SCDT for collective urban heat exposure assessment and forecasting. Meteorological sensors and computer vision techniques were implemented in Columbus, Georgia, to acquire temperature, humidity, and passersby count data. These data were then integrated into a collective temperature humidity index. A time-series prediction model and a crowd simulation were employed to predict future short-term heat exposures based on the data accumulated by this SCDT and to support heat exposure mitigation efforts. The results demonstrate the potential of SCDT to enhance public safety by providing city officials with a tool for discovering, predicting, and, ultimately, mitigating community exposure to extreme heat.
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BACKGROUND: Migraine is a common neurological disorder with a significant genetic component. Less information is known about the contribution of minor genetic variations, such as single nucleotide polymorphism (SNP) on the migraine process. In the present study, we aim to investigate the role of CACNA1A gene polymorphism on severity and related factors in family positive migraine patients. MATERIALS AND METHODS: We included 74 common migraine patients consequently. Headache severity was evaluated according to Headache Impact Test (HIT6) questionnaire and quality of life of patients was investigated according to MSQ (Migraine-Specific Quality of Life Questionnaire v2.1) questionnaire. Thirty patients with positive family history of migraine were selected and sequencing analysis after DNA extraction was performed. RESULTS: Direct sequencing revealed a known SNP G to A transition in the exon 16 (nt2369, G â A) in 9 patients. There was no significantly correlation between polymorphism and type of migraine, severity, frequency, duration and quality of life in family positive migraine. Evaluated migraine severity by HIT6 questioner couldn't act as a risk factor for this polymorphism (OR: 0.93, CI%95 0.82-1.06 P = 0.3). CONCLUSION: In Iranian population no significant association was seen between Thr698Thr (nt2369) polymorphism and head pain severity in familial migraine. Confirmation of this hypothesis needs further investigation.
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Urbanization introduces the threat of increased epidemic disease transmission resulting from crowding on mass transit. The coronavirus disease 2019 (COVID-19) pandemic, which has directly led to over 600,000 deaths in the US as of July 2021, triggered mass social distancing policies to be enacted as a key deterrent of widespread infections. Social distancing can be challenging in confined spaces required for transportation such as mass transit systems. Little is published regarding the degree to which mass transit system adoption effects impacted the rise of the COVID-19 pandemic in urban centers. Taking an ecological approach where areal data are the unit of observation, this national-scale study aims to measure the association between the adoption of mass transit and COVID-19 spread through confirmed cases in US metropolitan areas. National survey-based transit adoption measures are entered in negative binomial regression models to evaluate differences between areas. The model results demonstrate that mass transit adoption in US metropolitan areas was associated with the magnitude of outbreaks. Higher incidence of COVID-19 early in the pandemic was associated with survey results conveying higher transit use. Increasing weekly bus transit usage in metropolitan statistical areas by one scaled unit was associated with a 1.38 [95% CI: (1.25, 1.90)] times increase in incidence rate of COVID-19; a one scaled unit increase in weekly train transit usage was associated with an increase in incidence rate of 1.54 [95% CI: (1.42, 2.07)] times. These conclusions should inform early action practices in urban centers with busy transit systems in the event of future infectious disease outbreaks. Deeper understanding of these observed associations may also benefit modeling efforts by allowing researchers to include mathematical adjustments or better explain caveats to results when communicating with decision makers and the public in the crucial early stages of an epidemic.
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COVID-19 , Pandemias , Surtos de Doenças , Humanos , Incidência , SARS-CoV-2RESUMO
Antimicrobial Peptides (AMPs) have been considered as potential alternatives for infection therapeutics since antibiotic resistance has been raised as a global problem. The AMPs are a group of natural peptides that play a crucial role in the immune system in various organisms AMPs have features such as a short length and efficiency against microbes. Importantly, they have represented low toxicity in mammals which makes them potential candidates for peptide-based drugs. Nevertheless, the discovery of AMPs is accompanied by several issues which are associated with labour-intensive and time-consuming wet-lab experiments. During the last decades, numerous studies have been conducted on the investigation of AMPs, either natural or synthetic type, and relevant data are recently available in many databases. Through the advancement of computational methods, a great number of AMP data are obtained from publicly accessible databanks, which are valuable resources for mining patterns to design new models for AMP prediction. However, due to the current flaws in assessing computational methods, more interrogations are warranted for accurate evaluation/analysis. Considering the diversity of AMPs and newly reported ones, an improvement in Machine Learning algorithms are crucial. In this review, we aim to provide valuable information about different types of AMPs, their mechanism of action and a landscape of current databases and computational tools as resources to collect AMPs and beneficial tools for the prediction and design of a computational model for new active AMPs.
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Peptídeos Catiônicos Antimicrobianos , Peptídeos Antimicrobianos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bases de Dados Factuais , Aprendizado de Máquina , MamíferosRESUMO
Merkel cell polyomavirus (MCPyV) is the cause of approximately 80% of Merkel cell carcinomas (MCC). The common types of non-melanoma skin cancer (NMSC) including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are histologically similar to MCC. In the present study, 58 NMSC formalin-fixed paraffin-embedded tissue (FFPE) samples including 12 SCC, 46 BCC, and 58 FFPE samples of adjacent non-tumoral margins as the control were included. Determination of large tumor antigens (LTAg) copy number was performed by qReal-Time PCR as a viral copy number per cell to elucidate MCPyV carcinogenic role in non-melanoma skin cancer. Out of 58 samples, 36 (62%) cancerous and 22 (37.9%) normal tumor margins were positive for MCPyV LTAg. Median copy numbers of MCPyV LTAg among all NMSC samples and non-tumoral margins were 0.308×10-2 and 0.269×10-3 copies per cell respectively (P=0.001). In addition, although the viral load in the majority of samples was detected to be lower than one copy per cell, in 4 BCC samples, a viral load higher than one LTAg copy per cell was detected. The present study revealed that the detection of higher levels of MCPyV LTAg viral load in some BCC and SCC samples may be correlated with the role of MCPyV in some cases of BCC and SCC skin cancer.
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Carcinoma Basocelular , Carcinoma de Célula de Merkel , Carcinoma de Células Escamosas , Poliomavírus das Células de Merkel , Neoplasias Cutâneas , Infecções Tumorais por Vírus , Humanos , Poliomavírus das Células de Merkel/genética , Carcinoma de Célula de Merkel/patologia , Carcinoma Basocelular/genética , Carcinoma Basocelular/patologia , DNA Viral/genética , DNA Viral/análiseRESUMO
INTRODUCTION: Blood is a valuable as well as a perishable commodity that has a limited lifespan. So, keeping it in a blood bank requires careful attention and management. In this study, a management model has been designed for the blood bank that can cover all the requests sent through the hospital subunits in such a way that it has the least waste. MATERIALS AND METHODS: First, by examining the blood inventory system of a hospital, the number of inventories per month and the distribution of blood products in subunits of the hospital, and the amount of blood wastage every six months were estimated. Then, using ARENA simulation, all parts of the blood bank, including the request section, emergency blood section, donated blood section, and other sections were simulated. Finally, 10 scenarios were extracted by placing various parameters and the best scenarios were discussed and concluded. RESULTS AND DISCUSSION: The scenarios for the four blood groups included A, B, AB, and O were applied for six months in one year. The results showed that if the amount of blood injected into the blood bank is appropriate and at the right time, the amount of wastage can be reduced by up to 80% for most of the blood groups. CONCLUSION: The results of this study showed that if the system of receiving blood products built upon a precise management model is predetermined and placed with appropriate parameters, the amount of wastage will be reduced to the minimum possible number.
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Bancos de Sangue , Hospitais , HumanosRESUMO
Deubiquitinating enzymes are key regulators of the ubiquitin-proteasome system and cell cycle, and their dysfunction leads to tumorigenesis. Our in vivo drop-out screens in patient-derived xenograft models identify USP7 as a regulator of melanoma. We show that USP7 downregulation induces cellular senescence, arresting melanoma growth in vivo and proliferation in vitro in BRAF- and NRAS-mutant melanoma. We provide a comprehensive understanding of targets and networks affected by USP7 depletion by performing a global transcriptomic and proteomics analysis. We show that RRM2 is a USP7 target and is regulated by USP7 during S phase of the cell cycle. Ectopic expression of RRM2 in USP7-depleted cells rescues the senescent phenotype. Pharmacological inhibition of USP7 by P5091 phenocopies the shUSP7-induced senescent phenotype. We show that the bifunctional histone deacetylase (HDAC)/LSD1 inhibitor domatinostat has an additive antitumor effect, eliminating P5091-induced senescent cells, paving the way to a therapeutic combination for individuals with melanoma.
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Inibidores de Histona Desacetilases , Melanoma , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases , Histona Desmetilases/genética , Humanos , Melanoma/patologia , Complexo de Endopeptidases do Proteassoma , Proteínas Proto-Oncogênicas B-raf/genética , Tiofenos , Peptidase 7 Específica de Ubiquitina/metabolismo , UbiquitinasRESUMO
Green-synthesized nanobiomaterials can be engineered as smart nanomedicine platforms for diagnostic and therapeutic purposes in medicine. Herein, we investigated the bioengineering of silver nanoparticles (AgNPs) and evaluated their physicochemical, antibacterial, biofilm inhibitory, anticoagulant, and antioxidant performance. Characterization of the AgNPs was performed utilizing UV-visible, transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). The spherical shaped AgNPs were proven by TEM and SEM techniques. Moreover, the XRD diffraction patterns demonstrated that the nanoparticles were in a crystalline state. The DLS represented the hydrodynamic particle size of the NPs at 49.62 nm at a pH of 9. The calculated minimum inhibitory concentration (MIC) of AgNPs toward Staphylococcus aureus (ATCC 25923) was 8 µg mL-1, which was almost similar to tetracycline by the value of 4 µg mL-1. Moreover, the minimum bactericidal concentration (MBC) of AgNPs was 64 µg mL-1, which was significantly less than the determined value of 256 µg mL-1 for tetracycline. Considering the pathogenic and standard S. aureus, the evaluated concentrations of AgNPs and tetracycline showed significant biofilm inhibitory performance. Furthermore, the bioengineered AgNPs exhibited significant anticoagulant activity at 500 µg mL-1 compared to saline (P < 0.001). In addition, the biogenic AgNPs inhibited 69.73 ± 0.56% of DPPH free radicals at 500 µg mL-1, indicating considerable antioxidant potential.
Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/química , Antibacterianos/farmacologia , Anticoagulantes/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bioengenharia , Biofilmes , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Prata/química , Prata/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureusRESUMO
Sarcomeres are the structural units of the contractile apparatus in cardiac and skeletal muscle cells. Changes in sarcomere characteristics are indicative of changes in the sarcomeric proteins and function during development and disease. Assessment of sarcomere length, alignment, and organization provides insight into disease and drug responses in striated muscle cells and models, ranging from cardiomyocytes and skeletal muscle cells derived from human pluripotent stem cells to adult muscle cells isolated from animals or humans. However, quantification of sarcomere length is typically time consuming and prone to user-specific selection bias. Automated analysis pipelines exist but these often require either specialized software or programming experience. In addition, these pipelines are often designed for only one type of cell model in vitro. Here, we present an easy-to-implement protocol and software tool for automated sarcomere length and organization quantification in a variety of striated muscle in vitro models: Two dimensional (2D) cardiomyocytes, three dimensional (3D) cardiac microtissues, isolated adult cardiomyocytes, and 3D tissue engineered skeletal muscles. Based on an existing mathematical algorithm, this image analysis software (SotaTool) automatically detects the direction in which the sarcomere organization is highest over the entire image and outputs the length and organization of sarcomeres. We also analyzed videos of live cells during contraction, thereby allowing measurement of contraction parameters like fractional shortening, contraction time, relaxation time, and beating frequency. In this protocol, we give a step-by-step guide on how to prepare, image, and automatically quantify sarcomere and contraction characteristics in different types of in vitro models and we provide basic validation and discussion of the limitations of the software tool. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Staining and analyzing static hiPSC-CMs with SotaTool Alternate Protocol: Sample preparation, acquisition, and quantification of fractional shortening in live reporter hiPSC lines Support Protocol 1: Finding the image resolution Support Protocol 2: Advanced analysis settings Support Protocol 3: Finding sarcomere length in non-aligned cells.