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Haberlea rhodopensis, a resurrection species, is the only plant known to be able to survive multiple extreme environments, including desiccation, freezing temperatures, and long-term darkness. However, the molecular mechanisms underlying tolerance to these stresses are poorly studied. Here, we present a high-quality genome of Haberlea and found that ~ 23.55% of the 44,306 genes are orphan. Comparative genomics analysis identified 89 significantly expanded gene families, of which 25 were specific to Haberlea. Moreover, we demonstrated that Haberlea preserves its resurrection potential even in prolonged complete darkness. Transcriptome profiling of plants subjected to desiccation, darkness, and low temperatures revealed both common and specific footprints of these stresses, and their combinations. For example, PROTEIN PHOSPHATASE 2C (PP2C) genes were substantially induced in all stress combinations, while PHYTOCHROME INTERACTING FACTOR 1 (PIF1) and GROWTH RESPONSE FACTOR 4 (GRF4) were induced only in darkness. Additionally, 733 genes with unknown functions and three genes encoding transcription factors specific to Haberlea were specifically induced/repressed upon combination of stresses, rendering them attractive targets for future functional studies. The study provides a comprehensive understanding of the genomic architecture and reports details of the mechanisms of multi-stress tolerance of this resurrection species that will aid in developing strategies that allow crops to survive extreme and multiple abiotic stresses.
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Temperatura Baixa , Genômica , Produtos Agrícolas , Ambientes Extremos , Perfilação da Expressão GênicaRESUMO
Cloning and expression of a gene in the desired host is required for optimum production in recombinant strains. The present research is the first attempt to optimize the physiological conditions for the transformation of Pseudomonas aeruginosa SDK-6 with pJN105. Different factors, such as inoculum size, incubation period, heat shock temperature, and heat shock time were optimized using one factor at a time (OFAT) followed by the selection of transformants using gentamicin resistance marker. The maximum number of transformants (2.002 ± 0.077 × 105 cfu/ µg of plasmid DNA) were reported with 0.5% (v/v) inoculum, an incubation period of 3 h, and heat shock treatment at 50 °C for 1 min. An overall 12-fold increase in transformation efficiency was observed. The presence of a 6055 bp band on agarose gel confirmed the transformation of Pseudomonas aeruginosa with the vector pJN105.
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Clonagem Molecular , Vetores Genéticos , Plasmídeos , Pseudomonas aeruginosa , Transformação Bacteriana , Pseudomonas aeruginosa/genética , Plasmídeos/genética , Vetores Genéticos/genética , Cloreto de CálcioRESUMO
Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM.
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Antibacterianos , Anti-Inflamatórios , Mastite Bovina , Plantas Medicinais , Animais , Bovinos , Mastite Bovina/microbiologia , Mastite Bovina/tratamento farmacológico , Mastite Bovina/prevenção & controle , Plantas Medicinais/química , Anti-Inflamatórios/farmacologia , Feminino , Antibacterianos/farmacologia , Humanos , Leite , Dieta/veterinária , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: Migraine prevalence and levels of calcitonin gene-related peptide (CGRP), a peptide involved in migraine pathophysiology, differ between men and women, and appear to be affected by changes in sex hormones. The present study investigated the sex-specific responses to CGRP in human isolated arteries. METHODS: CGRP-induced relaxation of 62 (28 men and 34 women) human isolated middle meningeal arteries (HMMA) and 139 (69 men and 70 women) human isolated coronary arteries (HCA) was compared between men and women in groups <50 years and ≥50 years of age as a proxy for pre- and postmenopausal status in women, as well as matched-age groups for men. RESULTS: In HCA, no differences were observed between male and female tissue, or between the different age groups. However, in HMMA, the maximum response was significantly smaller and CGRP was less potent in females <50 compared with males <50 years of age. No differences were observed between the older age groups. CONCLUSIONS: Sex differences were observed for CGRP-induced relaxation of HMMA, but not HCA. These differences could arise from differential receptor expression in the vascular beds combined with the effect of sex hormones on CGRP and subsequent receptor desensitization.
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Peptídeo Relacionado com Gene de Calcitonina , Vasos Coronários , Artérias Meníngeas , Transtornos de Enxaqueca , Caracteres Sexuais , Vasodilatação , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/metabolismo , Artérias Meníngeas/efeitos dos fármacos , Artérias Meníngeas/fisiologia , Vasodilatação/fisiologia , Vasodilatação/efeitos dos fármacos , Adulto , Vasos Coronários/efeitos dos fármacos , IdosoRESUMO
CRISPR-based (Clustered regularly interspaced short palindromic repeats-based) technologies have revolutionized molecular biology and diagnostics, offering unprecedented precision and versatility. However, challenges remain, such as high costs, demanding technical expertise, and limited quantification capabilities. To overcome these limitations, innovative microfluidic platforms are emerging as powerful tools for enhancing CRISPR diagnostics. This review explores the exciting intersection of CRISPR and microfluidics, highlighting their potential to revolutionize healthcare diagnostics. By integrating CRISPR's specificity with microfluidics' miniaturization and automation, researchers are developing more sensitive and portable diagnostic tools for a range of diseases. These microfluidic devices streamline sample processing, improve diagnostic performance, and enable point-of-care applications, allowing for rapid and accurate detection of pathogens, genetic disorders, and other health conditions. The review discusses various CRISPR/Cas systems, including Cas9, Cas12, and Cas13, and their integration with microfluidic platforms. It also examines the advantages and limitations of these systems, highlighting their potential for detecting DNA and RNA biomarkers. The review also explores the key challenges in developing and implementing CRISPR-driven microfluidic diagnostics, such as ensuring robustness, minimizing cross-contamination, and achieving robust quantification. Finally, it highlights potential future directions for this rapidly evolving field, emphasizing the transformative potential of these technologies for personalized medicine and global health.
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Sistemas CRISPR-Cas , Microfluídica , Sistemas CRISPR-Cas/genética , Humanos , Microfluídica/métodos , Patologia Molecular/métodos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Técnicas de Diagnóstico Molecular/métodos , Edição de Genes/métodos , Dispositivos Lab-On-A-ChipRESUMO
We recently encountered several cases of tetralogy of Fallot with an abnormally oriented S-shaped ascending aorta. In this retrospective study, we sought to clarify morphology of this unusual under-recognized variant. Databases were reviewed to identify all patients with tetralogy of Fallot having an S-shaped ascending aorta. Computed tomographic angiography was used for the assessment of cardiac morphology. Out of the 21 patients, 18 (86%) had a right aortic arch, 2 (9%) had a left aortic arch, and the remaining patient (5%) had a double aortic arch. Patients with a right aortic arch, compared to age and sex-matched patients with a right aortic arch but normally oriented ascending aorta, had lesser aortic override (29.3 ± 14% vs 54.8 ± 13.2%; p = 0.0001) and a wider ascending aorta (25.2 ± 6.9 vs 18.0 ± 3.2 mm; p = 0.0003). The S-shaped ascending aorta was located posteriorly, with a higher sterno-aortic distance (25.5 ± 7.7 vs 9.9 ± 4.5 mm; p = 0.0001). The ascending aorta among patients with tortuosity was longer (4.12 ± 1.7 vs 3.07 ± 0.82, p = 0.03) but with similar tortuosity index (1.22 ± 0.19 vs 1.15 ± 0.17, p = 0.23). Of the cases with right aortic arch and S-shaped ascending aorta, 16 (89%) had extrinsic compression of the right pulmonary artery (p = 0.0001), while 7 (39%) had crossed pulmonary arteries (p = 0.008), with no such findings among those with normally oriented ascending aorta. Tetralogy of Fallot with an S-shaped ascending aorta is a variant with lesser aortic override and a more posteriorly located ascending aorta. Compression of the right pulmonary artery and crossed pulmonary arteries is frequent in the presence of a right-sided aortic arch. These findings have important implications for optimal diagnosis and surgical repair.
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Ideally, the morphology of atrial appendages should solely be used to identify and differentiate patients with isomeric right and left atrial appendages. However, in clinical practice, the segregation is often indirectly based on the arrangement of thoraco-abdominal structures. The correlation between thoraco-abdominal arrangement and atrial appendages, however, is imperfect. In this study, we sought to clarify the cardiovascular malformations in patients with isomeric atrial appendages with an emphasis on atrial-thoracic-abdominal disharmony. A retrospective review of all patients who underwent cardiac CT angiography between January 2014 and June 2023 and identified to have isomeric atrial appendages was performed. Of the 366 cases (median age: 2 years [interquartile range: 11 months-7 years]), 247 (67.5%) patients had isomeric right atrial appendages while 119 (32.5%) patients had isomeric left atrial appendages. In 316 (86.3%) patients, the thoraco-abdominal arrangement was as per atrial appendage morphology while the remaining 50 (13.6%) patients had disharmonious patterns. Compared to isomeric left atrial appendages, the disharmonious pattern was more frequent with isomeric right atrial appendages (5.9% vs. 17.4%; p 0.003). Irrespective of the type of isomerism, disharmony was mostly confined to the level of the abdomen. Not all patients with isomeric atrial appendages have a harmonious thoraco-abdominal arrangement. The atrial-bronchial-abdominal disharmony is more frequent with isomeric right atrial appendages and is mostly present at the level of the abdomen. A detailed sequential segmental analysis with an independent description of each organ system is, therefore, essential for the complete evaluation of patients with isomeric atrial appendages.
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Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.
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PURPOSE: The complex anatomy of acetabular fracture needs a surgical approach that can achieve anatomical reduction with fewer complications for the fixation of these fractures. Current literature suggests that both Pararectus (PR) approach and Ilioinguinal (IL) approach can be used for the fixation of these fractures safely. However, superiority of the PR approach over the IL approach is not established. Hence, this meta-analysis aimed to compare the PR versus IL approach. METHODOLOGY: A literature search was performed on five databases Medline/PubMed, Scopus Embase, Cinhal, and Cochrane Library, from the inception to January 14, 2023. A qualitative and quantitative analysis was done for the five eligible studies from the literature search. Individual study characteristics data and outcomes were extracted, and Software version 5.4.1 of Review Manager was used for statistical analysis. RESULTS: Five articles, one Randomized trial (RCT), and four retrospective articles were included and analyzed in this meta-analysis. PR approach has a shorter surgical time [mean difference (MD) -48.4 with 95% CI -74.49, -22.30; p = 0.0003], less intraoperative blood loss (MD -123.22 with 95% CI -212.28, -34.15; p = 0.007), and smaller surgical incision (MD -9.87 with 95% CI -15.21, -4.52; p = 0.0003) than the IL approach. However, the meta-analysis failed to show a difference between the two surgical approaches concerning the quality of reduction, overall complications, nerve injury, vascular injury, heterotopic ossification, deep vein thrombosis, and pulmonary embolism. CONCLUSION: The PR approach has a shorter surgical duration, less blood loss, and a smaller surgical incision than the IL approach. However, both surgical approaches have equivocal results regarding fracture reduction quality, complication rates, and functional outcomes for acetabular fracture fixation. Hence, for acetabular fractures fixation, PR approach can be considered a safe and feasible alternative to the IL approach.
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Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Ferida Cirúrgica , Humanos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Estudos Retrospectivos , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Acetábulo/lesões , Fraturas do Quadril/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: The pararectus approach is a minimally invasive surgical approach for anterior acetabulum fracture, with an advantage of the medial window of the modified Stoppa approach (MSA). However, it is unclear whether the pararectus approach is superior to MSA. We aimed this systematic review and meta-analysis to compare the outcomes and complications of pararectus and MSA. METHODS: We performed a data search by conducting an electronic search across databases of PubMed, Embase, Scopus, Cinahl, CNKI, and Cochrane Library and included seven comparative studies for analysis. Statistical analysis was performed using the RevMan software 5.4.1. The risk of bias was evaluated using the Cochrane Collaboration's risk of bias tool for RCTs and the MINORS tool for non-RCTs. RESULTS: Two randomized control trials (RCTs), one prospective study, and four retrospective studies were included. Meta-analysis revealed a better Matta's reduction quality [OR 1.58, 95% CI 1.06, 2.37; p = 0.03] and radiological outcome [OR 2.18, 95% CI 1.03, 4.60; p = 0.04] in MSA than in pararectus approach. However, the pararectus approach has less intraoperative blood loss [MD - 9.79 (95% CI - 176.75, - 6.83; p = 0.03)] and a shorter hospital stay [MD - 2.61 (95% CI - 5.03, - .18; p = 0.04)] than MSA. Both approaches have failed to show a difference concerning overall complication rates [OR 0.66 (95% CI 0.28, 1.55; p = 0.34)], postoperative infection, DVT, duration of surgery [MD - 15.09 (95% CI - 35.38, 5.20; p = 0.15)], functional outcome, and incision length. CONCLUSION: The pararectus approach offers an advantage with lesser operative blood loss and shorter hospital stay, whilst MSA stands out with better reduction quality and radiological outcomes. Nevertheless, both approaches exhibit no difference in complication rates, duration of surgery, incision length, and functional outcome. Hence, the pararectus approach can be considered an alternative to MSA; however, the existing literature fails to demonstrate a distinct advantage over MSA.
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INTRODUCTION: Pelvic ring fractures, particularly those involving the posterior pelvis, pose significant challenges due to their inherent instability. The posterior pelvic ring is critical in providing structural support and stability to the pelvis. This study evaluates the functional outcomes and health-related Quality of life (HRQOL) of patients who underwent internal fixation for unstable pelvic fractures. Various factors influencing the outcomes are also investigated. MATERIAL AND METHODS: A single-center cross-sectional study was conducted on patients with unstable sacral fractures treated with posterior tension band plate or sacroiliac plating with or without symphyseal plating between 2016 and 2020. Patient demographics, injury mechanisms, associated injuries, surgical details, complications, and return-to-work data were collected. HRQOL was assessed using specific pelvic fracture instruments and general HRQOL questionnaires. Logistic regression analysis was performed to identify factors associated with lower SF-12 and SF-36 scores RESULTS: The study included 54 patients, predominantly males (55.6%), aged 18-70 years, with high-energy trauma mechanisms, such as road traffic accidents and occupational injuries. The majority of patients had lateral compression pelvic fractures. Overall, the functional outcomes were favorable, with excellent or good outcomes observed in 86.1% of cases. Patients with associated injuries, such as abdominal, chest, or head injuries, were likelier to have lower SF-12 physical component scores. Sexual satisfaction scores remained stable for most patients post-surgery. DISCUSSION: This study highlights the favorable functional outcomes and HRQOL for patients undergoing fixation for unstable pelvic ring fractures. Younger, working-age males were the most commonly affected demographic. Associated injuries significantly affected physical HRQOL scores. Despite high-energy trauma, patients generally reported satisfactory sexual function post-surgery.
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Fixação Interna de Fraturas , Fraturas Ósseas , Ossos Pélvicos , Qualidade de Vida , Humanos , Masculino , Estudos Transversais , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Pessoa de Meia-Idade , Feminino , Adulto , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/efeitos adversos , Fraturas Ósseas/cirurgia , Fraturas Ósseas/psicologia , Idoso , Adolescente , Adulto Jovem , Placas Ósseas , Resultado do Tratamento , Recuperação de Função FisiológicaRESUMO
Although several large-scale single-cell RNA sequencing (scRNAseq) studies addressing the root of Arabidopsis (Arabidopsis thaliana) have been published, there is still need for a de novo reference map for both root and especially above-ground cell types. As the plants' transcriptome substantially changes throughout the day, shaped by the circadian clock, we performed scRNAseq on both Arabidopsis root and above-ground tissues at defined times of the day. For the root scRNAseq analysis, we used tissue-specific reporter lines grown on plates and harvested at the end of the day (ED). In addition, we submitted above-ground tissues from plants grown on soil at ED and end of the night to scRNAseq, which allowed us to identify common cell types/markers between root and shoot and uncover transcriptome changes to above-ground tissues depending on the time of the day. The dataset was also exploited beyond the traditional scRNAseq analysis to investigate non-annotated and di-cistronic transcripts. We experimentally confirmed the predicted presence of some of these transcripts and also addressed the potential function of a previously unidentified marker gene for dividing cells. In summary, this work provides insights into the spatial control of gene expression from nearly 70,000 cells of Arabidopsis for below- and whole above-ground tissue at single-cell resolution at defined time points.
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Arabidopsis/química , Raízes de Plantas/química , Brotos de Planta/química , Transcriptoma , Ritmo Circadiano , Análise de Célula ÚnicaRESUMO
BACKGROUND: Dysphagia palliation in inoperable esophageal cancer continues to be a challenge. Self-expandable metal stents have been the mainstay of endoscopic palliation but have a significant risk of adverse events (AEs). Liquid nitrogen spray cryotherapy is an established modality that can be used with systemic therapy. This study reports the outcomes of cryotherapy, including dysphagia and quality of life (QoL), in patients receiving systemic therapy. METHODS: This was a prospective multicenter cohort study of adults with inoperable esophageal cancer who underwent cryotherapy. QoL and dysphagia scores before and after cryotherapy were compared. RESULTS: 55 patients received 175 cryotherapy procedures. After a mean of 3.2 cryotherapy sessions, mean QoL improved from 34.9âat baseline to 29.0âat last follow-up (Pâ<â0.001) and mean dysphagia improved from 1.9 to 1.3 (Pâ=â0.004). Patients receiving more intensive cryotherapy (≥â2 treatments within 3 weeks) showed a significantly greater improvement in dysphagia compared with those not receiving intensive therapy (1.2 vs. 0.2 points; Pâ=â0.003). Overall, 13 patients (23.6â%) received another intervention (1 botulinum toxin injection, 2 stent, 3 radiation, 7 dilation) for dysphagia palliation. Within the 30-day post-procedure period, there were three non-cryotherapy-related grade ≥â3 AEs (all deaths). The median overall survival was 16.4 months. CONCLUSION: In patients with inoperable esophageal cancer receiving concurrent systemic therapy, adding liquid nitrogen spray cryotherapy was safe and associated with improvement in dysphagia and QoL without causing reflux. More intensive treatment showed a greater improvement in dysphagia and should be considered as the preferred approach.
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Transtornos de Deglutição , Neoplasias Esofágicas , Adulto , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Qualidade de Vida , Estudos de Coortes , Estudos Prospectivos , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/terapia , Crioterapia/efeitos adversos , Stents/efeitos adversos , Nitrogênio , Cuidados Paliativos/métodosRESUMO
As far as health issues are concerned, cancer causes one out of every six deaths around the globe. As potent therapeutics are still awaited for the successful treatment of cancer, some unconventional treatments like radiotherapy, surgery, and chemotherapy and some advanced technologies like gene therapy, stem cell therapy, natural antioxidants, targeted therapy, photodynamic therapy, nanoparticles, and precision medicine are available to diagnose and treat cancer. In the present scenario, the prime focus is on developing efficient nanomedicines to treat cancer. Although stem cell therapy has the capability to target primary as well as metastatic cancer foci, it also has the ability to repair and regenerate injured tissues. However, nanoparticles are designed to have such novel therapeutic capabilities. Targeted therapy is also now available to arrest the growth and development of cancer cells without damaging healthy tissues. Another alternative approach in this direction is photodynamic therapy (PDT), which has more potential to treat cancer as it does minimal damage and does not limit other technologies, as in the case of chemotherapy and radiotherapy. The best possible way to treat cancer is by developing novel therapeutics through translational research. In the present scenario, an important event in modern oncology therapy is the shift from an organ-centric paradigm guiding therapy to complete molecular investigations. The lacunae in anticancer therapy may be addressed through the creation of contemporary and pertinent cancer therapeutic techniques. In the meantime, the growth of nanotechnology, material sciences, and biomedical sciences has revealed a wide range of contemporary therapies with intelligent features, adaptable functions, and modification potential. The development of numerous therapeutic techniques for the treatment of cancer is summarized in this article. Additionally, it can serve as a resource for oncology and immunology researchers.
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Nanopartículas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Transplante de Células-Tronco , Medicina de PrecisãoRESUMO
The past several decades have witnessed the emergence and re-emergence of many infectious viral agents, flaviviruses, influenza, filoviruses, alphaviruses, and coronaviruses since the advent of human deficiency virus (HIV). Some of them even become serious threats to public health and have raised major global health concerns. Several different medicinal compounds such as anti-viral, anti-malarial, and anti-inflammatory agents, are under investigation for the treatment of these viral diseases. These therapies are effective improving recovery rates and overall survival of patients but are unable to heal lung damage caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, there is a critical need to identify effective treatments to combat this unmet clinical need. Due to its antioxidant and immunomodulatory properties, stem cell therapy is considered a novel approach to regenerate damaged lungs and reduce inflammation. Stem cell therapy uses a heterogeneous subset of regenerative cells that can be harvested from various adult tissue types and is gaining popularity due to its prodigious regenerative potential as well as immunomodulatory and anti-inflammatory properties. These cells retain expression of cluster of differentiation markers (CD markers), interferon-stimulated gene (ISG), reduce expression of pro-inflammatory cytokines and, show a rapid proliferation rate, which makes them an attractive tool for cellular therapies and to treat various inflammatory and viral-induced injuries. By examining various clinical studies, this review demonstrates positive considerations for the implications of stem cell therapy and presents a necessary approach for treating virally induced infections in patients.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/terapia , Interferons , Pulmão , Transplante de Células-TroncoRESUMO
BACKGROUND: Paratuberculosis is a worldwide endemic infectious disease of ruminants that results in high economic losses. Public health concerns are also being raised with human Crohn's disease. Therefore, control is becoming priority for governments. Control is largely dependent on "Test and Cull" or "Test and Segregate" policy. Hence, it is critical to assure the infection before making the decision. Commercial kits are costly especially in view of resource limited areas. Present study analyzed the performance various in house DNA isolation methods and PCR master mix combinations to optimize a protocol for confirmation of paratuberculosis bacilli shedding in feces. METHODS AND RESULTS: Present study included five protocols of fecal DNA isolation (chemical, bio-chemical, physio-chemical and physical) and three reaction mixes (based on Qiagen, Genei and Thermo 2X master mixes) in nine different combinations using additives and tested their performance for IS900 PCR. Spiked fecal samples were used to select the best combination of DNA isolation method and PCR master mix (PRM). Selected combination was used to test reference (positive and negative) fecal samples and field samples. Findings revealed that combination physical method of DNA isolation and Genei based PRM (with additives; betaine DMSO and BSA) had lowest limit of detection. Sensitivity was 83% and specificity was 100% in comparison to fecal culture. High prevalence (23%) was reported for paratuberculosis on field samples. CONCLUSION: Optimized protocol has acceptable sensitivity and can easily be adopted in resource-limited laboratories. High prevalence of paratuberculosis needs immediate implementation of the control strategies.
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Doenças dos Bovinos , Mycobacterium avium subsp. paratuberculosis , Paratuberculose , Bovinos , Animais , Humanos , Paratuberculose/diagnóstico , Mycobacterium avium subsp. paratuberculosis/genética , Sensibilidade e Especificidade , Doenças dos Bovinos/diagnóstico , Reação em Cadeia da Polimerase/métodos , DNA , Fezes/química , DNA Bacteriano/genética , DNA Bacteriano/análiseRESUMO
Polyarteritis nodosa (PAN) is a medium-vessel vasculitis presenting with cutaneous and multisystem involvement with considerable morbidity. The necrotizing vasculitis in PAN typically involves renal, celiac, and mesenteric vascular beds. Coronary artery involvement is a characteristic feature of Kawasaki disease, another medium-vessel vasculitis; however, it has been rarely reported with PAN. Here, we present 2 cases with PAN involving coronaries mimicking Kawasaki disease. A 3.5-year-old boy with classical features of Kawasaki disease with giant coronary aneurysm refractory to IVIg, methylprednisolone, infliximab presented with persistent rise in inflammatory markers and gastrointestinal bleeding. Digital subtraction angiography (DSA) revealed celiac artery branches stenosis and beading suggestive of PAN. Another 2-year-old girl presented with persistent fever, abdominal pain, and distension. She had hypertension, hepatomegaly, and splenomegaly on examination. Echocardiography revealed multiple coronary aneurysms and DSA revealed numerous renal artery aneurysms. Coronary aneurysm although is a rare presentation of childhood PAN, and can mimic Kawasaki disease. Although both are medium-vessel vasculitis differentiation between these two entities is pivotal, as there are differences in treatment modalities, duration of immunomodulatory therapy, and the outcome. This manuscript describes the salient differences which can help differentiate PAN masquerading as Kawasaki disease at initial presentation.
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INTRODUCTION: Pulmonary arterial compliance, the dynamic component of pulmonary vasculature, remains inadequately studied in patients with left to right shunts. We sought to study the pulmonary arterial compliance in patients with left to right shunt lesions and its utility in clinical decision-making. MATERIALS AND METHODS: In this single-centre retrospective study, we reviewed cardiac catheterisation data of consecutive patients of left to right shunt lesions catheterised over one year. In addition to the various other parameters, pulmonary arterial compliance was calculated, as indexed pulmonary flow (Qpi) / (Heart rate × pulse pressure in the pulmonary artery). RC time was also calculated, as the product of pulmonary arterial compliance and pulmonary vascular resistance index. Patients were divided into "operable," "borderline," and "inoperable" based on the decision of the treating team, and the pulmonary arterial compliance values were evaluated in these groups to study if it can be utilised to refine the operability decision. RESULTS: 298 patients (Median age 16 years, 56% <18 years) with various acyanotic shunt lesions were included. Overall, the pulmonary arterial compliance varied with Qpi, pulmonary artery mean pressure, and pulmonary vascular resistance index, but did not vary with age, type of lesion, or transpulmonary gradients. The median pulmonary arterial compliance in patients with normal pulmonary artery pressure (Mean pulmonary artery pressure less than 20 mmHg) was 4.1 ml/mmHg/m2 (IQR 3.2). The median pulmonary arterial compliance for operable patients was 2.67 ml/mmHg/m2 (IQR 2.2). Median pulmonary arterial compliance was significantly lower in both inoperable (0.52 ml/mmHg/m2, IQR 0.34) and borderline (0.80 ml/mmHg/m2, IQR 0.36) groups when compared to operable patients (p < 0.001). A pulmonary arterial compliance value lower than 1.18 ml/mmHg/m2 identified inoperable patients with high sensitivity and specificity (95%, AUC 0.99). However, in borderline cases, assessment by this value did not agree with empirical clinical assessment.The median RC time for the entire study population was 0.47 S (IQR 0.30). RC time in operable patients was significantly lower than that in the inoperable patients (Median 0.40 IQR 0.23 in operable, 0.73 0.25 in inoperable patients (p < 0.001). CONCLUSIONS: Addition of pulmonary arterial compliance to the routine haemodynamic assessment of patients with shunt lesions may improve our understanding of the pulmonary circulation and may have clinical utility.
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Hipertensão Pulmonar , Artéria Pulmonar , Humanos , Adolescente , Circulação Pulmonar , Estudos Retrospectivos , Resistência VascularRESUMO
miRNA-146a, a single-stranded, non-coding RNA molecule, has emerged as a valuable diagnostic and prognostic biomarker for numerous pathological conditions. Its primary function lies in regulating inflammatory processes, haemopoiesis, allergic responses, and other key aspects of the innate immune system. Several studies have indicated that polymorphisms in miRNA-146a can influence the pathogenesis of various human diseases, including autoimmune disorders and cancer. One of the key mechanisms by which miRNA-146a exerts its effects is by controlling the expression of certain proteins involved in critical pathways. It can modulate the activity of interleukin-1 receptor-associated kinase, IRAK1, IRAK2 adaptor proteins, and tumour necrosis factor (TNF) targeting protein receptor 6, which is a regulator of the TNF signalling pathway. In addition, miRNA-146a affects gene expression through multiple signalling pathways, such as TNF, NF-κB and MEK-1/2, and JNK-1/2. Studies have been carried out to determine the effect of miRNA-146a on cancer pathogenesis, revealing its involvement in the synthesis of stem cells, which contributes to tumourigenesis. In this review, we focus on recent discoveries that highlight the significant role played by miRNA-146a in regulating various defence mechanisms and oncogenesis. The aim of this review article is to systematically examine miRNA-146a's impact on the control of signalling pathways involved in oncopathology, immune system development, and the corresponding response to therapy.
Assuntos
Doenças Autoimunes , MicroRNAs , Humanos , Carcinogênese , Transformação Celular Neoplásica , Proteínas Adaptadoras de Transdução de Sinal , Doenças Autoimunes/genética , MicroRNAs/genéticaRESUMO
The environment is seldom optimal for plant growth and changes in abiotic and biotic signals, including temperature, water availability, radiation and pests, induce plant responses to optimise survival. The New Zealand native plant species and close relative to Arabidopsis thaliana, Pachycladon cheesemanii, grows under environmental conditions that are unsustainable for many plant species. Here, we compare the responses of both species to different stressors (low temperature, salt and UV-B radiation) to help understand how P. cheesemanii can grow in such harsh environments. The stress transcriptomes were determined and comparative transcriptome and network analyses discovered similar and unique responses within species, and between the two plant species. A number of widely studied plant stress processes were highly conserved in A. thaliana and P. cheesemanii. However, in response to cold stress, Gene Ontology terms related to glycosinolate metabolism were only enriched in P. cheesemanii. Salt stress was associated with alteration of the cuticle and proline biosynthesis in A. thaliana and P. cheesemanii, respectively. Anthocyanin production may be a more important strategy to contribute to the UV-B radiation tolerance in P. cheesemanii. These results allowed us to define broad stress response pathways in A. thaliana and P. cheesemanii and suggested that regulation of glycosinolate, proline and anthocyanin metabolism are strategies that help mitigate environmental stress.