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1.
Environ Res ; 249: 118463, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38342201

RESUMO

During gasification the kinetic and thermodynamic parameter depend on both the feedstock and the process conditions. As a result, one needs to enhance the understanding of how to model numerically these parameters using thermogravimetric analyzer. Consequently, there exists a pressing need to computationally devise gasification model that can efficiently account to thermodynamic and kinetic parameter from thermogravimetric data. In this study, we numerically model gasification process kinetic and thermodynamic parameters, which vary with feedstock and operational conditions. Our novel approach involves creating an ANN model in MATLAB using a carefully optimized 8-20-20-10-1 architecture. Based on thermogravimetric analyzer (TGA) data, this model uniquely predicts critical kinetic (activation energy, pre-exponential factor) and thermodynamic parameters (entropy, enthalpy, Gibbs free energy, ignition index, boiling temperature). Our ANN model, trained on over 80 diverse samples with the Levenberg-Marquardt algorithm, excels at prediction, with an MSE of 6.185e-6 and an R2 value exceeding 0.9996, ensuring highly accurate estimates. Based on time, temperature, heating rate, and elemental composition, it accurately predicts thermal degradation. The model can predict TGA curves for many materials, demonstrating its versatility. For instance, it accurately estimates the activation energy for pure glycerol at 73.84 kJ/mol, crude glycerol at 67.55 kJ/mol, 12.12 kJ/mol for coal, and 111.3 kJ/mol for wood. These results, particularly for Kissinger-validated glycerol, demonstrate the model's versatility and efficacy in various gasification scenarios, making it a valuable tool for thermochemical conversion studies.


Assuntos
Redes Neurais de Computação , Termogravimetria , Termogravimetria/métodos , Termodinâmica , Cinética , Modelos Químicos
2.
Pediatr Surg Int ; 40(1): 171, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958763

RESUMO

PURPOSE: Split abdominal wall muscle flap (SAWMF) is a technique to repair large defects in congenital diaphragmatic hernia (CDH). A possible objection to this intervention could be any associated abdominal muscle weakness. Our aim is to analyze the evolution of this abdominal muscle wall weakness. METHODS: Retrospective review of CDH repair by SAWMF (internal oblique muscle and transverse) from 2004 to 2023 focusing on the evolution of muscle wall weakness. RESULTS: Eighteen neonates of 148 CDH patients (12,1%) were repaired using SAWMF. Mean gestational age and birth weight were 35.7 ± 3.5 weeks and 2587 ± 816 g. Mean lung-to-head ratio was 1.49 ± 0.28 and 78% liver-up. Seven patients (38%) were prenatally treated by tracheal occlusion. Ninety-four percent of the flaps were used for primary repair and one to repair a recurrence. One patient (5.6%) experienced recurrence. Abdominal muscle wall weakness was present in the form of a bulge. Resolution of weakness at 1, 2 and 3 years was 67%, 89% and 94%, respectively. No patient required treatment for weakness or died. CONCLUSIONS: Abdominal muscular weakness after a split abdominal wall muscle flap repair is not a limitation for its realization since it is asymptomatic and presents a prompt spontaneous resolution. LEVEL OF EVIDENCE: IV.


Assuntos
Músculos Abdominais , Parede Abdominal , Hérnias Diafragmáticas Congênitas , Debilidade Muscular , Retalhos Cirúrgicos , Humanos , Hérnias Diafragmáticas Congênitas/cirurgia , Hérnias Diafragmáticas Congênitas/complicações , Recém-Nascido , Estudos Retrospectivos , Masculino , Feminino , Parede Abdominal/cirurgia , Debilidade Muscular/etiologia , Debilidade Muscular/cirurgia , Músculos Abdominais/cirurgia , Herniorrafia/métodos , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento
3.
J Asian Nat Prod Res ; : 1-22, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287957

RESUMO

The venom of the Odontobuthus doriae scorpion, prevalent in East Asia and Iran, has not been fully characterized. This study provides the first proteomic profile of O. doriae venom to explore its potential as a medical. 2D-PAGE analysis revealed 96 protein spots with isoelectric points from 3 to 9 and molecular weights between 6.6 to 205 kDa. Fourteen toxin fractions were isolated via HPLC, and SDS-PAGE showed seven protein bands ranging from 3.8 to 182 kDa. MALDI-TOF MS identified Peptide 1 and Peptide 2, resembling Hemoglobin beta-2 chain and Chaperonin HSP60 and suggest potential therapeutic applications for P1 and P2.

4.
Funct Integr Genomics ; 23(2): 186, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37243790

RESUMO

Osteoporosis is a common disease, especially among the elderly. This study aimed to comprehensively examine the roles of immune microenvironment in osteoporosis pathogenesis. Expression profiles of GSE35959, GSE7158, and GSE13850 datasets were used to analyze differential expression and identify hub genes related to immune features. Based on the single-cell RNA sequencing (scRNA-seq) data of an osteoporosis patient, different cell types were classified and the relation between immune environment and osteoporosis was explored. Twelve hub genes significantly associated with immune features were selected and 11 subgroups were defined using scRNA-seq data. The expression of two hub genes (CDKN1A and TEFM) was greatly altered during the transformation from mesenchymal stem cells (MSCs) to osteoblasts. Chemokines and chemokine receptors were differentially enriched in different cell types. CXCL12 was high-expressed in MSCs. This study emphasized that immune microenvironment played a critical role in the pathogenesis of osteoporosis. Chemokines and chemokine receptors can modify cell development and affect the interactions among different cell types, leading to unbalanced bone remodeling.


Assuntos
Osteoporose , Humanos , Idoso , Células Cultivadas , Osteoporose/genética , Quimiocinas/genética , Receptores de Quimiocinas/genética , Análise de Sequência de RNA
5.
J Biochem Mol Toxicol ; 36(11): e23187, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35920545

RESUMO

Lung cancer, one of the most common cancer is a cause of concern associated with cancer-related mortality. Benzo[a]pyrene [B(a)P], a potent carcinogen as well as an environmental contaminant is reported to be found in cigarette smoke among various sources. The present study focuses on the chemopreventive potential of Diosmin against B[a]P-induced lung carcinogenesis and its possible mechanism in male Swiss Albino mice (SAM). SAM were treated orally with Diosmin (200 mg/kg b.w.) for 16 weeks and/or B[a]P (50 mg/kg b.w) for a period of 4 weeks. B[a]P treated cancerous mice showed increased peroxidation of membrane lipid as well as a decrease in the level/activity of antioxidant proteins. Cancerous mice also showed an increased level of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE). Diosmin treatment, however, leads to decreased peroxidation of lipids, increased antioxidant proteins as well decrease in the level of CEA and NSE. B[a]P-induced cancerous animals also exhibited increased expression of cyclic AMP response element-binding protein (CREB), COX2 as well as prostaglandin-E2 (PGE2) while Diosmin-treated mice were found to have an ameliorative effect. Histopathological results further confirm the protective effect of Diosmin in averting B[a]P-induced pathological alterations of lung tissue. Overall, our results suggest Diosmin exerts its chemopreventive potential possibly via targeting the CREB/cyclooxygenase-2 (COX-2)/PGE2 pathway thereby repressing inflammation.


Assuntos
Diosmina , Neoplasias Pulmonares , Masculino , Camundongos , Animais , Benzo(a)pireno/toxicidade , Diosmina/efeitos adversos , Diosmina/metabolismo , Antígeno Carcinoembrionário/metabolismo , Antioxidantes/farmacologia , Dinoprostona/metabolismo , Pulmão/metabolismo , Carcinogênese , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/metabolismo , Ciclo-Oxigenase 2/metabolismo
6.
Environ Toxicol ; 37(9): 2153-2166, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35567572

RESUMO

1,2-Dimethylhydrazine (DMH), a colon-specific environmental toxicant is one among the carcinogen responsible for the cause of colon cancer. The present study was designed to evaluate the protective effect of Hesperetin (HST) against colon toxicity induced by DMH in Wistar rats. HST, a flavonoid widely found in citrus fruits possesses several biological activities including anti-microbial, anti-oxidant properties among others. A single dose of DMH (40 mg/kg body weight) was administered subcutaneously on 1st day for induction of colon toxicity followed by oral treatment with HST at a dose of 20 mg/kg bodyweight for 14 consecutive days. DMH administration leads to excessive ROS generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Our result showed HST significantly ameliorates DMH-induced lipid peroxidation and also substantially increases the activity/level of various anti-oxidant proteins (GR, GPx, GST, GSH, and SOD). HST was also found to reduce the expression of inflammatory proteins (TNF-α, IL-6, i-NOS, COX-2, NF-kB-p65), goblet cell disintegration as well as mucin depletion (sulfo and sialomucin) in the colon that was found to be elevated upon administration of DMH. Our histological results further provide confirmation of the protective role of HST against DMH-induced pathological alterations. The results of the present study demonstrate supplementation of HST is beneficial in ameliorating DMH-induced toxicity by suppressing oxidative stress, inflammation, goblet cell disintegration as well mucin depletion in the colon of Wistar rats.


Assuntos
Neoplasias do Colo , Hesperidina , Estresse Oxidativo , 1,2-Dimetilidrazina/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Colo/metabolismo , Neoplasias do Colo/patologia , Glutationa/metabolismo , Hesperidina/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Mucinas/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
7.
J Pak Med Assoc ; 72(5): 878-881, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35713048

RESUMO

OBJECTIVE: To assess musculoskeletal disorders among male cricketers in an urban centre. METHODS: The cross-sectional study was conducted from October to November 2020 in Lahore, Pakistan, and comprised male cricket players aged 10-25 years playing in four domestic clubs. Data was collected about musculoskeletal disorders experienced during the preceding 12 months using the Extended Nordic Musculoskeletal Questionnaire. Data was analysed using SPSS 22. RESULTS: Of the 89 players with a mean age of 19.24±3.12 years, 35(39.3%) were bowlers, 26(29.2%) were batsmen, 17(19.1%) were all-rounders, and 11(12.4%) were wicketkeepers. The anatomical distribution of disorder was lower-back 68(76.4%), shoulder 40(44.9%), neck 39(43.8%), upper-back 37(41.6%), knees 31(34.8%), ankle/feet 29(32.6%), thighs 27(30.3%), wrist/hands 18(20.2%), and elbows 17(19.1%). There were 22(24.7%) players who had at any time seen a doctor or a physiotherapist, while 24(27%) players had a history of taking sick leave. CONCLUSIONS: The most affected anatomical segments were lower-back, shoulder, knee, ankle and upper-back.


Assuntos
Doenças Musculoesqueléticas , Doenças Profissionais , Adolescente , Adulto , Estudos Transversais , Humanos , Masculino , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
8.
Public Health Nutr ; 24(7): 1619-1628, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33494852

RESUMO

OBJECTIVE: This study aimed to identify and rank the different aspects of households' vulnerability to food insecurity. DESIGN: The data were collected by a standard online questionnaire. The Household Food Insecurity Access Scale was used to assess food insecurity levels, and first-order structural equation modelling was applied to determine factors that affect food insecurity. Seven dimensions of vulnerability were measured: economic, social, cultural, human, physical, psychology and information, using thirty-seven items extracted from the related literature review. SETTING: This study was implemented in Tehran province in Iran. PARTICIPANTS: The sample included 392 families residing in Tehran province which was determined using random sampling. RESULTS: About 61 % of the total sample faced food insecurity, at marginal, moderate and severe levels. Economic, psychological and human aspects of vulnerability had the highest effect on food insecurity during the initial COVID-19 lockdown. CONCLUSIONS: Authorities and policymakers must provide economic and financial support to vulnerable households. Abolition of US economic and financial sanctions imposed on Iran must be implemented to battle with COVID-19 in this country.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis/estatística & dados numéricos , Características da Família , Insegurança Alimentar , Populações Vulneráveis/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Irã (Geográfico) , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Inquéritos e Questionários
9.
Environ Toxicol ; 32(2): 619-629, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27028940

RESUMO

Rheumatoid arthritis (RA) is the most common type of chronic inflammatory disease which is triggered by dysfunction in the immune system which in turn affects synovial joints. Current treatment of RA with NSAIDs and DMRDs is limited by their side effect. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and anti-inflammatory activities underlying the anti-RA effect of Yohimbine hydrochloride (YCL) in collagen induced arthritis (CIA) in Wistar rats. The YCL was administered at doses of 5 and 10 mg kg-1 body weight once daily for 28 days. The effects of treatment in the rats were assessed by biochemical parameter (articular elastase, LPO, GSH, catalase, SOD), hematological parameter (ESR, WBC, C-reactive protein (CRP), immunohistochemical expression (COX2, TNF-α, and NF-κB), and histological changes in joints. YCL showed anti-RA efficacy as it significantly reduced articular elastase, LPO and catalase level and ameliorates histological changes. This is in addition to its antioxidant efficacy as YCL shown a significant increase in GSH and SOD level. Also, YCL showed effective anti-inflammatory activity as it significantly decreased the expression of COX-2, TNF-α, and NF-ĸB. The therapeutic effect of YCL against RA was also evident from lower arthritis scoring and reduced hematological parameter (ESR, WBC, and C-reactive protein level). The abilities to inhibit proinflammatory cytokines and modulation of antioxidant states that the protective effect of YCL on arthritis rats might be mediated via the modulation of the immune system. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 619-629, 2017.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ioimbina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Catalase/metabolismo , Colágeno Tipo II , Ciclo-Oxigenase 2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Glutationa/metabolismo , Peroxidação de Lipídeos , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Ioimbina/uso terapêutico
10.
Microb Pathog ; 101: 76-82, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27836761

RESUMO

Increasing occurrence of gastroenteritis outbreaks caused by food borne opportunistic microorganisms has become a major problem in food industry as well as in immunocompromised host. Antimicrobial agents are losing their efficacy due to increase in the microbial resistance. For such reasons, conventional treatment has become limited to manage the infections state. Need of the hour is to instigate the search for safer holistic alternatives. The present study was hence conducted to assess the antibiofilm effect and mode of action of aquo alcoholic extracts of Holarrhena antidysentrica (Ha) and Andrographis paniculata (Ap) against the Salmonella enterica serovar typhimurium. Both the extracts were screened for the presence of phytocompounds followed by the characterization using Attenuated Total Reflection (ATR) infrared spectroscopy and bioactivity finger print analysis. Anti-biofilm assays were determined to test the potential of both extracts to inhibit the biofilm formation, while Propidium Iodide (PI) uptake analysis revealed that cell membrane was damaged by the exposure of nutraceuticals for 1 h. This study has demonstrated that both nutraceuticals have anti-biofilm and antimicrobial activity perturbing the membrane integrity of food-borne S. typhimurium and could be used as curative remedy to control the food borne microbial infection.


Assuntos
Andrographis/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Holarrhena/química , Extratos Vegetais/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Biofilmes/crescimento & desenvolvimento , Membrana Celular/fisiologia , Permeabilidade/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Propídio/análise , Salmonella typhimurium/fisiologia , Análise Espectral , Coloração e Rotulagem
12.
Metab Brain Dis ; 31(2): 299-309, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26477945

RESUMO

Reactivity to myelin associated proteins is the hallmark of human multiple sclerosis (M.S) and its experimental counterparts. However, the nature of such reactivity has not been described fully. Herein, we report that myelin basic protein (MBP) reactivity accumulates in a rat model for M.S. over a period of time and sensitizes TRAIL mediated progressive oligodendrocyte apoptosis. We used active immunization by Myelin Oligodendrocyte Glycoprotein (MOG, 50 µg) to study chronic remitting relapsing encephalomyelitis in rats. A time point analysis of the progressive disease revealed cumulative accumulation of anti myelin basic protein antibodies during the disease progression with minimal change in the anti-MOG antibodies. Increased reactivity to MBP was studied to sensitize TNF related apoptosis-inducing ligand (TRAIL) and other proinflammatory cytokines in a cumulative fashion leading to the Caspase dependent apoptosis of oligodendrocytes and myelin loss. In a rescue experiment, we could limit the demyelination and prevent disease progression by neutralizing the effector, TRAIL in an early stage of the disease. This is the first study to identify the accumulation of MBP antibodies in MOG induced EAE which possibly leads to TRAIL sensitized oligodendrocyte apoptosis in the white mater of EAE rats. This finding stresses on the need to study MBP antibody titers in M.S. patients and therefore might serve as an alternate marker for progressive demyelination.


Assuntos
Apoptose/fisiologia , Esclerose Múltipla/metabolismo , Proteína Básica da Mielina/metabolismo , Oligodendroglia/citologia , Substância Branca/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Masculino , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/metabolismo , Ratos Wistar , Medula Espinal/metabolismo
13.
J Pak Med Assoc ; 66(7): 884-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27427141

RESUMO

Infections due to Dengue virus are widespread throughout the world. Disease starts with mild flu like sickness to a severe intricate condition which results in the death of the patient. Dengue illness has high morbidity and mortality in Pakistan as well as in other Asian countries. The Review article is a discourse analysis that explores the facts about the history, emergence and impact of dengue in Pakistan and other Asian countries. Data was collected from internet sources, mainly using Science Direct and PubMed. The final literature was reviewed and summarised. About 150 articles were identified and 47 articles were shortlisted for final review. Aedesaegypti was found to be a major vector for the transmission and spread of dengue illness. Treatment comprises supportive therapy as no specific treatment was available. During the last couple of years, the incidence of dengue fever was extraordinary in metropolitan cities of Pakistan.


Assuntos
Controle de Doenças Transmissíveis , Vírus da Dengue , Dengue , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Dengue/diagnóstico , Dengue/epidemiologia , Dengue/terapia , Dengue/virologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/fisiologia , Saúde Global , Humanos , Incidência
14.
Int J Surg Case Rep ; 115: 109279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38245947

RESUMO

INTRODUCTION AND IMPORTANCE: Although IUD has become more popular in recent years, its migration through uterine perforation is a rare but serious complication. PRESENTATION OF CASE: We present the case of a young otherwise healthy woman with a missing IUD that had penetrated terminal ileum. CLINICAL DISCUSSION: The incidence of uterine perforation after IUD insertion has been reported 1.3 to 1.6 per 1000 insertions. Although a rare complication, it can cause serious problems requiring major surgery. CONCLUSION: Uterine perforation and migration of IUD is a rare but serious complication that should be considered in all missing IUD threads.

15.
PLoS One ; 19(8): e0307512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39093838

RESUMO

The multifunctional autoprocessing repeat-in-toxin (MARTX) toxin is the primary virulence factor of Vibrio vulnificus displaying cytotoxic and hemolytic properties. The cysteine protease domain (CPD) is responsible for activating the MARTX toxin by cleaving the toxin precursor and releasing the mature toxin fragments. To investigate the structural determinants for inositol hexakisphosphate (InsP6)-mediated activation of the CPD, we determined the crystal structures of unprocessed and ß-flap truncated MARTX CPDs of Vibrio vulnificus strain MO6-24/O in complex with InsP6 at 1.3 and 2.2Å resolution, respectively. The CPD displays a conserved domain with a central seven-stranded ß-sheet flanked by three α-helices. The scissile bond Leu3587-Ala3588 is bound in the catalytic site of the InsP6-loaded form of the Cys3727Ala mutant. InsP6 interacts with the conserved basic cleft and the ß-flap inducing the active conformation of catalytic residues. The ß-flap of the post-CPD is flexible in the InsP6-unbound state. The structure of the CPD Δß-flap showed an inactive conformation of the catalytic residues due to the absence of interaction between the active site and the ß-flap. This study confirms the InsP6-mediated activation of the MARTX CPDs in which InsP6-binding induces conformational changes of the catalytic residues and the ß-flap that holds the N terminus of the CPD in the active site, facilitating hydrolysis of the scissile bond.


Assuntos
Ácido Fítico , Vibrio vulnificus , Vibrio vulnificus/enzimologia , Vibrio vulnificus/genética , Vibrio vulnificus/metabolismo , Ácido Fítico/metabolismo , Domínio Catalítico , Cisteína Proteases/metabolismo , Cisteína Proteases/química , Cisteína Proteases/genética , Cristalografia por Raios X , Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Domínios Proteicos , Modelos Moleculares , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Sequência de Aminoácidos
16.
Eur J Case Rep Intern Med ; 11(6): 004549, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846674

RESUMO

Introduction: Ventricular septal defect (VSD) is a severe complication following acute myocardial infarction (MI) resulting from mechanical disruption of the interventricular septum due to extensive myocardial necrosis. Despite advances in management, the mortality rate approaches 50%. We report a case of a 58-year-old male with VSD following MI who was successfully treated with a delayed surgical approach after haemodynamic support using Impella. Case description: A 58-year-old man with type 2 diabetes mellitus and hypertension presented with three days of chest pain. Testing revealed late presenting acute anterior ischaemic infarction and left-to-right shunt in the apical ventricular septum. Urgent cardiac catheterisation showed near-total occlusion of the left anterior descending artery. An Impella CP® was placed before angioplasty with a drug-eluting stent to optimise haemodynamics. After a multidisciplinary discussion, the Impella CP® was upgraded to Impella 5.5®, and surgery was delayed allowing for scar formation. The patient remained in the intensive care unit, where he underwent physical therapy, showing improvements in exercise tolerance by the time of surgery. He underwent a left ventriculotomy with a successful repair via an endocardial patch 28 days after initial presentation. Post-operative recovery was uneventful, with the patient discharged five days later, reporting no physical limitations one month post-discharge. Conclusion: The successful management of VSD post-MI relies on interdisciplinary collaboration, careful timing of surgical intervention and the strategic use of mechanical support devices such as the Impella. This case highlights the potential for favourable outcomes when tailored treatment approaches are employed. LEARNING POINTS: Given the rarity of ventricular septal defects (VSD) post-myocardial infarction (MI), maintaining a high index of suspicion, particularly in patients with anterior infarcts and other high-risk features, is imperative for ensuring early recognition and management of this life-threatening complication.Surgical repair is the treatment of choice for VSD post-MI, offering improved survival rates, particularly when intervention is delayed to allow for myocardial scarring.Mechanical circulatory support devices, such as the Impella, can play a crucial role in bridging patients to surgical repair by providing temporary haemodynamic stabilisation. However, timing is vital, and early initiation of mechanical support can prevent the progression of cardiogenic shock and multi-organ failure.

17.
ACS Omega ; 9(30): 32745-32759, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100302

RESUMO

The release of palladium nanoparticles (PdNPs) from autocatalytic converters has raised concerns regarding public health and the environment due to their emergence as anthropogenic contaminants. With growing vehicular population, there is an urgent need for comprehensive toxicological studies of PdNPs to mitigate their risk. The present study aims to investigate the effects of spherical PdNPs with average sizes of 20 and 80 nm, as well as Pd nanorods, on the lung function of female Wistar rats following oral exposure to environmentally relevant doses (1 and 10 µg/kg) over a period of 28 days. Various biological parameters were evaluated, including liver and kidney biochemical changes, lung oxidative stress markers (SOD, CAT, GSH, LPO), lung inflammatory markers (IL-1ß, IL-8, IL-6, and TNF-α), and histopathological alterations in the lungs. Additionally, the potential mitigating effects of naringin on PdNPs-induced toxicity were examined. The results demonstrate a significant increase in oxidative stress, the onset of inflammation, and histological changes in lung alveolar sacs upon exposure to all tested particles. Specifically, 20@PdNPs and PdNRs exhibited higher cytotoxicity and pro-inflammatory properties compared to 80@PdNPs. Naringin effectively attenuated the pulmonary toxicity induced by PdNPs by modulating oxidative and inflammatory pathways. These findings contribute to the sustainable development of PdNPs for their future applications in the biomedical and environmental sectors, ensuring the advancement of safe and sustainable nanotechnology.

18.
Mol Biol Cell ; 35(7): ar93, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656801

RESUMO

Wnt signaling is a crucial developmental pathway involved in early development as well as stem-cell maintenance in adults and its misregulation leads to numerous diseases. Thus, understanding the regulation of this pathway becomes vitally important. Axin2 and Nkd1 are widely utilized negative feedback regulators in Wnt signaling where Axin2 functions to destabilize cytoplasmic ß-catenin, and Nkd1 functions to inhibit the nuclear localization of ß-catenin. Here, we set out to further understand how Axin2 and Nkd1 regulate Wnt signaling by creating axin2gh1/gh1, nkd1gh2/gh2 single mutants and axin2gh1/gh1;nkd1gh2/gh2 double mutant zebrafish using sgRNA/Cas9. All three Wnt regulator mutants were viable and had impaired heart looping, neuromast migration defects, and behavior abnormalities in common, but there were no signs of synergy in the axin2gh1/gh1;nkd1gh2/gh2 double mutants. Further, Wnt target gene expression by qRT-PCR and RNA-seq, and protein expression by mass spectrometry demonstrated that the double axin2gh1/gh1;nkd1gh2/gh2 mutant resembled the nkd1gh2/gh2 phenotype demonstrating that Nkd1 functions downstream of Axin2. In support of this, the data further demonstrates that Axin2 uniquely alters the properties of ß-catenin-dependent transcription having novel readouts of Wnt activity compared with nkd1gh2/gh2 or the axin2gh1/gh1;nkd1gh2/gh2 double mutant. We also investigated the sensitivity of the Wnt regulator mutants to exacerbated Wnt signaling, where the single mutants displayed characteristic heightened Wnt sensitivity, resulting in an eyeless phenotype. Surprisingly, this phenotype was rescued in the double mutant, where we speculate that cross-talk between Wnt/ß-catenin and Wnt/Planar Cell Polarity pathways could lead to altered Wnt signaling in some scenarios. Collectively, the data emphasizes both the commonality and the complexity in the feedback regulation of Wnt signaling.


Assuntos
Proteína Axina , Via de Sinalização Wnt , Proteínas de Peixe-Zebra , Peixe-Zebra , beta Catenina , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteína Axina/metabolismo , Proteína Axina/genética , beta Catenina/metabolismo , Proteínas de Transporte , Mutação/genética , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
19.
J Biomol Struct Dyn ; : 1-11, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294714

RESUMO

Inhibitors of α-glucosidase have been used to treat type-2 diabetes (T2DM) by preventing the breakdown of carbohydrates into glucose and prevent enhancing glucose conversion. Structure-based virtual screening (SBVS) was used to generate novel chemical scaffold-ligand α-glucosidase inhibitors. The databases were screened against the receptor α-glucosidase using SBVS and molecular dynamics simulation (MDS) techniques in this study. Based on molecular docking studies, three and two compounds of α-glucosidase inhibitors were chosen from a commercial database (ZINC) and an In-house database for this study respectively. The mode of binding interactions of the selected compounds later predicted their α-glucosidase inhibitory potential. Finally, one out of three lead compound from ZINC and one out of two lead compound from In-house database were shortlisted based on interactions. Furthermore, MDS and post-MDS strategies were used to refine and validate the shortlisted leads along with the reference acarbose/α-glucosidase. The Hits' ability to inhibit α-glucosidase was predicted by SBVS, indicating that these compounds have good inhibitory activities. The lead inhibitor's structure may serve as templates for the design of novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is necessary. These insights can help rationally design new effective anti-diabetic drugs.Communicated by Ramaswamy H. Sarma.

20.
Heliyon ; 10(2): e24165, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38293496

RESUMO

Carrot is a seasonal perishable tuberous root vegetable which presents a preservation challenge owing to its elevated moisture content. Recently, carrot processing has received more attention because of its many health-promoting qualities and the reduction of postharvest losses in a cost-effective safe way. This study was designed to sort out the effective solar drying technique including pre-treatment that would retain the color and quality characteristics of dehydrated carrot. Carrot slices were subjected to dry using open sun drying (D1), solar drying long chimney (D2), solar drying short chimney (D3) and box solar drying (D4) techniques with the pretreatments of ascorbic acid 1 % (C3), citric acid 5 % (C4), potassium metabisulfite 1 % (C5) and potassium sodium tartrate 0.3 % (C6) before drying. Drying characteristics, nutritional attributes, phytochemicals and antioxidant of the dehydrated carrot samples were compared with the fresh sample and untreated (control) sample. Results showed that D4 was a good drying method to preserve nutritional quality with good appearance. Among the pretreatments, C5 and C4 resulted improved nutritional quality retention, enhanced visual acceptability and enriched antioxidant activities. PCA (Principal Component Analysis) and correlation matrix revealed that D4 with C5 retained the maximum amount of vitamin, minerals, total phenolic content, antioxidant and admirable dehydrated carrot color by inactivating enzymatic reaction. Therefore, box solar drying with potassium metabisulfite pretreatment would be very promising for functional carrot drying retaining acceptable color and nutrition composition.

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