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1.
eNeuro ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937107

ABSTRACT

γ-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain which mediates its rapid effects on neuronal excitability via ionotropic GABAA receptors. GABA levels in the brain are critically dependent upon GABA-aminotransferase (GABA-AT) which promotes its degradation. Vigabatrin, a low affinity GABA-AT inhibitor, exhibits anticonvulsant efficacy but its use is limited due to cumulative ocular toxicity. OV329 is a rationally designed, next-generation GABA-AT inhibitor with enhanced potency. We demonstrate that sustained exposure to OV329 in mice reduces GABA-AT activity and subsequently elevates GABA levels in the brain. Parallel increases in the efficacy of GABAergic inhibition were evident, together with elevations in EEG delta power. Consistent with this, OV329 exposure reduced the severity of status epilepticus and the development of benzodiazepine refractory seizures. Thus, OV329 may be of utility in treating seizure disorders and associated pathologies that result from neuronal hyperexcitability.Significance Statement Enhancing inhibitory control over neurons to reduce excitability is a common strategy in treating seizure disorders. Here, we describe a novel compound, OV329, which acts on a common pathway to vigabatrin to increase inhibitory signaling following a low repeated dose paradigm. In vivo application of OV329 exhibited enhanced tonic GABA signaling in mice at the synaptic level in the hippocampus, and at the network level reduced seizure severity and the development of benzodiazepine refractory seizures. This suggests OV329 may be of clinical use in the treatment of seizure disorders.

2.
Endocrine ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878192

ABSTRACT

BACKGROUND: Severe symptomatic hyponatraemia is potentially life-threatening and hypertonic saline (HTS) is effective at rapidly correcting serum sodium. Several clinical guidelines have aimed to standardise the administration of HTS. However, evidence supporting the guidelines is limited, and concerns have been raised regarding the potential for overcorrection. OBJECTIVE: To assess the practices and perceptions surrounding HTS use in severe symptomatic hyponatraemia among United Kingdom (UK) endocrinologists and trainees. METHODS: An anonymous online survey was disseminated to Society for Endocrinology (UK) clinical members between 24/10/2023 and 30/11/2023 using a web-based multiple-choice questionnaire. RESULTS: We received 133 responses with a survey response rate of 8.3% (60.1% consultants, 33.1% trainees, 6.8% others). 85% of respondents employed bolus treatment with HTS only, with 9.8% using both bolus and continuous infusions. Most (53.2%) preferred 150 mL boluses, followed by 100 mL boluses (19.8%), while 5.5% of respondents used weight-based dosage. Commonly used HTS strengths were 2.7% (45.1%), followed by 1.8% (31.6%), while the 3% HTS strength recommended in guidelines was used by 21.8%. Contrary to guidelines, 78.6% did not administer a second bolus without waiting for the sodium result after the first bolus. Moreover, 86% have experience using venous blood gas sodium readings for monitoring. Overcorrection targets defined by 10 and 8 mmol/24 h cut-offs were used by 48.9% and 39.9%, respectively. For definite or anticipated overcorrection, 75.9% preferred 5% dextrose, while 40.6% had experience with desmopressin. CONCLUSION: Significant variation exists in HTS use for severe symptomatic hyponatraemia in the UK. Most clinicians prefer a more cautious approach in administering HTS. These data offer insight into real-life care and call for future research.

3.
Food Sci Nutr ; 12(6): 3787-3805, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38873476

ABSTRACT

This review covers the significance of green banana resistant starch (RS), a substantial polysaccharide. The food industry has taken an interest in green banana flour due to its 30% availability of resistant starch and its approximately 70% starch content on a dry basis, making its use suitable for food formulations where starch serves as the base. A variety of processing techniques, such as heat-moisture, autoclaving, microwaving, high hydrostatic pressure, extrusion, ultrasound, acid hydrolysis, and enzymatic debranching treatments, have made significant advancements in the preparation of resistant starch. These advancements aim to change the structure, techno-functionality, and subsequently the physiological functions of the resistant starch. Green bananas make up the highest RS as compared to other foods and cereals. Many food processing industries and cuisines now have a positive awareness due to the functional characteristics of green bananas, such as their pasting, thermal, gelatinization, foaming, and textural characteristics. It is also found useful for controlling the rates of cancer, obesity, and diabetic disorders. Moreover, the use of GBRS as prebiotics and probiotics might be significantly proved good for gut health. This study aimed at the awareness of the composition, extraction and application of the green banana resistant starch in the future food products.

4.
Commun Biol ; 7(1): 732, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886572

ABSTRACT

Ferroptosis is a unique iron-dependent form of non-apoptotic cell death characterized by devastating lipid peroxidation. Whilst growing evidence suggests that ferroptosis is a type of autophagy-dependent cell death, the underlying molecular mechanisms regulating ferroptosis are largely unknown. In this study, through an unbiased RNA-sequencing screening, we demonstrate the activation of a multi-faceted tumor-suppressor protein Par-4/PAWR during ferroptosis. Functional studies reveal that genetic depletion of Par-4 effectively blocks ferroptosis, whereas Par-4 overexpression sensitizes cells to undergo ferroptosis. More importantly, we have determined that Par-4-triggered ferroptosis is mechanistically driven by the autophagic machinery. Upregulation of Par-4 promotes activation of ferritinophagy (autophagic degradation of ferritin) via the nuclear receptor co-activator 4 (NCOA4), resulting in excessive release of free labile iron and, hence, enhanced lipid peroxidation and ferroptosis. Inhibition of Par-4 dramatically suppresses the NCOA4-mediated ferritinophagy signaling axis. Our results also establish that Par-4 activation positively correlates with reactive oxygen species (ROS) production, which is critical for ferritinophagy-mediated ferroptosis. Furthermore, Par-4 knockdown effectively blocked ferroptosis-mediated tumor suppression in the mouse xenograft models. Collectively, these findings reveal that Par-4 has a crucial role in ferroptosis, which could be further exploited for cancer therapy.


Subject(s)
Autophagy , Ferroptosis , Nuclear Receptor Coactivators , Reactive Oxygen Species , Ferroptosis/genetics , Humans , Animals , Nuclear Receptor Coactivators/metabolism , Nuclear Receptor Coactivators/genetics , Mice , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Lipid Peroxidation , Iron/metabolism , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Signal Transduction
5.
Pharm Res ; 41(6): 1183-1199, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38849712

ABSTRACT

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.


Subject(s)
Administration, Cutaneous , Anti-Inflammatory Agents , Dexamethasone , Drug Delivery Systems , Edema , Iontophoresis , Needles , Skin Absorption , Skin , Animals , Iontophoresis/methods , Dexamethasone/administration & dosage , Dexamethasone/pharmacokinetics , Dexamethasone/analogs & derivatives , Rats , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Edema/drug therapy , Drug Delivery Systems/methods , Skin/metabolism , Skin/drug effects , Male , Drug Liberation , Inflammation/drug therapy , Rats, Sprague-Dawley
6.
Front Genet ; 15: 1361610, 2024.
Article in English | MEDLINE | ID: mdl-38826807

ABSTRACT

Shigella dysenteriae has been recognized as the second most prevalent pathogen associated with diarrhea that contains blood, contributing to 12.9% of reported cases, and it is additionally responsible for approximately 200,000 deaths each year. Currently, there is no S. dysenteriae licensed vaccine. Multidrug resistance in all Shigella spp. is a growing concern. Current vaccines, such as O-polysaccharide (OPS) conjugates, are in clinical trials but are ineffective in children but protective in adults. Thus, innovative treatments and vaccines are needed to combat antibiotic resistance. In this study, we used immuno-informatics to design a new multiepitope vaccine and identified S. dysenteriae strain SD197's membrane protein targets using in-silico methods. The target protein was prioritized using membrane protein topology analysis to find membrane proteins. B and T-cell epitopes were predicted for vaccine formulation. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, a total of 8 B-cell epitopes, 12 MHC Class I epitopes, and 7 MHC Class II epitopes were identified for the Lipopolysaccharide export system permease protein LptF. Additionally, 17 MHC Class I epitopes and 14 MHC Class II epitopes were predicted for the Lipoprotein-releasing ABC transporter permease subunit LolE. These epitopes were selected and linked via KK, AAY, and GGGS linkers, respectively. To enhance the immunogenic response, RGD (arginine-glycine-aspartate) adjuvant was incorporated into the final vaccine construct. The refined vaccine structure exhibits a Ramachandran score of 91.5% and demonstrates stable interaction with TLR4. Normal Mode Analysis (NMA) reveals low eigenvalues (3.925996e-07), indicating steady and flexible molecular mobility of docked complexes. Codon optimization was carried out in an effective microbial expression system of the Escherichia coli K12 strain using the recombinant plasmid pET-28a (+). Finally, the entire in-silico analysis suggests that the suggested vaccine may induce a significant immune response against S. dysenteriae, making it a promising option for additional experimental trials.

8.
ACS Omega ; 9(24): 25730-25747, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38911743

ABSTRACT

New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.

9.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2601-2607, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38883477

ABSTRACT

Ossicular destruction is a common phenomenon in chronic otitis media due to an imbalance between osteoblasts and osteoclasts. Computed tomography helps us in the assessment of ossicular status, extent of pneumatization, and early identification of complications. This study aims to check the diagnostic accuracy of computed tomography temporal bone for the detection of ossicular erosion in comparison with the surgical findings taken as a gold standard. The use of this investigation as an adjunct can prove to be helpful in planning mastoid exploration as well as a primary reconstruction surgery especially in mucosal and early squamosal diseases. It's a cross-sectional validation study done on 50 patients with chronic otitis media (both mucosal and squamous type) from July 2022 to November 2023. Patients underwent CT scanning of temporal bone and ossicular status was reported by the radiologist. Later on, mastoid surgery was carried out and per operative findings were documented. 2 × 2 tables were formed and diagnostic accuracy of CT temporal bone was checked in terms of sensitivity, specificity, negative predictive value, and positive predictive value. The results revealed that CT temporal bone has a high diagnostic accuracy with a sensitivity of 92.5% and specificity of 100% for malleus (p value < 0.001). For incus and stapes, sensitivity came out to be 93.5% and 76% respectively and specificity values were 94.7% and 100% (p value < 0.001 for all) giving a verdict that the pre-operative use of this radiological investigation should be encouraged by otologists.

10.
Chemosphere ; 361: 142520, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38834092

ABSTRACT

Organic fertilizers have become a vector for the transport of microplastics (MPs), which pose human health concerns through the food chain. This study aimed to quantify and characterize MPs in eight different compost samples of various raw materials and their subsequent translocation to lettuce (Lacuta sativa) grown on contaminated composts. The results revealed that the MP abundance ranged from 3810 to 16530 MP/kg. Municipal solid waste compost (MSWC) had highest abundance (16082 ± 632 MP/kg), followed by leaf compost (LC) and organic compost (OC) (6299 ± 1011 and 3680 ± 419 MP/kg, respectively). MPs of <100 µm in size were most dominant in MSWC and LC. Fragments and fibers were the prevalent shape types, with white/transparent colored MPs being more abundant. Polyethylene (PE), polypropylene (PP) and polyethylene terephthalate (PET) were the dominant polymers. MPs accumulation in the lettuce leaves was greatest in the lettuce plants grown on MSWC, followed by those grown on LC and OC, indicating that MSWC grown lettuce is not suitable for human consumption. The decrease in the growth (leaf length, number of leaves, leaf fresh and weights) and physiological (membrane stability index, relative water contents) parameters of lettuce was in line with the trend of MP accumulations. Hence, it is highly important to regulate the plastic contents in compost because it is a threat to ecosystems and human health.


Subject(s)
Composting , Lactuca , Microplastics , Soil Pollutants , Microplastics/analysis , Lactuca/metabolism , Lactuca/growth & development , Lactuca/chemistry , Soil Pollutants/analysis , Soil Pollutants/metabolism , Soil/chemistry , Plant Leaves/metabolism , Plant Leaves/chemistry , Environmental Monitoring , Polymers/analysis , Solid Waste/analysis , Polyethylene , Fertilizers/analysis , Polypropylenes
11.
Diabet Med ; : e15340, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38741266

ABSTRACT

AIMS: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. METHODS: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. RESULTS: Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). CONCLUSIONS: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.

12.
Int J Biol Macromol ; 270(Pt 1): 132048, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38704062

ABSTRACT

Polysaccharides are favourable and promising biopolymers for wound care applications due to their abundant natural availability, low cost and excellent biocompatibility. They possess different functional groups, such as carboxylic, hydroxyl and amino, and can easily be modified to obtain the desirable properties and various forms. This review systematically analyses the recent progress in polysaccharides derived materials for wound care applications, emphasizing the most commonly used cellulose, chitosan, alginate, starch, dextran and hyaluronic acid derived materials. The distinctive attributes of each polysaccharide derived wound care material are discussed in detail, along with their different forms, i.e., films, membranes, sponges, nanoemulsions, nanofibers, scaffolds, nanocomposites and hydrogels. The processing methods to develop polysaccharides derived wound care materials are also summarized. In the end, challenges related to polysaccharides derived materials in wound care management are listed, and suggestions are given to expand their utilization in the future to compete with conventional wound healing materials.


Subject(s)
Biocompatible Materials , Polysaccharides , Wound Healing , Wound Healing/drug effects , Polysaccharides/chemistry , Polysaccharides/therapeutic use , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Animals , Hydrogels/chemistry , Hydrogels/therapeutic use , Bandages , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Chitosan/chemistry
13.
PLoS One ; 19(5): e0300418, 2024.
Article in English | MEDLINE | ID: mdl-38722921

ABSTRACT

The "Three Rural Issues", encompass challenges related to agriculture, farmer, and rural area, which hold significant importance in driving comprehensive rural revitalization efforts in China. Farmer entrepreneurship, as a crucial means to enhance productivity, create job opportunities, and increase residents' income, has gradually become a key driving force in promoting rural revitalization in the new stage of development in China. With the rapid development of rural e-commerce, farmer entrepreneurship has encountered new opportunities. This study utilizes the 2020 China Family Panel Studies (CFPS) data and employs a structural equation model (SEM) to analyze the direct impact of rural e-commerce participation on farmer entrepreneurial behavior, considering factors such as human capital, social capital, and network infrastructure. This study further explores the indirect effects and mechanisms of e-commerce participation as a mediating variable and analyzes the impact and mechanisms on agricultural entrepreneurship behavior. The findings are as follows: (1) E-commerce participation significantly promotes farmer entrepreneurial behavior; (2) E-commerce participation as a mediating variable has a positive indirect effect on the relationship between social trust, network infrastructure, human capital, and farmer entrepreneurial behavior; (3) E-commerce participation has a significant positive influence on farmer entrepreneurship in the agricultural sector, and farmers with higher levels of network infrastructure and human capital have a higher probability of choosing agricultural entrepreneurship under the influence of e-commerce participation. Finally, this study provides policy recommendations in terms of infrastructure construction, entrepreneurial policy environment, and education level, aiming to optimize the situation of farmer entrepreneurship and contribute to the comprehensive promotion of rural revitalization.Overall, the research in this paper effectively combines theory and empirical evidence to outline the direct and indirect impact mechanisms of rural e-commerce participation on farmers' entrepreneurial behavior and agriculture-related entrepreneurial behavior and to test the effects of their impacts. First, most of the existing literature deals with farmers in individual sample areas, while the sample selected in this paper is farmers in the whole country, which is relatively more generalizable; second, most of the previous studies explore the level of e-commerce in the inter-provincial or county areas, while this paper expands the empirical study of rural e-commerce on the entrepreneurial behavior of farmers and the micro-period of agricultural entrepreneurial behavior, and focuses on the impacts of the e-commerce activities of farmers on their entrepreneurial behavior.


Subject(s)
Agriculture , Entrepreneurship , Farmers , Rural Population , China , Farmers/psychology , Humans , Commerce , Social Capital
14.
ACS Omega ; 9(18): 19786-19795, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38737020

ABSTRACT

This study looked at using modified camelina oil to develop sustainable coatings that could replace those derived from petroleum-based materials for use in packaging and other industrial sectors. Solvent-free synthesis of maleic anhydride grafted camelina oil (MCO) was carried out at two different temperatures (200 and 230 °C) to obtain sustainable hydrophobic coating materials for paper substrates. Maleic anhydride grafting of camelina oil was confirmed with attenuated total reflectance-Fourier transform infrared and NMR spectroscopic techniques, and up to 16% grafting of maleic anhydride was achieved, as determined by the titration method. MCO, obtained at different reaction temperatures, was coated onto cellulosic paper and evaluated for its hydrophobicity, mechanical, oxygen, and water vapor barrier properties. Scanning electron microscopy indicated the homogeneous dispersion of coating material onto the paper substrate. MCO-coated papers (MCO-200C paper and MCO-230C paper) provided a water contact angle of above 90° which indicates that the modified oil was working as a hydrophobic coating. Water vapor permeability (WVP) testing of coated papers revealed a reduction in WVP of up to 94% in comparison to the uncoated paper. Moreover, an improved oxygen barrier property was also observed for paper coated with both types of MCO. Analysis of the mechanical properties showed a greater than 70% retention of tensile strength and up to a five-fold increase in elongation at break of coated versus uncoated papers. Overall, the results show that camelina oil, a renewable resource, can be modified to produce environmentally friendly hydrophobic coating materials with improved mechanical and water vapor barrier properties that can serve as a potential coating material in the packaging industry. The results of this research could find applications in the huge paper packaging industries, specially in food packaging.

15.
Med Oncol ; 41(6): 152, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743193

ABSTRACT

Metastasis is the most devastating attribute of breast cancer (BC) that leads to high mortality. It is a complex process of tumor cell migration, invasion, and angiogenesis. In this study, we evaluated the effect of ERA on BC metastasis and BC progression in vivo. The transwell invasion/migration and wound healing assays showed that ERA treatment significantly reduced the invasion and migration of BC cell lines. The expression of mesenchymal (E-cadherin and N-cadherin), matrix metalloproteinases (MMP2, MMP9), and stemness markers (Oct3) were down-regulated by ERA. Furthermore, ERA down-regulated angiogenic chemokines (CXCL1/2/3, CXCL5, and CXCL12) expression in the highly metastatic MDA-MB-231 cell line. The clonogenic survival of BC cells was also reduced by ERA treatment. Strikingly, ERA prevented DMBA-induced tumor growth in Swiss albino mice as depicted by a high animal survival rate (84%) in the ERA group and histopathological analysis. Conclusively, this study revealed that ERA possesses anti-metastatic potential and also reduces the growth of BC in vivo. Moreover, the GC-MS data revealed the presence of biologically active compounds (Lupeol, Phytol, phytosterol) and some rare (9, 19-Cyclolanost) phyto metabolites in ERA extract. However, further studies are suggestive to identify and isolate the therapeutic agents from ERA to combat BC and metastasis.


Subject(s)
Breast Neoplasms , Euphorbia , Plant Extracts , Animals , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Mice , Humans , Plant Extracts/pharmacology , Euphorbia/chemistry , Cell Line, Tumor , Cell Movement/drug effects , Neoplasm Metastasis , Disease Progression
16.
J Coll Physicians Surg Pak ; 34(5): 539-544, 2024 May.
Article in English | MEDLINE | ID: mdl-38720213

ABSTRACT

OBJECTIVE: To determine the frequency of different types of acute leukaemia and their subtypes along with associated aberrant CD markers. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Immunology Armed Forces Institute of Pathology, National University of Medical Sciences, Rawalpindi, Pakistan, from November 2021 to October 2023. METHODOLOGY: All samples received for flow cytometric immunophenotyping with suspicion of acute leukaemia were included in the study. Cells were stained with fluorochrome labelled monoclonal antibodies against lineage-specific cluster of differentiation (CD) markers through a lyse-wash procedure. Acquisition and analysis were done using multi-parameter BD FACS Canto II Flow cytometer and BD FACS Diva software, respectively. Data were entered and analysed using SPSS v 23.0. RESULTS: Over a period of 2 years, a total of 1,115 suspected patients were tested for acute leukaemia. Among them, 728 (65.3%) were males and 387 (34.7%) were females, with mean age 28 ± 21 years, ranging from 1 week to 87 years. Among a total of 875/1115 (78.5%) diagnosed cases of acute leukaemia, AML was the most common leukaemia present in 408/875 (46.6%) patients followed by B-ALL and T-ALL in 384/875 (43.8%) and 70/87 (8%) patients, respectively (p = 0.5712). Aberrant CD markers were detected in 109/875 (12.5%) leukaemias (p = 0.0628). The most common aberrant CD markers in B-ALL were CD13 and CD33 present in 30/384 (7.8%) cases separately. Among AML and T-ALL most common aberrant CD markers were CD7 and CD33 present in 25/408 (6.13%) and 7/70 (10%) cases, respectively. CONCLUSION: Special consideration should be given to the presence of aberrant CD markers when assigning lineages to acute leukaemias. They may be important diagnostic, prognostic, and management tools for institution of immunotherapy. KEY WORDS: Aberrant CD markers, Acute leukaemia, CD Markers, Flow cytometry, Immunophenotyping.


Subject(s)
Flow Cytometry , Immunophenotyping , Humans , Female , Male , Adult , Middle Aged , Child , Adolescent , Aged , Child, Preschool , Young Adult , Antigens, CD , Infant , Aged, 80 and over , Pakistan , Leukemia/diagnosis , Infant, Newborn , Leukemia, Myeloid, Acute/diagnosis , Biomarkers, Tumor , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
17.
BMC Plant Biol ; 24(1): 423, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38760709

ABSTRACT

BACKGROUND: Soil salinity is one of the major menaces to food security, particularly in dealing with the food demand of the ever-increasing global population. Production of cereal crops such as wheat is severely affected by soil salinity and improper fertilization. The present study aimed to examine the effect of selected microbes and poultry manure (PM) on seedling emergence, physiology, nutrient uptake, and growth of wheat in saline soil. A pot experiment was carried out in research area of Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan. Saline soil (12 dS m- 1 w/w) was developed by spiking using sodium chloride, and used in experiment along with two microbial strains (i.e., Alcaligenes faecalis MH-2 and Achromobacter denitrificans MH-6) and PM. Finally, wheat seeds (variety Akbar-2019) were sown in amended and unamended soil, and pots were placed following a completely randomized design. The wheat crop was harvested after 140 days of sowing. RESULTS: The results showed a 10-39% increase (compared to non-saline control) in agronomic, physiological, and nutritive attributes of wheat plants when augmented with PM and microbes. Microbes together with PM significantly enhanced seedling emergence (up to 38%), agronomic (up to 36%), and physiological (up to 33%) in saline soil as compared to their respective unamended control. Moreover, the co-use of microbes and PM also improved soil's physicochemical attributes and enhanced N (i.e., 21.7%-17.1%), P (i.e., 24.1-29.3%), and K (i.e., 28.7%-25.3%) availability to the plant (roots and shoots, respectively). Similarly, the co-use of amendments also lowered the Na+ contents in soil (i.e., up to 62%) as compared to unamended saline control. This is the first study reporting the effects of the co-addition of newly identified salt-tolerant bacterial strains and PM on seedling emergence, physiology, nutrient uptake, and growth of wheat in highly saline soil. CONCLUSION: Our findings suggest that co-using a multi-trait bacterial culture and PM could be an appropriate option for sustainable crop production in salt-affected soil.


Subject(s)
Manure , Poultry , Salinity , Soil , Triticum , Triticum/growth & development , Soil/chemistry , Animals , Soil Microbiology , Seedlings/growth & development , Fertilizers/analysis , Alcaligenes faecalis/growth & development
19.
Cureus ; 16(4): e59066, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38800192

ABSTRACT

BACKGROUND: Apnea-hypopnea index (AHI) and nadir oxygen saturation (SpO2) are the indexes used to measure the severity of obstructive sleep apnea (OSA). Obesity, measured by body mass index (BMI), is one of the main contributing factors to the onset and severity of OSA in patients. This study was conducted to find the association between BMI and OSA severity indexes, mainly AHI and nadir SpO2 levels. METHODS: Polysomnography reports of patients with diagnosed OSA in a teaching hospital were retrospectively reviewed. BMI, AHI, and nadir SpO2 levels were recorded from the sleep study reports of the patients. Spearman's Rho test was applied to find the correlation between BMI and AHI/nadir Spo2 levels. RESULTS: A total of 167 patients were included in the study, comprising 83 males and 84 females. The Mann-Whitney U test was utilized to investigate the association between BMI and gender and age groups. The analysis revealed a significant difference in BMI between males and females, with females having a higher BMI. However, there was no significant difference in BMI among individuals in the early middle and late middle age groups. Spearman's Rho test was employed to explore the correlation between BMI and AHI/nadir SpO2 levels. The results indicated no significant correlation between BMI and AHI (p = .122) or nadir SpO2 levels (p = .239). CONCLUSION: Contrary to common belief, BMI was not linked to the severity of OSA. It implies that several other factors, independent of BMI, play a role in the disease progression and severity.

20.
PLoS One ; 19(5): e0303426, 2024.
Article in English | MEDLINE | ID: mdl-38805437

ABSTRACT

This paper aims to extend the applications of the projected fractional improved Adomian Decomposition method (fIADM) to the fractional order new coupled Korteweg-de Vries (cKdV) system. This technique is significantly recognized for its effectiveness in addressing nonlinearities and iteratively handling fractional derivatives. The approximate solutions of the fractional-order new cKdV system are obtained by employing the improved ADM in fractional form. These solutions play a crucial role in designing and optimizing systems in engineering applications where accurate modeling of wave phenomena is essential, including fluid dynamics, plasma physics, nonlinear optics, and other mathematical physics domains. The fractional order new cKdV system, integrating fractional calculus, enhances accuracy in modeling wave interactions compared to the classical cKdV system. Comparison with exact solutions demonstrates the high accuracy and ease of application of the projected method. This proposed technique proves influential in resolving fractional coupled systems encountered in various fields, including engineering and physics. Numerical results obtained using Mathematica software further verify and demonstrate its efficacy.


Subject(s)
Algorithms , Models, Theoretical , Nonlinear Dynamics , Software , Computer Simulation
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