The current study aimed to develop a topical emulgel of dasatinib (DTB) for rheumatoid arthritis (RA) treatment to reduce systemic side effects. The quality by design (QbD) approach was employed to ...optimize DTB-loaded nano-emulgel using a central composite design (CCD). Emulgel was prepared using the hot emulsification method, and then the particle size (PS) was reduced using the homogenization technique. The PS and % entrapment efficiency (% EE) were found to be 172.53 ± 3.33 nm (0.160 ± 0.014 PDI) and 95.11 ± 0.16%, respectively. The nano-emulsion (CF018 emulsion) in vitro drug release profile showed sustained release (SR) up to 24 h. MTT assay results from an in vitro cell line study revealed that formulation excipients had no effect, whereas emulgel showed a high degree of internalization. Furthermore, emulgel treatment significantly reduced LPS-induced TNF-α production in RAW 264.7 cells. The spherical shape was depicted in FESEM images of optimized nano-emulgel (CF018 emulgel) formulation. Ex vivo skin permeation was significantly increased when compared to the free drug-loaded gel (FDG). In vivo data revealed that the optimized CF018 emulgel is a non-irritant and is safe. In terms of paw swelling, the FCA-induced arthritis model demonstrated that the CF018 emulgel reduced paw swelling percentage compared to adjuvant-induced arthritis (AIA) control group. Following clinical testing in the near future, the designed preparation could be a viable alternative treatment for RA.
Numerous treatments are available for cancer, including chemotherapy, immunotherapy, radiation therapy, hormone therapy, biomarker testing, surgery, photodynamic therapy, etc. Photodynamic therapy ...(PDT) is an effective, non-invasive, novel, and clinically approved strategy to treat cancer. In PDT, three main agents are utilized, i.e., photosensitizer (PS) drug, oxygen, and light. At first, the photosensitizer is injected into blood circulation or applied topically, where it quickly becomes absorbed or accumulated at the tumor site passively or actively. Afterward, the tumor is irradiated with light which leads to the activation of the photosensitizing molecule. PS produces the reactive oxygen species (ROS), resulting in the death of the tumor cell. However, the effectiveness of PDT for tumor destruction is mainly dependent on the cellular uptake and water solubility of photosensitizer molecules. Therefore, the delivery of photosensitizer molecules to the tumor cell is essential in PDT against cancer. The non-specific distribution of photosensitizer results in unwanted side effects and unsuccessful therapeutic outcomes. Therefore, to improve PDT clinical outcomes, the current research is mostly focused on developing actively targeted photosensitizer molecules, which provide a high cellular uptake and high absorption capacity to the tumor site by overcoming the problem associated with conventional PDT. Therefore, this review aims to provide current knowledge on various types of actively and passively targeted organic and inorganic nanocarriers for different cancers.
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•Parkinson disease (PD) is characterized by a loss of dopaminergic neurones in the substantia nigra pars compacta.•Fibroblast growth factor 21 (FGF21) is a metabolic hormone recently ...identified as a potent neuroprotective agent.•Impairment of autophagy due to factors like ageing elevates accumulation of misfolded proteins contributing towards possible neurodegenerative pathology.•Autophagy dysfunction causes endoplasmic reticulum (ER) stress that may stimulate the Activating Transcription Factor 4 (ATF 4) which help in preserving neuronal survival and health.•ATF 4 regulates FGF21 expression during ER stress that may promotes neuroprotection in PD through FGF21 mediated mechanism (s).
Parkinson disease (PD) is the second common neurodegenerative disorder after Alzheimer’s disease (AD). The predominant pathological hallmark is progressive loss of dopaminergic (DA) neurones in the substantia nigra (SN) complicated by aggregation of misfolded forms of alpha-synuclein (α-syn). α-syn is a cytosolic synaptic protein localized in the presynaptic neuron under normal circumstances. What drives misfolding of this protein is largely unknown. However, recent studies suggest that autophagy might be an important risk factor for contributing towards PD. Autophagy is an evolutionarily conserved mechanism that causes the clearance or degradation of misfolded, mutated and damaged proteins, organelles etc. However, in an aging individual this process might deteriorate which could possibly lead to the accumulation of damaged proteins. Hence, autophagy modulation might provide some interesting cues for the treatment of PD. Additionally, Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective in various neurodegenerative conditions possibly via mediation of autophagy.
Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that affects mostly young women in which tissue-binding autoantibodies and immune complexes cause damage to organs and tissues. SLE is ...characterised by aberrant immunological responses that result in the release of higher levels and immunogenic nucleic acids, proteins, and other self-antigens. Autoimmune Haemolytic Anaemia (AIHA) is a condition in which antibodies against red blood cells are present. It is classified as a warm and cold antibody AIHA. The causes of warm antibody AIHA are autoimmune illnesses, infections, or even malignancy. The presence of Immunoglobulin G (IgG) antibodies can indicate warm autoimmune haemolytic anaemia (warm agglutinin anaemia), which is characterised by fatigue and other constitutional symptoms. Although, autoimmune haemolytic anaemia can be a component of the SLE spectrum, warm autoimmune haemolytic anaemia as the first manifestation of SLE is exceedingly rare. This case report describes a case of a 23-years-old female who presented to the hospital with complaints of breathlessness and chest pain. After evaluation she was found to have pericardial tamponade and AIHA. Pericardiocentesis was done and further investigations confirmed the diagnosis of SLE. She was treated with injectable methylprednisolone, injectable antibiotics, Tab. hydroxychloroquine, Tab. febuxostat ,Tab. colchicine, oral antidiuretic, oral levothyroxine and other supportive management. The lack of unambiguous pathognomonic characteristics or tests, coupled with the variable presentation of SLE, makes diagnosis tricky. Overall, AIHA can be an initial presentation as well as a part of other disease processes, emphasising the significance of a comprehensive work in patients with AIHA.
Chikungunya virus (CHIKV) is a reemerging alphavirus causing chikungunya disease (CHIKD) and is transmitted to humans by
mosquitoes. The virus establishes an intricate balance of cellular ...interactions that ultimately helps in its replication and dodges cellular immune response. In an attempt to identify cellular host factors required during CHIKV replication in Aag2 cells, we performed global transcriptomics of CHIKV-infected Aag2 cells, and further, we compared this library with the
RNAi Screening Center (DRSC) database and identified transcripts that were regulated in Aedes aegypti during CHIKV infection. These analyses revealed specific pathways, such as ubiquitin-related pathways, proteolysis pathways, protein catabolic processes, protein modification, and cellular protein metabolic processes, involved during replication of the virus. Loss-of-function assays of selected candidates revealed their proviral or antiviral characteristics upon CHIKV infection in A. aegypti-derived Aag2 cells. Further validations identified that the ubiquitin proteasomal pathway is required for CHIKV infection in A. aegypti and that an important member of this family of proteins, namely, AeCullin-3 (
ortholog of human cullin-3), is a proviral host factor of CHIKV replication in Aag2 cells.
Arboviruses cause several diseases in humans and livestock. Vector control is the main strategy for controlling diseases transmitted by mosquitoes. In this context, it becomes paramount to understand how the viruses replicate in the vector for designing better transmission blocking strategies. We obtained the global transcriptome signature of A. aegypti cells during CHIKV infection, and in order to obtain the maximum information from these data sets, we further utilized the well-characterized
system and arrived upon a set of transcripts and their pathways that affect A. aegypti cells during CHIKV infection. These analyses and further validations reveal that important pathways related to protein degradation are actively involved during CHIKV infection in A. aegypti and are mainly proviral. Targeting these molecules may provide novel approaches for blocking CHIKV replication in A. aegypti.
The purpose of the present study was to optimise diclofenac diethylamine-loaded liquid crystal nanoparticles (LCNPs) using the principles of quality by design. Based on risk assessment, the effect of ...various formulation variables on the critical quality attributes was investigated. A three-level Box-Behnken design with 14 runs was utilised for optimisation. The LCNPs were evaluated for size, polydispersity index, zeta potential, entrapment efficiency, morphology, solid-state characterisation, and drug release. The LCNPs were found to show prolonged drug release up to 12 h as compared to the free drug which showed a 100% release in less than 3 h. The optimised formulation was further investigated for scale-up studies, incorporated into carbopol gel and characterised for rheological parameters, skin permeation, and skin accumulation. Ex-vivo skin permeation studies revealed 1.55 times more permeation as compared to the marketed formulation. The designed gel had the potential to prolong the drug release, improve the permeation of drug through the skin layers, and industrial feasibility.
Small heat shock protein B1 (HspB1) has been reported to play an essential role in thermotolerance. This study aimed to determine a correlation (if any) between HspB1 expression and age at first egg ...lay (puberty) in a native cross‐layer poultry of Punjab under heat stress. Forty native cross‐layer birds were reared in two different seasons, viz. summer (THI was more than 27), classified as the heat‐stressed group (n = 20) and winter season (THI was less than 21), classified as the control group (n = 20). Blood was collected from both the groups of birds in their 15th week of age and at puberty. Serum catalase and superoxide dismutase activities, reduced glutathione and corticosterone concentration and lipid peroxidation were measured to assess the oxidative stress in both the groups of birds. The serum antioxidants significantly decreased whilst corticosterone levels and lipid peroxidation significantly elevated in birds in response to summer heat stress. Moreover, in summer season, the activities of the antioxidant enzymes further decreased and lipid peroxidation further increased significantly in birds from their pre‐pubertal stage to puberty, which was not observed during the winter season. A clone of chicken HspB1 in BL21 (DE3) cells was revived, and recombinant HspB1 was purified using Ni‐NTA agarose column. Serum HspB1 concentration was estimated in different groups of birds by indirect ELISA that has been standardized using the recombinant chicken HspB1. Compared to the control, birds under heat stress had significantly higher serum HspB1 levels. The delay in puberty of all the heat‐stressed birds was significantly associated with the increase in their serum HspB1 levels. Taken together, the expression of HspB1 was found to be associated with age at puberty in the native cross poultry layers of Punjab.
Molecular characterization of Kinnow mutants KUMAR, SUNIL; AWASTHI, O P; BHARADWAJ, C ...
The Indian journal of agricultural sciences,
10/2022, Letnik:
91, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The present experiment was conducted during 2016-18 at Division of Fruits and Horticultural Technology, ICARIARI, New Delhi. A total of 40 Kinnow mutants and 1 wild type were selected for molecular ...characterization and diversity analyses. Thirty-four SSR markers were screened for polymorphism, of which only 2 were found informative. Twelve alleles were detected among 2 SSRs with an average of 6 alleles per locus and the highest number of alleles (7) was recorded in SSR locus AMB2. The average diversity indices of SSR, viz. allele frequency, gene diversity, observed heterozygosity and PIC were 0.415, 0.672, 0.415 and 0.611 respectively. The N-J tree was constructed based on the 2 SSRs data which clustered the mutants into 2 major groups. Subsequently, clusters were simplified into 6 clades which distinguished gamma-irradiated and EMS derived mutants and results were reconfirmed through principal coordinate analysis (PCoA). First three axes of PCoA contributed 80.88% of the cumulative variation among the Kinnow mutants. The analysis of molecular variance (AMOVA) explained 42% variation among the populations, 48 and 10% variation within and among the individuals respectively. The present investigation genetically characterized the Kinnow mutants and deciphered the genetic diversity among them. Thus, the variability generated through induced mutagenesis could be used as valuable genetic material for Kinnow improvement.
Abstract Background Primary percutaneous coronary intervention (PCI) is the current standard of care for acute ST elevation myocardial infarction (STEMI). Most of the data on primary PCI in acute ...STEMI is from western countries. We studied the outcomes of primary PCI for acute STEMI at a tertiary care center in North India. Methods Consecutive patients undergoing primary PCI for STEMI were prospectively studied during the period from February 2103 to May 2015. The outcomes assessed were all cause in hospital mortality, factors associated with mortality, major adverse cardiac and cerebrovascular event rate (composite of all cause in hospital mortality, non-fatal re infarction and stroke) and procedural complications. Results 371 patients underwent primary PCI during the study period. The mean age was 54 years and 82.7% were males. The mean total ischemia time and door to balloon times were 6.8 h and 51 min respectively. 96.4% patients underwent successful primary PCI. The total in hospital mortality was 12.9%. Mortality with cardiogenic shock at presentation was 66.7% while non-shock mortality was 2.6%. In hospital MACCE rate was 13.5%. Factors significantly associated with mortality were KILLIP class (OR: 8.4), door to balloon time (OR 1.02), final TIMI flow (OR 0.44) and severe LV dysfunction (OR 22.0). Procedure related adverse events were rare and there was no non-CABG associated major TIMI bleeding. Conclusion Primary PCI for acute STEMI is feasible in our setup and associated with high success rate, low mortality in non-shock patients and low complication rates.
Background: Effective attenuation of the sympathetic surge due to laryngoscopy and endotracheal intubation is needed. We wanted to compare the role of oral gabapentin (600 mg) and oral pregabalin ...(150 mg) in controlling this sympathetic surge.
Aims and Objectives: To compare the role of oral gabapentin (600 mg) and oral pregabalin (150 mg) as premedications for attenuating hemodynamic surge to laryngoscopy and endotracheal intubation.
Materials and Methods: 90 patients aged 18–45 years with ASA grade I or II posted for elective surgical procedure under general anesthesia were randomly allocated to two equal groups (45 in each group) to receive either 600 mg oral gabapentin or 150 mg oral pregabalin 1 h prior to surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and rate pressure product (RPP) were recorded after intubation at 1 (T1), 3 (T3), 5 (T5), and 10 (T10) min. Post-operative sedation and post-operative nausea and vomiting (PONV) were recorded and compared.
Results: Gabapentin attenuates hemodynamic surge in terms of HR, SBP, DBP, MAP, and RPP better than pregabalin during laryngoscopy and endotracheal intubation at 3, 5, and 10 min after intubation, while there was no significant difference between the two groups at 1 min after intubation. Post-operative sedation score and adverse effects like PONV and SpO2 fluctuations at different points in time were comparable.
Conclusion: Oral gabapentin (600 mg) was found to be more effective than oral pregabalin (150 mg) in attenuating the hemodynamic surge to laryngoscopy and intubation.
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