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1.
Mar Pollut Bull ; 204: 116513, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795464

RESUMO

The present study aims to combat the problem of oil in water pollution via its separation using a superhydrophobic copper mesh. An ecofriendly superhydrophobic copper mesh with a water contact angle of 166 ± 2° is developed by a facile two-step process (electrodeposition followed by coating). The coated mesh with mechanical robustness, chemical endurance and thermal stability is a promising choice for real-world conditions. Additionally, its resistance to corrosion in harsh chemical environments ensures its long-term durability. With a separation efficiency of 99.9 %, the coated mesh serves as an efficient medium for oil-water separation. It can be used as a reusable filtering medium with high separation efficiency in alkali and neutral environments. Besides, it is also competent for continuous oil-water separation and collection of oil from wastewater. Thus, the above study clearly manifests that the coated mesh holds tremendous potential for large-scale oil spill cleanup.


Assuntos
Cobre , Recuperação e Remediação Ambiental , Interações Hidrofóbicas e Hidrofílicas , Poluição por Petróleo , Poluentes Químicos da Água , Cobre/química , Recuperação e Remediação Ambiental/métodos , Poluentes Químicos da Água/análise , Galvanoplastia
2.
J Biol Chem ; 300(6): 107328, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679332

RESUMO

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes. Here, we demonstrate that obese AT microenvironment triggers the release of miR-210-3p microRNA-loaded extracellular vesicles from adipose tissue macrophages, which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity. Moreover, EVs collected from Dicer-silenced miR-210-3p-overexpressed bone marrow-derived macrophages induce glucose intolerance and IR in lean mice. Mechanistically, miR-210-3p interacts with the 3'-UTR of GLUT4 mRNA and silences its expression, compromising cellular glucose uptake and insulin sensitivity. Therapeutic inhibition of miR-210-3p in VAT notably rescues high-fat diet-fed mice from obesity-induced systemic glucose intolerance. Thus, targeting adipose tissue macrophage-specific miR-210-3p during obesity could be a promising strategy for managing IR and type 2 diabetes.


Assuntos
Transportador de Glucose Tipo 4 , Resistência à Insulina , Macrófagos , MicroRNAs , Obesidade , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Obesidade/metabolismo , Obesidade/genética , Obesidade/patologia , Macrófagos/metabolismo , Camundongos , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Masculino , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Humanos , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/metabolismo , Intolerância à Glucose/genética , Intolerância à Glucose/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia
3.
Adv Radiat Oncol ; 9(5): 101446, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38550366

RESUMO

Purpose: The head and neck cancer (HNC) literature is rife with reports of differences in planned versus actual radiation doses to the parotid gland (PG) due to changes in anatomy during the course of radiation therapy. We prospectively studied and quantified changes in planned and delivered doses due to weight loss and changes in lateral neck dimensions. Methods and Materials: Sixty patients were enrolled in this prospective non-randomized observational study. The inclusion criterion was having a newly diagnosed, histologically proven squamous cell carcinoma of HNC. Weight loss (WL) and change in lateral neck dimensions (LND) were assessed weekly, and new hybrid plans were generated using interval replanning CT scans. Dose variations were monitored and extrapolated for replanning CT scans and correlated with WL and change in LND. Results: The Pearson correlation coefficients for WL and difference in Dmean of ipsilateral and contralateral PG was 0.3292 (P = .0124) and 0.4232 (P = .0010), respectively. There was significantly higher change in the Dmean of bilateral PG (Ipsilateral(I) > contralateral(C)) in patients who experienced WL of >5%. Change in LND correlated with difference in Dmean of ipsilateral PG at 0.4829 (P = .0001) and difference in D50 at 0.4146 (P < .0013). Contralateral PG correlated with difference in Dmean at 0.5952 (P < .0001). The difference in Dmean for ipsilateral PG was 1.8535 Gy for those showing reduction in LND of >1 cm compared with 0.8596 Gy (P = .0091) for those who had ≤1 cm reduction in LND. Conclusions: Either WL of >5% or reduction in LND of >1 cm can be used as an external parameter to help select patients who might benefit most from replanning and adaptive radiation therapy.

4.
Mar Pollut Bull ; 200: 116062, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290364

RESUMO

The present study aims to address the issue of oil in water pollution by application of a superhydrophobic cotton fabric. The superhydrophobic cotton fabric with a water contact angle of 158 ± 2°, is developed by a solution immersion technique using zirconium dioxide (ZrO2) nanoparticles and hexadecyltrimethoxysilane. The synthesis parameters such as concentration, curing temperature, and immersion time were optimized using Box-Behnken design method. With mechanical durability, chemical resilience and thermal stability, the coated fabric can separate different oil-water mixtures with an efficiency of 99.9 %. The coated fabric can also be reused for 50 separation cycles in acidic and neutral medium. Besides, droplet dynamic behavior of oil-water mixture has also been studied to ascertain the effect of mixture impact velocities on separation performance. Additionally, coated fabric possesses self-cleaning feature, which makes it viable for muddy oil-water separation. Prepared coated fabric holds tremendous potential for industrial use and oil-water separation in extreme conditions.


Assuntos
Indústrias , Têxteis , Água , Poluição da Água , Interações Hidrofóbicas e Hidrofílicas
5.
Surg Endosc ; 38(2): 659-670, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38012444

RESUMO

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.


Assuntos
Transtornos de Deglutição , Acalasia Esofágica , Esofagite , Miotomia de Heller , Laparoscopia , Humanos , Acalasia Esofágica/cirurgia , Acalasia Esofágica/diagnóstico , Azia/cirurgia , Transtornos de Deglutição/etiologia , Miotomia de Heller/métodos , Cárdia/cirurgia , Qualidade de Vida , Laparoscopia/métodos , Esofagite/etiologia , Resultado do Tratamento
6.
Mar Pollut Bull ; 197: 115701, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890316

RESUMO

Ecosystems suffer from increased oil exploitation and frequent oil spills, which calls for effective, environment-friendly, and economically viable solutions. To address this, abandoned gunny sacks as the concerned jute fabric were superhydrophobically (water contact angle ∼159°) modified, incorporating titanium dioxide (TiO2) nanoparticles and hexadecyltrimethoxysilane (HDTMS), rendering a facile drop casting procedure. The modified superhydrophobic-superoleophilic jute fabric has been identified as a high-performance filter with superior reusability that can separate oil-water mixtures in challenging environmental conditions (including potent acidic, alkaline, highly saline, aqueous, frigid, and blistering water environments) while maintaining high separation efficiency. In continuation, static conditions indulging a batch and continuous oil separation performance and dynamic conditions stimulating turbulence in the oil-water mixture were proficiently carried out, mimicking real-world circumstances. As a result, the modified jute fabric has the advantages of high separation efficiency, stable recyclable properties, and outstanding durability, highlighting its enormous potential for use in practical applications.


Assuntos
Nanopartículas , Poluição por Petróleo , Ecossistema , Água , Interações Hidrofóbicas e Hidrofílicas
7.
J Minim Access Surg ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37843170

RESUMO

Intussusception in adults represents 1% of bowel obstructions and up to 0.02% of all hospital admissions. Amongst these, colo-colic intussusception of the descending colon forms the rarest of causes due to the fixed nature of the descending colon. Most of adult intussusceptions follow a lead point and are commonly due to colonic malignancy which may get missed on pre-operative evaluation. Surgery is usually warranted as these patients are usually symptomatic and at risk of vascular compromise, leading to perforations and obscure malignancies. We present a case of laparoscopic limited hemicolectomy and primary anastomosis in a middle-aged male who presented with colo-colic intussusception, which appeared to be following a malignant mass on imaging and lipoma on colonoscopic biopsy done twice. Keeping in mind the possibility of a malignant lead point, no attempt was made to reduce the intussusception and a vessel first approach with 5 cm margin on either side was performed.

8.
Clin Pharmacol Ther ; 114(2): 446-458, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37278090

RESUMO

Cannabis use during pregnancy may cause fetal toxicity driven by in utero exposure to (-)-∆9 -tetrahydrocannabinol (THC) and its psychoactive metabolite, (±)-11-hydroxy-∆9 -THC (11-OH-THC). THC concentrations in the human term fetal plasma appear to be lower than the corresponding maternal concentrations. Therefore, we investigated whether THC and its metabolites are effluxed by placental transporters using the dual cotyledon, dual perfusion, term human placenta. The perfusates contained THC alone (5 µM) or in combination (100-250 nM) with its metabolites (100 nM or 250 nM 11-OH-THC, 100 nM COOH-THC), plus a marker of P-glycoprotein (P-gp) efflux (1 or 10 µM saquinavir), and a passive diffusion marker (106 µM antipyrine). All perfusions were conducted with (n = 7) or without (n = 16) a P-gp/BCRP (breast-cancer resistance protein) inhibitor, 4 µM valspodar. The maternal-fetal and fetal-maternal unbound cotyledon clearance indexes (m-f-CLu,c,i and f-m-CLu,c,i ) were normalized for transplacental antipyrine clearance. At 5 µM THC, the m-f-CLu,c,i , 5.1 ± 2.1, was significantly lower than the f-m-CLu,c,i , 13 ± 6.1 (P = 0.004). This difference remained in the presence of valspodar or when the lower THC concentrations were perfused. In contrast, neither metabolite, 11-OH-THC/COOH-THC, had significantly different m-f-CLu,c,i vs. f-m-CLu,c,i . Therefore, THC appears to be effluxed by placental transporter(s) not inhibitable by the P-gp/BCRP antagonist, valspodar, while 11-OH-THC and COOH-THC appear to passively diffuse across the placenta. These findings plus our previously quantified human fetal liver clearance, extrapolated to in vivo, yielded a THC fetal/maternal steady-state plasma concentration ratio of 0.28 ± 0.09, comparable to that observed in vivo, 0.26 ± 0.10.


Assuntos
Troca Materno-Fetal , Placenta , Gravidez , Humanos , Feminino , Placenta/metabolismo , Dronabinol , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Neoplasias/metabolismo , Antipirina/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
9.
APL Bioeng ; 7(2): 026109, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37252678

RESUMO

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have the potential to become powerful tools for disease modeling, drug testing, and transplantation; however, their immaturity limits their applications. Transcription factor (TF) overexpression can improve hPSC-CM maturity, but identifying these TFs has been elusive. Toward this, we establish here an experimental framework for systematic identification of maturation enhancing factors. Specifically, we performed temporal transcriptome RNAseq analyses of progressively matured hPSC-derived cardiomyocytes across 2D and 3D differentiation systems and further compared these bioengineered tissues to native fetal and adult-derived tissues. These analyses revealed 22 TFs whose expression did not increase in 2D differentiation systems but progressively increased in 3D culture systems and adult mature cell types. Individually overexpressing each of these TFs in immature hPSC-CMs identified five TFs (KLF15, ZBTB20, ESRRA, HOPX, and CAMTA2) as regulators of calcium handling, metabolic function, and hypertrophy. Notably, the combinatorial overexpression of KLF15, ESRRA, and HOPX improved all three maturation parameters simultaneously. Taken together, we introduce a new TF cocktail that can be used in solo or in conjunction with other strategies to improve hPSC-CM maturation and anticipate that our generalizable methodology can also be implemented to identify maturation-associated TFs for other stem cell progenies.

10.
Indian J Orthop ; 57(4): 552-564, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37006739

RESUMO

Introduction: Humerus shaft nonunions are very disabling and challenging to treat. The current study aims to analyse the rate of union and the incidence of complications following a consistent protocol in treating humerus shaft nonunion. Methodology: We did a retrospective analysis of 100 patients with humerus shaft nonunion treated over an eight-year period from 2014 to 2021. The mean age was 42 years (range 18-75 years). There were 53 male and 47 female patients. The average time interval from injury to nonunion surgery was 23 months (range 3 months to 23 years). The series included 12 recalcitrant nonunions and 12 patients with septic nonunion. All patients underwent freshening of fracture edges to increase the contact surface area, stable fixation with a locking plate and intramedullary iliac crest bone grafting. Infective nonunions were treated in a staged manner, following a similar treatment protocol after the elimination of infection in the first stage. Results: Complete union was achieved in 97% of the patients with a single procedure. One patient achieved union after an additional procedure, while two patients were lost to further follow-up. The mean time to union was 5.7 months (range 3-10 months). Three patients (3%) had postoperative radial nerve palsy, which recovered completely within 6 months. Three patients (3%) had a superficial surgical site infection, while one patient (1%) developed a deep infection. Conclusion: Intramedullary cancellous autologous grafts combined with stable fixation by compression plating achieve a high union rate with minimal complications. Level of Evidence: III. Level of Clinical Care: Level I Tertiary trauma centre.

11.
Environ Sci Pollut Res Int ; 30(10): 25181-25192, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34846664

RESUMO

In recent years, special attention has been given to emission research that led to the deposition of toxicants from road traffic. Thus, it is imperative to focus on heavy metal (HM) stressors in food items, their source contribution, and health risk assessment providing insight into their spatial role at the population level. In this study, heavy metal in the street vended noodles was studied while correlating the quality of noodle with different environmental origins. The samples were prepared using acid digestion and analysed by flame atomic absorption spectrophotometer, except Hg which was analysed by direct mercury analyser. The results showed that some heavy metals like Cr, Pb, Mn, Cd, and Hg exceed their permissible limits established by the international legislation for food products. In the noodle samples, the concentration of heavy metal ranged from < 0.1 to 0.904 mg/kg for Pb, < 0.09 to 0.843 mg/kg for Ni, < 0.004 to 0.201 mg/kg for Cd, < 0.0001 to 0.004 mg/kg for Hg, < 0.01 to 1.388 mg/kg for Cu, < 0.015 to 8.049 mg/kg for Mn, and < 0.02 to 16.514 mg/kg for Cr. Noodle samples vended on high traffic density streets are directly associated with increased HM content due to atmospheric deposition from the surrounding. Source apportionment study determines that HM contamination belongs to the same source of origin, except Cr. Based on the cluster analysis, these samples fall into three major groups that were further validated by the canonical discriminant function. Health risk prediction by Monte Carlo simulation revealed an elevated non-carcinogenic health hazard risk to consumers with a hazard index (HI) shift from 71 to 75%. Health hazard analysis showed that consumers of high traffic density street vended food are at higher risk of developing health-related issues. This study is important to evaluate the health risk of the population exposed to heavy metals due to ingestion of street vended food.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Cádmio/análise , Chumbo/análise , Metais Pesados/análise , Medição de Risco , Mercúrio/análise , Monitoramento Ambiental , China , Poluentes do Solo/análise
12.
Thorac Cardiovasc Surg ; 70(7): 589-595, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35263793

RESUMO

OBJECTIVES: The objective of this study was to present the procedural details and digital subtraction angiography (DSA) findings of perioperative chest-wall collateral embolization (PCCE) and compare intraoperative blood loss in patients of pulmonary aspergilloma (PA) undergoing lung resection with and without PCCE. MATERIALS AND METHODS: Since November 2017, we have performed PCCE in 17 patients (14 males, three females, age 34.41 ± 12.85 years) before surgery for PA (embolization group). Retrospective evaluation of these patients was done, DSA findings were noted, and perioperative parameters (surgical approach, extent of resection, operative time, blood loss, blood transfusion, morbidity grade, and length of post-operative stay) were compared with a comparative cohort of 24 patients of PA (21 males, three females, mean age 36.13 ± 12.58 years) who underwent thoracic surgery without PCCE (May 2013-November 2017) (control group) using the Mann-Whitney U test. RESULTS: A total of 55 arteries were embolized in 17 patients (mean 3.23 arteries per patient). Technical success could be achieved in all patients without any procedure-related complications. The most common arteries embolized were posterior intercostal arteries (29) followed by costocervical trunk (10), superior thoracic (8), lateral thoracic (5), and internal thoracic arteries (3). The mean blood loss was significantly lower in the embolization group compared with the control group (676.47 vs. 1,264.58 mL, p = 0.015). Within the embolization group, patients who underwent video-assisted thoracoscopic surgery had even lower blood loss compared with open surgery cases (466 vs. 887.50 mL, p-value = 0.046). CONCLUSION: PCCE is a simple and safe procedure, useful in reducing intra-operative blood loss in patients undergoing surgery for peripherally located PA.


Assuntos
Perda Sanguínea Cirúrgica , Embolização Terapêutica , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento , Adulto Jovem
13.
Surg Laparosc Endosc Percutan Tech ; 32(3): 299-304, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35034067

RESUMO

BACKGROUND: Symptomatic evaluation using Eckardt score and achalasia-specific health-related quality-of-life and physiological evaluation using timed barium examination (TBE) and high-resolution manometry is integral to the diagnosis of achalasia. However, the correlation of physiological outcomes with symptomatic outcomes and their role in routine follow-up after laparoscopic Heller cardiomyotomy (LHCM) is controversial. In this study, we evaluated the role of physiological testing in achalasia patients undergoing LHCM and its correlation with symptomatic evaluation. MATERIALS AND METHODS: Case records of patients undergoing LHCM for achalasia between January 2017 and March 2020 were reviewed for symptom scores (Eckardt score and achalasia-specific health-related quality-of-life) and physiological parameters [5-min column height on TBE and median integrated relaxation pressure (IRP) on high-resolution manometry]. Sixty-one patients with complete data in the preoperative period and on follow-up were included in the study. The data was analyzed for symptomatic and physiological outcomes and their correlation using paired t test and the Spearman correlation test. RESULTS: At a median follow-up of 16 months following LHCM, there was a significant improvement in Eckardt score (7.03±1.53 to 0.93±1.10, P<0.001), achalasia-specific health-related quality-of-life (58.34±7.81 to 14.57±13.45, P<0.001), column height on TBE (115.14±46.9 to 27.89±34.31, P<0.001) and IRP (23.95±8.26 to 4.61±4.11, P<0.001). Eckardt score correlated significantly with achalasia-specific health-related quality-of-life scores preoperatively (ρ=0.410, P<0.001) and on follow-up (ρ=0.559, P<0.001). There was no correlation between symptomatic parameters and physiological parameters. CONCLUSIONS: In patients of achalasia, LHCM leads to significant improvement in symptomatic and physiological parameters. Symptom scores correlate among themselves but not with physiological scores. Thus, physiological testing may not be needed for routine follow-up.


Assuntos
Acalasia Esofágica , Miotomia de Heller , Cárdia/cirurgia , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/cirurgia , Humanos , Manometria , Resultado do Tratamento
14.
J Hand Surg Asian Pac Vol ; 27(6): 1038-1042, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36606352

RESUMO

Non-union of the clavicle in the paediatric population is extremely rare. Some anecdotal case reports show non-union following clavicle fracture. However, we could not find any report of non-union following osteotomy for brachial plexus surgery. We report non-union of clavicle following its osteotomy for brachial plexus exploration surgery in a 6-month child. We present successful management of the clavicle non-union in this patient and propose preventive steps. Level of Evidence: Level V (Therapeutic).


Assuntos
Neuropatias do Plexo Braquial , Plexo Braquial , Criança , Humanos , Lactente , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/cirurgia , Plexo Braquial/cirurgia , Osteotomia/efeitos adversos , Paralisia
15.
PLoS One ; 16(11): e0258645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780495

RESUMO

All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays.


Assuntos
Biologia Computacional , Mapeamento de Epitopos , SARS-CoV-2/imunologia , Proteínas Estruturais Virais/imunologia , Sequência de Aminoácidos , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Bases de Dados como Assunto , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Modelos Moleculares , Conformação Proteica , Reprodutibilidade dos Testes , Proteínas Estruturais Virais/química
16.
Indian J Thorac Cardiovasc Surg ; 37(5): 558-564, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34511764

RESUMO

Complex long-standing diaphragmatic hernia presenting in adults is often managed through an open approach. Minimal invasive approach by either laparoscopy or thoracoscopy is limited by its ability to tackle these complex hernias with large defects and thoraco-mediastinal adhesions. Thus, standard laparoscopic or thoracoscopic approach is associated with high conversion to open approach. We herein describe a novel combined thoraco-laparoscopic approach to repair complex diaphragmatic hernias in a series of three adults.

17.
Gene ; 803: 145892, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34375633

RESUMO

The p53 tumor suppressor protein maintains the genome fidelity and integrity by modulating several cellular activities. It regulates these events by interacting with a heterogeneous set of response elements (REs) of regulatory genes in the background of chromatin configuration. At the p53-RE interface, both the base readout and torsional-flexibility of DNA account for high-affinity binding. However, DNA structure is an entanglement of a multitude of physicochemical features, both local and global structure should be considered for dealing with DNA-protein interactions. The goal of current research work is to conceptualize and abstract basic principles of p53-RE binding affinity as a function of structural alterations in DNA such as bending, twisting, and stretching flexibility and shape. For this purpose, we have exploited high throughput in-vitro relative affinity information of responsive elements and genome binding events of p53 from HT-Selex and ChIP-Seq experiments respectively. Our results confirm the role of torsional flexibility in p53 binding, and further, we reveal that DNA axial bending, stretching stiffness, propeller twist, and wedge angles are intimately linked to p53 binding affinity when compared to homeodomain, bZIP, and bHLH proteins. Besides, a similar DNA structural environment is observed in the distal sequences encompassing the actual binding sites of p53 cistrome genes. Additionally, we revealed that p53 cistrome target genes have unique promoter architecture, and the DNA flexibility of genomic sequences around REs in cancer and normal cell types display major differences. Altogether, our work provides a keynote on DNA structural features of REs that shape up the in-vitro and in-vivo high-affinity binding of the p53 transcription factor.


Assuntos
DNA/metabolismo , Análise de Sequência de DNA/métodos , Proteína Supressora de Tumor p53/metabolismo , Sítios de Ligação , Cromossomos Humanos/genética , DNA/química , Regulação da Expressão Gênica , Humanos , Regiões Promotoras Genéticas , Elementos de Resposta
18.
Clin Pharmacol Ther ; 109(3): 667-675, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32885413

RESUMO

The human blood-brain barrier (BBB) transporter P-gp can efflux amyloid-ß (Aß) out of the central nervous system (CNS). Aß is thought to be the causative agent for Alzheimer's disease (AD). Using positron emission tomography imaging, we have shown that BBB P-gp activity is reduced in AD, as quantified by the in vivo brain distribution of the P-gp probe [11 C]-verapamil. Therefore, the aim of this study was to determine whether this reduced BBB P-gp activity in AD was due to decreased P-gp abundance at the BBB. Using targeted proteomics, we quantified the abundance of P-gp and other drug transporters in gray matter brain microvessels isolated from 43 subjects with AD and 38 age-matched controls (AMCs) from regions affected by AD (hippocampus and the parietal lobe of the brain cortex) and not affected by AD (cerebellum). First, P-gp abundance was decreased in the BBB of the hippocampus vs. the cerebellum in both subjects with AD and AMCs, and therefore was not AD-related. In addition, gray matter BBB abundance of P-gp (and of other transporters) in the hippocampus and the parietal lobe was not different between AD and AMC. The gray matter BBB abundance of all drug transporters decreased with age, likely due to age-dependent decrease in the density of brain microvessels. Collectively, the observed reduced in vivo cerebral BBB P-gp activity in AD cannot be explained by reduced abundance of P-gp at the BBB. Nevertheless, the drug transporter abundance at the human gray matter BBB data provided here can be used to predict brain distribution of drugs targeted to treat CNS diseases, including AD.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Doença de Alzheimer/metabolismo , Barreira Hematoencefálica/metabolismo , Substância Cinzenta/irrigação sanguínea , Microvasos/metabolismo , Proteômica , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Transporte Biológico , Barreira Hematoencefálica/diagnóstico por imagem , Estudos de Casos e Controles , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Feminino , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Microvasos/diagnóstico por imagem , Proteínas de Neoplasias/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Tomografia por Emissão de Pósitrons , Verapamil/metabolismo , Adulto Jovem
20.
Int J Surg Case Rep ; 72: 298-300, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32563089

RESUMO

INTRODUCTION: Femoral hernia is infrequently encountered in surgical practice and is even rare in patients with liver cirrhosis. Recurrent pain adds to the existing morbidity and affects the quality of life of these patients. Management of such cases had rather high rates of morbidity and mortality owing to hepatic decompensation. However, more recent studies have shown a significant improvement of the quality of life and improved rates of morbidity in cirrhotic patients with inguinal hernias post repair. These studies all included open hernia repair with preperitoneal approach with improved results in terms of morbidity and lower rates of recurrence postoperatively. However, when compared to laparoscopic repairs these have more postoperative complications, complication related re-operations, pain and recurrence rates. Keeping these in mind, the laparoscopic approach was considered in our patient which has not been described yet in literature for femoral hernia. The report is in line with the SCARE criteria. (Agha et al. (2018) [1]) The case report is registered with research registry (UID researchregistry5467). PRESENTATION OF CASE: A 40 year old female patient with Child B cirrhosis of liver with ascites was operated for a symptomatic left uncomplicated femoral hernia using standard three port laparoscopic total extraperitoneal repair with prolene mesh. She was discharged on postoperative day 2. She developed ascitic leak from the hypogastric port site in the late postoperative period which was managed conservatively. The patient has remained stable without recurrence at one year follow up. CONCLUSION: Laparoscopic TEP may be a safe option with no major adverse events in symptomatic femoral hernias. Further studies are needed to ascertain its role.

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