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1.
J Drug Target ; 32(5): 457-469, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38328920

RESUMO

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.


Assuntos
Nanopartículas , Humanos , Nanopartículas/toxicidade , Animais , Sistemas de Liberação de Medicamentos
2.
Cureus ; 16(1): e52353, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38361686

RESUMO

BACKGROUND: Anatomy is one of the most volatile subjects and needs the learner to understand and retain a lot of information and terms. It is thus very important to continuously upgrade the methodology from the traditional didactive to interactive teaching to make the student an active learner and engage him in the learning process to categorize and analyze anatomical facts and knowledge. AIMS AND OBJECTIVES: The study was done to compare the learning outcomes and perception of medical students towards didactic lectures and interactive quiz-based lectures in anatomy. METHODOLOGY: The study was conducted amongst the 200 Year 1 medical undergraduate students enrolled in the Department of Anatomy at Dr. Ram Manohar Lohia Institute of Medical Sciences, located in Lucknow, India. The 200 students comprised 120 males (60%) and 80 females (40%). The mean age of male students was 19.67 years and of females was 19.52 years. The students were divided into two groups of hundred students each by a method of convenience sampling. Students of group I were taught by an interactive quiz-based lecture and group II by a traditional didactic lecture. A pre- and post-test were conducted for both groups and feedback for both methods was taken by using a pre-validated feedback form based on a 5-point Likert scale. RESULTS: On statistical analysis, it was found that in the post-test the performance of group I taught by the interactive quiz-based study was better as compared to group II taught by traditional didactive teaching, but was not statistically significant (p=0.233, p>0.05). The feedback from students revealed that 45.9% of them strongly agreed and 44.9% agreed with the fact that quiz-based lectures are better than routine lectures. CONCLUSIONS: Results of the present study clearly indicate that the introduction of quiz-based anatomy teaching for undergraduate medical students was well received and appeared to improve their learning outcomes in the form of increased attention and participation during class and would lead to better retention of the topics taught during interactive lectures. To the best of our knowledge, no previous study has been done to document the efficacy of quiz-based teaching for the subject of anatomy.

3.
Pharm Dev Technol ; 29(1): 25-39, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38014878

RESUMO

BACKGROUND: Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. MAIN PART: Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. CONCLUSION: With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality.


Assuntos
Artrite , Sistemas de Liberação de Medicamentos , Humanos , Artrite/tratamento farmacológico , Géis
4.
South Asian J Cancer ; 12(3): 245-249, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38047044

RESUMO

Lakhan KasyapIntroduction Gallbladder cancer (GBC) is the 20th most common cancer in India with a crude incidence rate of 2.3 per 100,000 persons. Of note, it is relatively common in states which fall in the Gangetic plains. Patients often present in the advanced stage and have an unfavorable prognosis. Materials and Methods From January to June 2021, 170 treatment-naive GBC (adenocarcinoma) patients who were registered at a tertiary care cancer center in North India, were included. Data were extracted from electronic medical records and was analyzed with SPSS. Results Median age was 56 years (range 32-77 years) and 65.5% ( n = 112) were female. Incidental GBC was found in 20% patient ( n = 34). Majority of patients (79.4%, n = 135) had preserved performance status. Advanced GBC was present in 85.8% ( n = 146) patients (locally advanced = 37.0% and metastatic = 48.8%). Biliary drainage procedure was performed in 24% of patients (68% of patients with obstructive jaundice). More than half of patients (53.5%) were lost to follow-up without any treatment. There were 33 patients (19.4%) who underwent surgery and 20 of them received neoadjuvant chemotherapy. Adjuvant chemotherapy and adjuvant radiotherapy were received by 13 and 2 patients, respectively. Palliative chemotherapy was administered to 46 patients. The most common chemotherapy regimen was gemcitabine-cisplatin. At a median follow-up of 1.7 months (95% confidence interval, 1-2.4 months), 42 patients (24%) progressed and 24 patients (14%) died, with 6 months estimated progression-free survival and overall survival being 60.2 and 79%, respectively. Conclusion GBC is an aggressive and lethal malignancy predominantly affecting females in the fifth decade with dismal outcomes. Improved access to health care, an aggressive approach in operable cases, and optimization of systemic and adjuvant therapy are the need of the hour.

5.
Sci Rep ; 13(1): 21643, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38062163

RESUMO

Breast cancer is a highly aggressive type of cancer and has several subtypes, including triple-negative breast cancer (TNBC), which accounts for 25% of morbidity related to breast cancer. miRNAs are small non-coding RNA molecules that regulate 60% of human genes. Dysregulated expression of miRNA in liquid biopsy of TNBC patients has the potential as a minimally invasive diagnostic biomarker. The Association of miRNA with TNBC was evaluated using in-silico analysis. Highly enriched miRNAs were selected for functional analysis to evaluate the role of miRNA in the progression of TNBC. The qRT-PCR-based expression analysis of miRNA was performed in 190 serum samples (139 TNBC and 51 healthy). Revealed the elevated expression of miRNA-155 and miRNA-21 in TNBC compared to control samples (P < 0.0001), while miRNA-205 was significantly downregulated in TNBC (P < 0.0001). The combined diagnostic value of the miRNA-205, miRNA-155 and miRNA-21 in cohort-I, cohort-II, and cohort-III was AUC of 96.1% (P < 0.0001), 94.9% (P < 0.0001), and 97.1% (P < 0.0001), respectively. Our study revealed that dysregulated expression of miRNA could be used as an independent indicator for discriminating TNBC from healthy patients. In addition, the combined predictive value of miRNA-205 + miRNA - 155 + miRNA-21 has higher AUC, sensitivity, and specificity in the diagnosis of TNBC in all three cohorts.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética
6.
Health Sci Rep ; 6(5): e1262, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37205935

RESUMO

Background and Aims: Alexithymia is a state in which one cannot comprehend and put their emotions or feelings into words. It is a disturbance that is common among general population as well as people with mental health disorders. Medical students are at higher risk of developing alexithymia due to the extensive nature of their course and clinical postings. The presence of alexithymia is negatively correlated with the self-efficacy of the students eventually affecting self-care and patient care in the future. The aim of this study is to find the prevalence of alexithymia among medical students in Nepal and know its associated factors. Methods: This cross-sectional study used convenient sampling for selecting responders and the TAS-20 tool for data collection. Data were analyzed by using SPSS 20. Frequency was calculated for all the variables. Prevalence with 95% confidence interval [CI] is reported and the χ 2 test is used to see the difference in alexithymia status among different categories of dichotomous independent variables. Results: Out of 386 students, 380 of them responded. The ratio of male and female was 1.8 with the mean age of 22.22 ± 1.77 years. The prevalence of alexithymia was found to be 22.89% (95% CI, 18.9-27.1). There was no statistically significant difference between the presence and absence of alexithymia among categories of sex, year of study, staying at hostel, involvement in extracurricular activities, involvement in daily exercise/yoga/outdoor sports, and smoking habit. Conclusion: The prevalence of alexithymia in our study was 22.89% with no association with known factors.

7.
Int J Biol Macromol ; 220: 743-753, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35987358

RESUMO

Cold shock proteins (CSPs) are an ancient and conserved family of proteins. They are renowned for their role in response to low-temperature stress in bacteria and nucleic acid binding activities. In prokaryotes, cold and non-cold inducible CSPs are involved in various cellular and metabolic processes such as growth and development, osmotic oxidation, starvation, stress tolerance, and host cell invasion. In prokaryotes, cold shock condition reduces cell transcription and translation efficiency. Eukaryotic cold shock domain (CSD) proteins are evolved form of prokaryotic CSPs where CSD is flanked by N- and C-terminal domains. Eukaryotic CSPs are multi-functional proteins. CSPs also act as nucleic acid chaperons by preventing the formation of secondary structures in mRNA at low temperatures. In human, CSD proteins play a crucial role in the progression of breast cancer, colon cancer, lung cancer, and Alzheimer's disease. A well-defined three-dimensional structure of intrinsically disordered regions of CSPs family members is still undetermined. In this article, intrinsic disorder regions of CSPs have been explored systematically to understand the pleiotropic role of the cold shock family of proteins.


Assuntos
Proteínas e Peptídeos de Choque Frio , Resposta ao Choque Frio , Proteínas Intrinsicamente Desordenadas , Proteínas de Bactérias/química , Proteínas e Peptídeos de Choque Frio/química , Temperatura Baixa , Humanos , Proteínas Intrinsicamente Desordenadas/química , Estrutura Secundária de Proteína , RNA Mensageiro/genética
8.
Biochimie ; 201: 75-78, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35839919

RESUMO

Several G-protein coupled receptors (GPCR) are upregulated in Alzheimer's Disease (AD), which ought to facilitate neurotransmission, and improve cognition. Yet, despite this upregulation, associated physiological effects are not observed in AD patients. This paradox solicits urgent attention to find a suitable justification for disturbed neurotransmission in AD. This article focuses on the role of Aß granules and their possible interaction with GPCRs that modulate neurotransmission and AD progression.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Cognição , Humanos , Receptores Acoplados a Proteínas G , Transmissão Sináptica
9.
Saudi J Anaesth ; 16(2): 194-199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431746

RESUMO

Background: Facial area is one of the most frequently injured area of the body, accounting for 23-97% of all facial fractures. Treatments under general anesthesia as those for maxillofacial fractures or infections is a highly complicated and a major challenging task in trismus associated patients. The main culprit in trismus is the increase muscle tone of masticatory muscles which are supplied via the mandibular nerve, blocking which could help increase the mouth opening thus, changing the whole of airway management. Material and Method: A prospective study was done on 50 patients of ASA grade I-II with unilateral mandibular fracture with trismus posted for maxillofacial surgery. Mandibular nerve block was given via extraoral approach with 5 ml of 0.5% bupivacaine using peripheral nerve stimulator to determine the difference in Pre block and Post block mouth opening and the VAS score at 2, 5, 10, 15, 20, 25, and 30 minutes. Results: The Interincisor distance measured Pre block was 1.20 ± 0.32 mm and was significantly increased after 5 mins onwards from the block (P < 0.005). The VAS score determined Pre block was 5.14 ± 1.37 which significantly decreased just 2 minutes after the application of block (P < 0.005). Conclusion: Mandibular nerve block decreases the pain and will aid in the decision making by an anesthetist regarding airway management as it helps in increasing the inter incisor distance significantly. Moreover, given the feasibility and effectiveness of the block it could be included in standard of care protocol for mandibular fracture patients.

10.
J Biomol Struct Dyn ; 40(2): 673-684, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-32900274

RESUMO

Computational approaches have been helpful in high throughput screening of drug libraries and designing ligands against receptors. Alzheimer's disease is a complex neurological disorder, which causes dementia. In this disease neurons are damaged due to formation of Amyloid-beta plaques and neurofibrillary tangles, which along with some other factors contributes to disease development and progression. The objective of this study was to predict tertiary structures of five G-protein coulped neurotransmitter receptors; CHRM5, CYSLTR2, DRD5, GALR1 and HTR2C, that are upregulated in Alzheimer's disease, and to screen potential inhibitors for against these receptors. In this study, Comparative modelling, molecular docking, MMGBSA analysis, ADMET screening and molecular dynamics simulation were performed. Tertiary structures of the five GPCRs were predicted and further subjected to molecular docking against natural compounds. Pharmacokinetic studies of natural compounds were also conducted for assessing drug-likeness properties. Molecular dynamics simulations were performed to investigate the structural stability and binding affinities of each complex. Finally, the results suggested that ZINC04098704, ZINC31170017, ZINC05998597, ZINC67911229, and ZINC67910690 had better binding affinity with CHRM5, CYSLTR2, DRD5, GALR1, and HTR2C (5-HT2C) proteins, respectively.Communicated by Ramaswamy H. Sarma.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Humanos , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas G
11.
Curr Mol Pharmacol ; 15(3): 502-516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34036925

RESUMO

Post-traumatic stress disorder (PTSD), previously known as battle fatigue syndrome or shell shock, is a severe mental disturbance condition that is normally triggered by the experience of some frightening/scary events or trauma where a person undergoes some serious physical or mental harm or threatened. PTSD is a long-life effect of the continuous occurrence of traumatic conditions, leading to the production of feelings of helplessness, intense fear, and horror in the person. There are various examples of events that can cause PTSD, such as physical, mental, or sexual assault at home or working place by others, unexpected death of a loved one, an accidental event, war, or some kind of natural disaster. Treatment of PTSD includes the removal or reduction of these emotional feelings or symptoms with the aim to improve the daily life functioning of a person. Problems which are needed to be considered in case of PTSD like ongoing trauma, abusive or bad relationships. Various drugs which are used for the treatment of PTSD include selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluvoxamine, fluoxetine, etc.); tricyclic antidepressants (amitriptyline and isocarboxazid); mood stabilizers (Divalproex and lamotrigine); atypical antipsychotics (aripiprazole and quetiapine), etc. In this review, we have covered the different risk factors, case studies related to various treatment options with different age group of peoples with PTSD and their effects on them. We have also covered the symptoms and associated disorders which can play a key role in the development of PTSD.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Humanos , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico
12.
J Biomol Struct Dyn ; 40(21): 10887-10898, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34278961

RESUMO

Neurodegenerative disorders are illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Withania somnifera (Ashwagandha) in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of W. somnifera (WS) as potential inhibitors for the treatment of neurodegenerative diseases (ND). To fulfill this objective, Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 77 active components in WS, 175 predicted neurodegenerative targets of WS, and 8085 ND-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to ND. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer's disease pathways. Molecular docking results found that Anahygrine, Cuscohygrine, Isopelletierine, and Nicotine showed the best binding affinities -5.55, -4.73, -4.04, and -4.11 Kcal/mol. Further, MDS results suggested that Isopelletierine and Nicotine could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer's disease.Communicated by Ramaswamy H. Sarma.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Withania , Humanos , Withania/química , Doença de Alzheimer/tratamento farmacológico , Simulação de Acoplamento Molecular , Nicotina , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Extratos Vegetais/farmacologia
13.
Sci Rep ; 11(1): 17626, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475453

RESUMO

Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.


Assuntos
Biologia Computacional/métodos , Vacinas/imunologia , Vacinologia/métodos , Vacinas Bacterianas/imunologia , Doença de Chagas/imunologia , Doença de Chagas/prevenção & controle , Cólera/imunologia , Cólera/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Vibrio cholerae/imunologia
14.
Heliyon ; 6(11): e05546, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33294689

RESUMO

Alzheimer's disease is a progressive neurodegenerative disorder. In this disease neurodegeneration occurs due to deposition of aggregated amyloid-beta plaques and neurofibrillary tangles (hyperphosphorylated tau proteins). Present study focuses on interaction of different phytochemicals with presenilin stabilization factor like protein (PSFL). PSFL protein is known to stabilize Presenilin, which is mainly involved in intramembrane hydrolysis of selected type- I membrane proteins, including amyloid-beta precursor protein, and produces amyloid-beta protein. Amyloid-beta are small peptides comprising of 36-43 amino acids, which play a significant role in senile plaques formation in the brains of Alzheimer patients. Virtual screening and docking of phytochemicals with PSFL protein was done to find the potential inhibitor. Based on binding affinity, docked energy and molecular dynamics simulations, three phytochemicals namely Saponin, Casuarictin, and Enoxolone, were identified as potential inhibitors for the target protein.

15.
Ther Deliv ; 11(2): 125-137, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31937205

RESUMO

Niosomes, liposomes and proniosomes are the most abundantly used vesicular systems for the transdermal delivery of drugs. Proniosomes are nonhydrated niosomes, which, upon hydration, form niosomes. Various researches have proved the advantages of proniosomes over the other conventional dosage forms currently available in the market. Proniosomes overcome physical stability problems involved with other vesicular systems such as leaking, fusion and aggregation. The stability and shelf life of proniosomes especially have been found to be much better and prolonged in comparison to other vesicular systems such as liposomes. The present review has been written in an effort to bring yet another viewpoint from a different angle and curated to compile the latest updates in this highly attractive delivery system from today's research point.


Assuntos
Portadores de Fármacos , Lipossomos , Administração Cutânea , Sistemas de Liberação de Medicamentos
16.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180040

RESUMO

Human Y-box binding protein-1 (YBX1) is a member of highly conserved cold-shock domain protein family, which is involved in transcriptional as well as translational regulation of many genes. Nuclear localization of YBX1 has been observed in various cancer types and it's overexpression has been linked to adverse clinical outcome and poor therapy response, but no diagnostic or therapeutic correlation has been established so far. This study aimed to identify differentially expressed novel genes among the interactors of YBX1 in different cancer types. Analysis of RNA-Seq data for colorectal, lung, prostate and stomach adenocarcinoma identified 39 unique genes, which are differentially expressed in the four adenocarcinoma types. Gene-enrichment analysis for the differentially expressed genes from individual adenocarcinoma with focus on unique genes resulted in a total of 57 gene sets specific to each adenocarcinoma. Gene ontology for commonly expressed genes suggested the pathways and possible mechanisms through which they affect each adenocarcinoma type considered in the study. Gene regulatory network constructed for the common genes and network topology was analyzed for the central nodes. Here 12 genes were found to play important roles in the network formation; among them, two genes FOXM1 and TOP2A were found to be in central network formation, which makes them a common target for therapeutics. Furthermore, five common differentially expressed genes in all adenocarcinomas were also identified.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias da Próstata/genética , Neoplasias Gástricas/genética , Proteína 1 de Ligação a Y-Box/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Biologia Computacional/métodos , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Feminino , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Anotação de Sequência Molecular , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligação Proteica , Mapeamento de Interação de Proteínas , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteína 1 de Ligação a Y-Box/metabolismo
17.
Acta Orthop Belg ; 85(1): 21-34, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31023196

RESUMO

Landmine blast injuries are high velocity shattering injuries that produce ghastly and gory wounds, presenting a dilemma to the treating surgeon, especially when the literature on this subject is limited. The aim of the present study is to enlist various surgical procedures that can be explored to treat such complex injuries. 60 cases having varied degrees of involvement of the lower limb from mine blasts were managed. Surgical treatment was tailored to the individual requirement depending on the extent and severity of injury. Serial surgical wound debridement was an integral part of all these procedures. Limb length preservation was possible in 70% cases. A combination of surgical approaches and procedures from fixation to different types of amputations can be employed for treating mine blast injuries to maximise residual limb function.


Assuntos
Amputação Cirúrgica/métodos , Traumatismos por Explosões/cirurgia , Desbridamento , Extremidade Inferior/cirurgia , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retalhos Cirúrgicos , Adulto Jovem
18.
Mol Ther Nucleic Acids ; 12: 490-503, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30195786

RESUMO

Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a diverse genetic makeup and differential miRNA profile. Aiming to identify deregulated miRNAs in MB, the miRNA expression profile of human MB samples was compared to that of normal cerebellar tissues. As a result, 8 upregulated and 64 downregulated miRNAs were identified in MB samples. Although various algorithms have been developed to predict the interaction between miRNA-mRNA pairs, the complexity and fidelity of miRNA-mRNA remain a concern. Therefore, to identify the signatures of miRNA-mRNA interactions essential for MB pathogenesis, miRNA profiling, RNA sequencing, and ingenuity pathway analysis (IPA) were performed in the same primary human MB samples. Further, when miR-217 was inhibited, a significant upregulation of predicted target genes SIRT1, ROBO1, FOXO3, and SMAD7 in HDMB03 cells was observed, confirming the validity of our approach. Functional analysis revealed that the inhibition of miR-217 in HDMB03 cells suppresses colony formation, migration, invasion, promoted apoptosis, and arrested cell population in S phase, indicating that manipulation of miR-217 may have a therapeutic potential for MB patients. Therefore, our study provides an essential platform for future investigations of specific miRNAs responsible for MB pathogenesis.

19.
Microbiol Res ; 214: 37-46, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30031480

RESUMO

The orphan histidine kinase (HK) from Streptomyces peucetius ATCC 27952 (ohkAsp) was found to be implicated in the regulation of doxorubicin (DOX)/daunorubicin (DNR) biosynthesis, self-defense and developmental attributes. OhkAsp is a homolog of OhkA from Streptomyces coelicolor and Streptomyces avermitilis (with 73 and 75% identity). As in its homologs, S. peucetius mutant with deletion of ohkAsp was found to enhance metabolite biosynthesis and impaired the morphological differentiation. But, unlike its homologs from Streptomyces coelicolor and Streptomyces avermitilis, differential enhancement in level of secondary metabolite production was found in overexpression mutants apart from deletion mutant. The deflection in characteristics of OhkA in its homologue from S. peucetius ATCC 27952, and its imminent implications was monitered by making various mutants with differential expression level of ohkAsp. The variations were observed in the morphology of mutants, transcriptional level of effectors and regulators of DOX/DNR biosynthesis pathway, DOX/DNR precursor pool and biomass accumulation. Based on comparisons of domain arrangements among its homologs, Low Complexity Region (LCR) present on the OhkAsp was the only domain that stood out. Further, the LCR on OhkAsp was found to be overlapping with a putative receiver domain responsible for interaction with response regulator. The imminent implications of differential expression level of ohkAsp on: regulation and biosynthesis of DOX/DNR, morphological differentiation, DOX/DNR precursor pool and biomass accumulation were explored in this study.


Assuntos
Antibióticos Antineoplásicos/biossíntese , Daunorrubicina/biossíntese , Doxorrubicina/biossíntese , Histidina Quinase/metabolismo , Streptomyces/enzimologia , Streptomyces/metabolismo , Análise Mutacional de DNA , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Genótipo , Histidina Quinase/genética , Fenótipo , Streptomyces/citologia
20.
J Genomics ; 6: 103-112, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29973960

RESUMO

Y-Box Binding protein 1 (YBX-1) is known to be involved in various types of cancers. It's interactors also play major role in various cellular functions. Present work aimed to study the expression profile of the YBX-1 interactors during lung adenocarcinoma (LUAD). The differential expression analysis involved 57 genes from 95 lung adenocarcinoma samples, construction of gene network and topology analysis. A Total of 43 genes were found to be differentially expressed from which 17 genes were found to be down regulated and 26 genes were up-regulated. We observed that Polyadenylate-binding protein 1 (PABPC1), a protein involved in YBX1 translation, is highly correlated with YBX1. The interaction network analysis for a differentially expressed non-coding RNA Growth Arrest Specific 5 (GAS5) suggests that two proteins namely, Growth Arrest Specific 2 (GAS2) and Peripheral myelin protein 22 (PMP22) are potentially involved in LUAD progression. The network analysis and differential expression suggests that Collagen type 1 alpha 2 (COL1A2) can be potential biomarker and target for LUAD.

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