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1.
Environ Res ; 249: 118463, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38342201

RESUMEN

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.


Asunto(s)
Redes Neurales de la Computación , Termogravimetría , Termogravimetría/métodos , Termodinámica , Cinética , Modelos Químicos
2.
Pediatr Surg Int ; 40(1): 171, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958763

RESUMEN

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.


Asunto(s)
Músculos Abdominales , Pared Abdominal , Hernias Diafragmáticas Congénitas , Debilidad Muscular , Colgajos Quirúrgicos , Humanos , Hernias Diafragmáticas Congénitas/cirugía , Hernias Diafragmáticas Congénitas/complicaciones , Recién Nacido , Estudios Retrospectivos , Masculino , Femenino , Pared Abdominal/cirugía , Debilidad Muscular/etiología , Debilidad Muscular/cirugía , Músculos Abdominales/cirugía , Herniorrafia/métodos , Complicaciones Posoperatorias/cirugía , Resultado del Tratamiento
3.
Funct Integr Genomics ; 23(2): 186, 2023 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-37243790

RESUMEN

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.


Asunto(s)
Osteoporosis , Humanos , Anciano , Células Cultivadas , Osteoporosis/genética , Quimiocinas/genética , Receptores de Quimiocina/genética , Análisis de Secuencia de ARN
4.
J Biochem Mol Toxicol ; 36(11): e23187, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35920545

RESUMEN

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.


Asunto(s)
Diosmina , Neoplasias Pulmonares , Masculino , Ratones , Animales , Benzo(a)pireno/toxicidad , Diosmina/efectos adversos , Diosmina/metabolismo , Antígeno Carcinoembrionario/metabolismo , Antioxidantes/farmacología , Dinoprostona/metabolismo , Pulmón/metabolismo , Carcinogénesis , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/metabolismo , Ciclooxigenasa 2/metabolismo
5.
Environ Toxicol ; 37(9): 2153-2166, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35567572

RESUMEN

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.


Asunto(s)
Neoplasias del Colon , Hesperidina , Estrés Oxidativo , 1,2-Dimetilhidrazina/toxicidad , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Colon/metabolismo , Neoplasias del Colon/patología , Glutatión/metabolismo , Hesperidina/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Mucinas/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
6.
J Pak Med Assoc ; 72(5): 878-881, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35713048

RESUMEN

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.


Asunto(s)
Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Adolescente , Adulto , Estudios Transversales , Humanos , Masculino , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Profesionales/epidemiología , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
7.
Public Health Nutr ; 24(7): 1619-1628, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33494852

RESUMEN

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.


Asunto(s)
COVID-19 , Control de Enfermedades Transmisibles/estadística & datos numéricos , Composición Familiar , Inseguridad Alimentaria , Poblaciones Vulnerables/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Irán , Análisis de Clases Latentes , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Encuestas y Cuestionarios
8.
Environ Toxicol ; 32(2): 619-629, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27028940

RESUMEN

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.


Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Yohimbina/farmacología , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Artritis Experimental/inmunología , Artritis Experimental/metabolismo , Artritis Reumatoide/metabolismo , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Catalasa/metabolismo , Colágeno Tipo II , Ciclooxigenasa 2/metabolismo , Evaluación Preclínica de Medicamentos , Femenino , Glutatión/metabolismo , Peroxidación de Lípido , FN-kappa B/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo , Yohimbina/uso terapéutico
9.
Microb Pathog ; 101: 76-82, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27836761

RESUMEN

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.


Asunto(s)
Andrographis/química , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Holarrhena/química , Extractos Vegetales/farmacología , Salmonella typhimurium/efectos de los fármacos , Antibacterianos/aislamiento & purificación , Biopelículas/crecimiento & desarrollo , Membrana Celular/fisiología , Permeabilidad/efectos de los fármacos , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/aislamiento & purificación , Propidio/análisis , Salmonella typhimurium/fisiología , Análisis Espectral , Coloración y Etiquetado
11.
Metab Brain Dis ; 31(2): 299-309, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26477945

RESUMEN

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.


Asunto(s)
Apoptosis/fisiología , Esclerosis Múltiple/metabolismo , Proteína Básica de Mielina/metabolismo , Oligodendroglía/citología , Sustancia Blanca/metabolismo , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Masculino , Esclerosis Múltiple/inmunología , Glicoproteína Mielina-Oligodendrócito/metabolismo , Ratas Wistar , Médula Espinal/metabolismo
12.
J Pak Med Assoc ; 66(7): 884-8, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27427141

RESUMEN

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.


Asunto(s)
Control de Enfermedades Transmisibles , Virus del Dengue , Dengue , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/organización & administración , Dengue/diagnóstico , Dengue/epidemiología , Dengue/terapia , Dengue/virología , Virus del Dengue/efectos de los fármacos , Virus del Dengue/fisiología , Salud Global , Humanos , Incidencia
13.
Int J Surg Case Rep ; 115: 109279, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38245947

RESUMEN

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.

14.
Eur J Case Rep Intern Med ; 11(6): 004549, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846674

RESUMEN

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.

15.
J Biomol Struct Dyn ; : 1-11, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294714

RESUMEN

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.

16.
Mol Biol Cell ; 35(7): ar93, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38656801

RESUMEN

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.


Asunto(s)
Proteína Axina , Vía de Señalización Wnt , Proteínas de Pez Cebra , Pez Cebra , beta Catenina , Animales , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteína Axina/metabolismo , Proteína Axina/genética , beta Catenina/metabolismo , Proteínas Portadoras , Mutación/genética , Proteínas de Pez Cebra/metabolismo , Proteínas de Pez Cebra/genética
17.
Heliyon ; 10(2): e24165, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38293496

RESUMEN

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.

18.
J Mater Chem B ; 12(8): 2158-2179, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38323437

RESUMEN

The repair of mandibular defects is a challenging clinical problem, and associated infections often hinder the treatment, leading to failure in bone regeneration. Herein, a multifunctional platform is designed against the shortages of existing therapies for infected bone deficiency. 2D Ti3C2 MXene and berberine (BBR) are effectively loaded into 3D printing biphasic calcium phosphate (BCP) scaffolds. The prepared composite scaffolds take the feature of the excellent photothermal capacity of Ti3C2 as an antibacterial, mediating NIR-responsive BBR release under laser stimuli. Meanwhile, the sustained release of BBR enhances its antibacterial effect and further accelerates the bone healing process. Importantly, the integration of Ti3C2 improves the mechanical properties of the 3D scaffolds, which are beneficial for new bone formation. Their remarkable biomedical performances in vitro and in vivo present the outstanding antibacterial and osteogenic properties of the Ti3C2-BBR functionalized BCP scaffolds. The synergistic therapy makes it highly promising for repairing infected bone defects and provides insights into a wide range of applications of 2D nanosheets in biomedicine.


Asunto(s)
Berberina , Hidroxiapatitas , Nitritos , Andamios del Tejido , Elementos de Transición , Berberina/farmacología , Regeneración Ósea , Antibacterianos/farmacología , Impresión Tridimensional
19.
Cell Immunol ; 284(1-2): 51-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23921080

RESUMEN

OBJECTIVES: Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. METHODS: Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1ß, TNF-α, IL-10 and PGE2) and histological studies in joints. RESULTS: Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. CONCLUSIONS: In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.


Asunto(s)
Alcaloides/farmacología , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Benzodioxoles/farmacología , Piperidinas/farmacología , Alcamidas Poliinsaturadas/farmacología , Animales , Artritis Experimental/enzimología , Artritis Experimental/inmunología , Artritis Reumatoide/enzimología , Artritis Reumatoide/inmunología , Catalasa/análisis , Dinoprostona/análisis , Glutatión/análisis , Histocitoquímica , Inflamación/tratamiento farmacológico , Inflamación/enzimología , Inflamación/inmunología , Interleucina-10/análisis , Interleucina-1beta/análisis , Masculino , Óxido Nítrico/análisis , Elastasa Pancreática/análisis , Peroxidasa/análisis , Distribución Aleatoria , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Factor de Necrosis Tumoral alfa/análisis
20.
Rheumatol Int ; 33(3): 657-63, 2013 03.
Artículo en Inglés | MEDLINE | ID: mdl-22527139

RESUMEN

Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation. In our study, rheumatoid arthritis was induced in Wistar rats by intradermal injections of 100 µl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail. Disease developed about 13 ± 1 days after immunization and treatment with hesperidin (HES) at a dose of 160 mg kg(-1) body weight was given after onset of disease daily until 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters and histological evaluations in joints. A steady increase in the articular elastase, nitric oxide and lipid peroxidation was observed in joints of arthritic rats as compared to control, whereas a significant decrease in reduced glutathione, superoxide dismutase activity and catalase was observed in collagen-induced arthritis rats as compared to control group. The results from the present work indicate that the treatment with hesperidin was effective in bringing about significant changes on all the parameters studied in collagen-induced arthritis rats. These data confirm that erosive destruction of the joint cartilage in collagen-induced arthritis is due free radicals released by activated neutrophils and produced by other biochemical pathways. In the present study, an attempt has been made to amelioration of the disease process by a natural product. These results suggest that oral administration of HES could be effective for treating human RA patients.


Asunto(s)
Artritis Experimental/tratamiento farmacológico , Radicales Libres/metabolismo , Hesperidina/farmacología , Activación Neutrófila/efectos de los fármacos , Infiltración Neutrófila/efectos de los fármacos , Animales , Artritis Experimental/inmunología , Artritis Experimental/metabolismo , Catalasa/metabolismo , Hesperidina/uso terapéutico , Masculino , Óxido Nítrico/análisis , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
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