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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38446742

RESUMO

Bioinformatics has revolutionized biology and medicine by using computational methods to analyze and interpret biological data. Quantum mechanics has recently emerged as a promising tool for the analysis of biological systems, leading to the development of quantum bioinformatics. This new field employs the principles of quantum mechanics, quantum algorithms, and quantum computing to solve complex problems in molecular biology, drug design, and protein folding. However, the intersection of bioinformatics, biology, and quantum mechanics presents unique challenges. One significant challenge is the possibility of confusion among scientists between quantum bioinformatics and quantum biology, which have similar goals and concepts. Additionally, the diverse calculations in each field make it difficult to establish boundaries and identify purely quantum effects from other factors that may affect biological processes. This review provides an overview of the concepts of quantum biology and quantum mechanics and their intersection in quantum bioinformatics. We examine the challenges and unique features of this field and propose a classification of quantum bioinformatics to promote interdisciplinary collaboration and accelerate progress. By unlocking the full potential of quantum bioinformatics, this review aims to contribute to our understanding of quantum mechanics in biological systems.


Assuntos
Metodologias Computacionais , Teoria Quântica , Algoritmos , Biologia Computacional , Desenho de Fármacos
2.
J Cell Mol Med ; 27(16): 2278-2289, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37487022

RESUMO

MIR100HG is a long non-coding RNA (lncRNA) encoded by a locus on chr11:122,028,203-122,556,721. This gene can regulate cell proliferation, apoptosis, cell cycle transition and cell differentiation. MIR100HG was firstly identified through a transcriptome analysis and found to regulate differentiation of human neural stem cells. It is functionally related with a number of signalling pathways such as TGF-ß, Wnt, Hippo and ERK/MAPK signalling pathways. Dysregulation of MIR100HG has been detected in a diversity of cancers in association with clinical outcomes. Moreover, it has a role in the pathophysiology of dilated cardiomyopathy, intervertebral disk degeneration and pulmonary fibrosis. The current study summarizes the role of these lncRNAs in human disorders.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , Ciclo Celular , Proliferação de Células/genética , Neoplasias/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , MicroRNAs/genética
3.
J Med Virol ; 95(3): e28607, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36815507

RESUMO

Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.


Assuntos
COVID-19 , Vacinas , Humanos , COVID-19/prevenção & controle , Irã (Geográfico)/epidemiologia , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos de Coortes , Unidades de Terapia Intensiva
4.
Genomics ; 114(1): 253-265, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34923090

RESUMO

Omics data integration plays an essential role in manifesting hidden cancer insights. To detect the main combinatorial/parallel impact of cancer events, integrative approaches in pan-cancer studies must be used. Here, we assessed gastrointestinal (GI) cancers from several perspectives of genomics, transcriptomics, epigenomics, and also combinatorial impacts using a novel integrative approach to score genes. Next, scores were diffused on a signaling network and extracted subnetworks. We also implemented our new scoring method to compare upper-/lower-GI cancers, investigate the regulatory mechanisms of lncRNAs, and detect amplifications/deletions between GI and non-GI cancers. The integrative subnetwork indicated the interplay among essential protein families in the cell cycle. The copy-number-variation-related subnetwork revealed minor cell cycle and immune effects, whereas the methylation-related subnetwork revealed significant immune effects. The top-score lncRNAs indicated a distinct regulatory pattern for lower-/upper-, and accessory-GI categories. In summary, cell cycle dysfunction might be largely the consequence of combinatorial abnormalities.


Assuntos
Neoplasias Gastrointestinais , Projetos de Pesquisa , Ciclo Celular/genética , Variações do Número de Cópias de DNA , Epigenômica , Neoplasias Gastrointestinais/genética , Humanos
5.
Cancer Cell Int ; 22(1): 270, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042493

RESUMO

Long Intergenic Non-Protein Coding RNA 1133 (LINC01133) is a long non-coding RNA (lncRNA) which interacts with miR-106a-3p, miR-576-5p, miR-495-3p, miR-205, miR-199a-5p, miR-4784, miR-30a-5p, miR-199a, miR-30b-5p, miR-216a -5p and miR-422a, thus increasing expression of mRNA targets of these miRNAs. LINC01133 can affect cancer metastasis through regulation of epithelial-mesenchymal transition program. Dysregulation of this lncRNA has been repeatedly detected in the process of tumorigenesis. In this review, we summarize the results of various studies that reported dysregulation of LINC01133 in different samples and described the role of this lncRNA as a marker for these disorders.

6.
Cancer Cell Int ; 22(1): 378, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457039

RESUMO

Membrane vesicles having a diameter of 30-150 nm are known as exosomes. Several cancer types secrete exosomes, which may contain proteins, circular RNAs (circRNAs), microRNAs, or DNA. CircRNAs are endogenous RNAs that do not code for proteins and can create continuous and covalently closed loops. In cancer pathogenesis, especially metastasis, exosomal circRNAs (exo-circRNAs) have a crucial role mainly due to the frequently aberrant expression levels within tumors. However, neither the activities nor the regulatory mechanisms of exo-circRNAs in advancing lung cancer (LC) are obvious. A better understanding of the regulation and network connections of exo-circRNAs will lead to better treatment for LCs. The main objective of the current review is to highlight the functions and mechanisms of exo-circRNAs in LC and assess the relationships between exo-circRNA dysregulation and LC progression. In addition, underline the possible therapeutic targets based on exo-circRNA modulating.

7.
Crit Care ; 24(1): 171, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326981

RESUMO

BACKGROUND: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output < 0.5 ml/kg/h) in acutely ill patients and its association with the need for renal replacement therapy (RRT) and outcome. METHODS: International observational study. All adult (> 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. RESULTS: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient-oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged-oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent-oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). CONCLUSIONS: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.


Assuntos
Estado Terminal/terapia , Mortalidade , Oligúria/etiologia , Oligúria/mortalidade , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Substituição Renal/tendências , Estatísticas não Paramétricas
8.
Eur J Clin Pharmacol ; 76(4): 491-499, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31900543

RESUMO

PURPOSE: Delirium is reported in over 50% of critically ill ICU patients, and is associated with increased mortality and long-term cognitive consequences. Prevention and early management of delirium are essential components of ICU care. However, pharmacological interventions have not been effective in delirium prevention. This study investigated the effect of aripiprazole in the prevention of delirium in a neurosurgical intensive care unit. METHODS: In this prospective, randomized placebo-controlled small clinical trial, 53 patients, 18 to 80 years old, were randomized to receive enteric aripiprazole (15 mg) or placebo for up to 7 days. Delirium, detected by the Confusion Assessment Method-ICU, ICU events, laboratory studies, aripiprazole safety, time to delirium onset, delirium-free days, delirium prevalence during follow-up and ICU length of stay were recorded. RESULTS: Forty patients with similar baseline characteristics, including age, sex, neurosurgery types and APACHE II scores, completed the study. Delirium incidence and the mean days to its onset were 20% vs. 55% (p = 0.022) and 2.17 ± 0.41 vs. 2.09 ± 0.30 (p = 0.076) in the aripiprazole and placebo groups, respectively. The mean number of delirium-free days were: 5.6 (95%CI, 4.6-6.5) and 4.3 (95%CI, 3.2-5.4), in aripiprazole and placebo groups, respectively (p = 0.111). The prevalence of delirium during the follow-up was significantly lower in the aripiprazole group (p = 0.018). Serious aripiprazole adverse reactions were not observed. CONCLUSIONS: Aripiprazole can reduce the incidence of delirium in the neurosurgical ICU. Studies with larger sample size in diverse ICU settings and longer follow-up are needed to confirm our findings.


Assuntos
Aripiprazol/uso terapêutico , Delírio/prevenção & controle , Procedimentos Neurocirúrgicos , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , APACHE , Adulto , Aripiprazol/administração & dosagem , Aripiprazol/efeitos adversos , Estado Terminal , Método Duplo-Cego , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Agonistas do Receptor 5-HT1 de Serotonina/efeitos adversos , Resultado do Tratamento
9.
J Clin Pharm Ther ; 44(5): 780-787, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254478

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Fingerprinting is recognized as an easily accessible means of personal identification; however, fingerprints can be damaged after administration of some chemotherapy agents that result in hand and foot syndrome (HFS). Fingerprint loss may also be due to reasons unrelated to HFS. This study evaluated the incidence of fingerprint changes in patients treated with capecitabine-containing chemotherapy regimens and its relations to various grades of HFS. METHODS: Seventy-one patients who received chemotherapy with or without capecitabine as part of their regimen were enrolled in the study. Fingerprints were collected once before the initiation of chemotherapy and once after the third course of chemotherapy. The fingerprints were examined by the Iranian Society of Forensic Physicians, for probable changes in the post-chemotherapy states. RESULTS AND DISCUSSION: Thirty-seven patients were enrolled in the capecitabine group and 34 in a comparison group. Fingerprint changes were observed in 25 (67.6%) of the 37 patients in the capecitabine group and none in the comparison group. There was no correlation between the occurrence or severity of HFS and fingerprint changes (P = 0.880). In capecitabine group, the total dose and course numbers of capecitabine were not significant in patients with and without fingerprint changes. WHAT IS NEW AND CONCLUSION: Based on our findings, we recommend notifying patients who are considered for capecitabine therapy about the risk of fingerprint changes before the initiation of treatment, as this may have legal implications.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Capecitabina/uso terapêutico , Adulto , Idoso , Feminino , Síndrome Mão-Pé/tratamento farmacológico , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade
10.
Iran J Med Sci ; 41(3 Suppl): S31, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27840497

RESUMO

BACKGROUND: Gingivitis is an inflammatory disease involving the gums. Saffron contains various forms of flavonoids, glycosides, and anthocyanin compounds that are proven to have anti-inflammatory and antioxidant effects. This study evaluates the anti-inflammatory effects of Saffron stigma on gingival indices in patients with marginal generalized plaque-induced gingivitis. METHODS: For this study, we used toothpaste containing aqueous extract of Saffron stigma. Twenty-two patients with generalized marginal gingivitis were selected. Patients were randomly divided into two equal groups of test and placebo. In each group the pocket depth index (PD), gingival index (GI), plaque index (PI) and bleeding of probing index (BOP) were measured before and one month after use. Independent t-test, Mann-Whitney test and Wilcoxon test were used for statistical analysis (P<0.05). RESULTS: The comparison between gingival indices before and one month after toothpaste usage showed a significant decrease in some measured indices at the end of the study. Saffron stigma treated group had a significant difference in reducing GI and BOP indices in comparison with the placebo group (P<0.05). However, the difference for PD and PI indices was not statistically significant (P>0.05). CONCLUSION: In this study, it was found that using aqueous extract of Saffron stigma flower containing toothpaste might have a positive effect on some gingival indices in patients with gingivitis.

11.
Ann Pharmacother ; 48(6): 796-800, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24615628

RESUMO

OBJECTIVE: Chemotherapy with oxaliplatin is used for a wide range of malignancies. Unlike other platinum derivatives, oxaliplatin has less nephrotoxicity. However, in recent years, there have been multiple reports of different forms of renal toxicity related to this agent. CASE SUMMARY: A 40-year-old woman with colon adenocarcinoma developed jaundice, hematuria, and oliguria after the 36th cycle of oxaliplatin chemotherapy. Laboratory data revealed severe anemia, thrombocytopenia, increased creatinine, indirect hyperbilirubinemia, and high lactate dehydrogenase. A negative direct antiglobulin test and presence of <1% schistocytes in the peripheral blood smear stood against the diagnosis of immune-mediated hemolytic anemia or hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Renal biopsy was consistent with interstitial nephritis with tubular vacuolization in favor of drug-induced renal injury. Based on the Naranjo Probability Scale, the likelihood of oxaliplatin-induced renal injury in this case was probable. DISCUSSION: To our knowledge, this is the first case report of renal tubular vacuolization with symptoms mimicking thrombotic microangiopathy in a patient on long-term chemotherapy with oxaliplatin. CONCLUSIONS: Oxaliplatin can induce various forms of nephrotoxicity such as renal tubular vacuolization, acute tubular necrosis, renal tubular acidosis, and acute kidney injury secondary to hematological toxicity. Monitoring for renal function abnormalities and hemolysis should be considered during oxaliplatin-based chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Nefropatias/induzido quimicamente , Compostos Organoplatínicos/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adulto , Neoplasias do Colo/tratamento farmacológico , Feminino , Humanos , Rim/patologia , Nefropatias/patologia , Oxaliplatina
12.
Sci Total Environ ; 924: 171261, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417520

RESUMO

The recent scientific focus on polycyclic aromatic hydrocarbons (PAHs) has stemmed from their recognized genotoxic, mutagenic, and carcinogenic properties. This systematic review seeks to evaluate the nexus between exposure to water sources contaminated with PAHs and the associated cancer risk among global populations, encompassing both children and adults. Web of Science (WoS), Cochrane Library, PubMed, ProQuest, Scopus, and Google Scholar, were searched following the PRISMA guidelines, until December 31, 2023. Quality assessment of the selected studies was performed using the Newcastle-Ottawa Scale. The increased lifetime cancer risk (ILCR) attributed to PAH exposure through ingestion and dermal absorption was thoroughly examined across diverse age groups. After extensive searching, screening, and eligibility, 30 articles were included in this review, which was conducted in different parts of the world, including Nigeria (n = 11), China (n = 7), India (n = 4), Iran (n = 3), South Africa (n = 2), Italy (n = 1), Colombia (n = 1), and Iraq (n = 1). Our analysis underscores Nigeria's alarming prevalence of PAH contamination in its rivers, groundwaters, and seawater. Remarkably, the highest cancer risk was identified among children and adults, notably in proximity to the Atlas Cove jetty (seawater) and various Nigerian rivers. This elevated risk is primarily attributed to the combined effects of ingestion and dermal absorption. Furthermore, our findings emphasize the prominent role of combustion-derived and pyrogenic sources of PAH in the examined aquatic ecosystems. This study unequivocally establishes that PAH-contaminated water sources significantly amplify the risk of cancer among both children and adults. The extent of risk variation is influenced by the specific water source, duration of exposure, and age group. Consequently, proactive identification of contaminated water sources and their pollution origins, coupled with targeted educational campaigns, holds promise for reducing the global burden of PAH-related cancer.

13.
Turk Neurosurg ; 34(4): 573-577, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38874234

RESUMO

AIM: To describe the time between external ventricular drain (EVD) implantation and mobilization in neurosurgery intensive care unit (ICU) patients with EVDs. Due to increased intracranial pressure, neurosurgery patients with external ventricular drain (EVD) who are admitted to the ICU frequently remain at rest, resulting in prolonged ICU and hospital length of stay (LOS), mechanical ventilator (MV) duration, and other adverse effects. MATERIAL AND METHODS: A retrospective descriptive study was conducted on 131 neurosurgery patients admitted to the ICU with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) who underwent EVD. Time of mobilization, level of mobilization, ICU and hospital LOS, MV duration, and other factors were evaluated for patients who met the inclusion criteria. RESULTS: Of the 131 patients, 67 survived, and 61 began to mobilize in varying degrees of dangling (26.22%), standing (44.26%), and walking (29.5%). The mean number of days between EVD implantation and mobilization was 10.15. According to the findings, the mean ICU-LOS in patients was 14.56 days, the MV duration was 7.13 days, the time of ICU discharge from EVD removal was 7.08 days, and the hospital-LOS was 16.98 days. In addition, seven patients (10.44%) developed DVT, and three developed PE (4.47%). CONCLUSION: Prolonged immobility in patients with EVD is associated with negative outcomes such as PE and DVT, as well as an increase in MV duration, ICU-LOS, and hospital-LOS. Therefore, designing an appropriate and standard mobilization protocol and training nursing staff to assist patients in safely mobilizing can significantly reduce the complications above, reduce postoperative care, and empower patients.


Assuntos
Drenagem , Unidades de Terapia Intensiva , Tempo de Internação , Hemorragia Subaracnóidea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Drenagem/métodos , Tempo de Internação/estatística & dados numéricos , Idoso , Hemorragia Subaracnóidea/cirurgia , Adulto , Hemorragia Cerebral/cirurgia , Procedimentos Neurocirúrgicos/métodos , Deambulação Precoce , Fatores de Tempo , Respiração Artificial
14.
Phytomedicine ; 119: 154964, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37544212

RESUMO

BACKGROUND: Nutraceuticals have been important for more than two decades for their safety, efficacy, and outstanding effects. Diabetes is a major metabolic syndrome, which may be improved using nutritional pharmaceuticals. Some microalgae species, such as spirulina, stand out by providing biomass with exceptional nutritional properties. Spirulina has a wide range of pharmacological effects, mostly related to phycocyanin. Phycocyanin is a protein compound with antidiabetic properties, known as a nutraceutical. OBJECTIVE: This review delves into phycocyanin applications in diabetes and its complications and ascertains the mechanisms involved. METHODS: Scopus, PubMed, Cochrane Library, Web of Science, and ProQuest databases were systematically reviewed (up to April 30, 2023), in which only animal and cellular studies were found. RESULTS: According to animal studies, the administration of phycocyanin affected biochemical parameters (primary outcome) related to diabetes. These results showed an increase in fasting insulin serum and a decrease in fasting blood glucose, glycosylated serum protein, and glycosylated hemoglobin. In cellular studies, though, phycocyanin prevented methylglyoxal and human islet amyloid polypeptide-induced dysfunction in ß-cells and induced apoptosis through different molecular pathways (secondary outcome), including activation of Nrf2, PI3K/Akt, and suppression of JNK and p38. Also, phycocyanin exerted its antidiabetic effect by affecting the pathways regulating hepatic glucose metabolism. CONCLUSIONS: Thus, based on the available information and literature, targeting these pathways by phycocyanin may unleash an array of benefits, including positive outcomes of the antidiabetic effects of phycocyanin as a nutraceutical. OTHER: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) at the National Institute of Health. The registration number is CRD42022307522.


Assuntos
Células Secretoras de Insulina , Spirulina , Animais , Humanos , Ficocianina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Revisões Sistemáticas como Assunto , Hipoglicemiantes/farmacologia , Spirulina/química
15.
Pathol Res Pract ; 244: 154387, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36893710

RESUMO

Colorectal Neoplasia Differentially Expressed (CRNDE) is an lncRNA with crucial roles in cancer development. It is located on chromosome 16 on the opposite strand to the adjacent IRX5 gene, implying the presence of a shared bidirectional promoter for these two genes. Expression of CRNDE has been assessed in a diverse array of hematological malignancies and solid tumors, representing its potential as a therapeutic target in these conditions. This lncRNA has a regulatory effect on activity of several pathways and axes that are involved in the regulation of cell apoptosis, immune responses and tumorigenesis. The current review is an updated review about the role of CRNDE in the development of cancers.


Assuntos
MicroRNAs , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Apoptose/genética , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias/genética
16.
BMC Med Genomics ; 16(1): 328, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087279

RESUMO

BACKGROUND: In recent years, drug screening has been one of the most significant challenges in the field of personalized medicine, particularly in cancer treatment. However, several new platforms have been introduced to address this issue, providing reliable solutions for personalized drug validation and safety testing. In this study, we developed a personalized drug combination protocol as the primary input to such platforms. METHODS: To achieve this, we utilized data from whole-genome expression profiles of 6173 breast cancer patients, 312 healthy individuals, and 691 drugs. Our approach involved developing an individual pattern of perturbed gene expression (IPPGE) for each patient, which was used as the basis for drug selection. An algorithm was designed to extract personalized drug combinations by comparing the IPPGE and drug signatures. Additionally, we employed the concept of drug repurposing, searching for new benefits of existing drugs that may regulate the desired genes. RESULTS: Our study revealed that drug combinations obtained from both specialized and non-specialized cancer medicines were more effective than those extracted from only specialized medicines. Furthermore, we observed that the individual pattern of perturbed gene expression (IPPGE) was unique to each patient, akin to a fingerprint. CONCLUSIONS: The personalized drug combination protocol developed in this study offers a methodological interface between drug repurposing and combination drug therapy in cancer treatment. This protocol enables personalized drug combinations to be extracted from hundreds of drugs and thousands of drug combinations, potentially offering more effective treatment options for cancer patients.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Biologia Computacional , Quimioterapia Combinada , Neoplasias/tratamento farmacológico , Neoplasias/genética , Combinação de Medicamentos
17.
Comput Biol Med ; 161: 106997, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37216774

RESUMO

BACKGROUND AND AIMS: Acute ST-Segment Myocardial infarction (STEMI) is a common cardiovascular issue with a considerable burden of the disease. The underlying genetic basis and non-invasive markers were not well-established. METHODS: Here, we implemented a systematic literature review and meta-analyses integration methods on 217 STEMI patients and 72 normal individuals to prioritize and detect the STEMI-related non-invasive markers. Five high-scored genes were experimentally assessed on 10 STEMI patients and 9 healthy controls. Finally, the presence of co-expressed nodes of top-score genes was explored. RESULTS: The differential expression of ARGL, CLEC4E, and EIF3D were significant for Iranian patients. The ROC curve for gene CLEC4E revealed an AUC (95% CI) of 0.786 (0.686-0.886) in the prediction of STEMI. The Cox-PH model was fitted to stratify high/low risk heart failure progression (CI-index = 0.83, Likelihood-Ratio-Test = 3e-10). The SI00AI2 was a common biomarker between STEMI and NSTEMI patients. CONCLUSIONS: In conclusion, the high-scored genes and prognostic model could be applicable for Iranian patients.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Irã (Geográfico) , Infarto do Miocárdio/genética , Infarto do Miocárdio/diagnóstico , Biomarcadores , Fatores de Risco , Fator de Iniciação 3 em Eucariotos
18.
Heliyon ; 9(12): e22874, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125536

RESUMO

Background: The WASF3 gene has been linked to promoting metastasis in breast cancer (BC) cells, and low expression reduces invasion potential. Circular RNAs (circRNAs) function as microRNA (miRNA) modulators and are involved in cancer progression, but the relationship between these factors remains unclear. Methods: This study used bioinformatics methods and a computational approach to investigate the role of circRNAs and miRNAs in the context of WASF3 overexpression. Differentially expressed mRNAs, circRNAs, and miRNAs were identified using Gene Expression Omnibus (GEO) datasets. A competing endogenous RNA (ceRNA) network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Functional and pathway enrichment analyses were predicted using a circRNA-miRNA-mRNA network. Results: RNA expression patterns were significantly different between normal and tumor samples. A total of 190 circRNAs, 76 miRNAs, and 678 mRNAs were differentially expressed. The analysis of the circRNA-miRNA-mRNA regulatory network revealed interactions between hsa-circ-0100153, hsa-miR-31, hsa-miR-767-3p, and hsa-miR-935 with WASF3 in cancer. These interactions primarily function in DNA replication and the cell cycle. Conclusions: This study reveals a mechanism by which WASF3 overexpression affects the expression of circRNAs hsa-circ-0100153, promoting BC progression by sponging hsa-miR-31/hsa-miR-767-3p /hsa-miR-935. This mechanism may increase the invasive potential of cancers, in addition to other reported molecular mechanisms involving the WASF3 gene.

19.
Pathol Res Pract ; 243: 154346, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36746036

RESUMO

Recent decade has seen a tremendous progress in identification of the role of different long non-coding RNAs (lncRNAs) in human pathologies. ADAMTS9-AS2 is an example of lncRNAs with different roles in human disorders. It is mostly acknowledged as a tumor suppressor lncRNA in different types of cancers. However, it has been reported to be up-regulated in tongue squamous cell carcinoma, salivary adenoid cystic carcinoma and glioblastoma. Moreover, ADAMTS9-AS2 is possibly involved in the pathoetiology of pulpitis, acute ischemic stroke, type 2 diabetes and its complications. This lncRNA sponges miR-196b-5p, miR-223-3p, miR-130a-5p, miR-600, miR-223-3p, miR-27a-3p, miR-32, miR-143-3p, miR-143-3p and miR-182-5p in order to regulate downstream mRNAs. This review aims at summarization of the role of ADAMTS9-AS2 in different disorders with a particular focus on its diagnostic and prognostic values.


Assuntos
Carcinoma de Células Escamosas , Diabetes Mellitus Tipo 2 , AVC Isquêmico , MicroRNAs , RNA Longo não Codificante , Neoplasias da Língua , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células/genética , Proteína ADAMTS9/genética
20.
Pathol Res Pract ; 243: 154339, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36736143

RESUMO

Hippo pathway has been initially recognized as a regulatory mechanism for modulation of organ size in fruitfly. Subsequently, its involvement in the regulation of homeostasis and tumorigenesis has been identified. This pathway contains some tumor suppressor genes such as hippo (hpo) and warts (wts), as well as a number of oncogenic ones such as yorkie (yki). Recent studies have shown participation of Hippo pathway in the lung carcinogenesis. This pathway can affect lung cancer via different mechanisms. The interaction between some miRNAs and Hippo pathway is a possible mechanism for carcinogenic processes. Moreover, some other types of non-coding RNAs including PVT1, SFTA1P, NSCLCAT1 and circ_0067741 are implicated in this process. Besides, anti-cancer effects of gallic acid, icotinib hydrochloride, curcumin, ginsenoside Rg3, cryptotanshinone, nitidine chloride, cucurbitacin E, erlotinib, verteporfin, sophoridine, cisplatin and verteporfin in lung cancer are mediated through modulation of Hippo pathway. Here, we summarize the results of recent studies that investigated the role of Hippo signaling in the progression of lung cancer, the impact of non-coding RNAs on this pathway and the effects of anti-cancer agents on Hippo signaling in the context of lung cancer.


Assuntos
Proteínas de Drosophila , Neoplasias Pulmonares , Humanos , Via de Sinalização Hippo , Transdução de Sinais , Proteínas Serina-Treonina Quinases/genética , Verteporfina/farmacologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/farmacologia , Neoplasias Pulmonares/patologia
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