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1.
Drug Res (Stuttg) ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38991530

ABSTRACT

BACKGROUND AND PURPOSE: SGLT2 inhibitors are class of drugs that are used in adults with type 2 diabetes through a novel mechanism of action by reducing renal tubular glucose reabsorption, leading to a reduction in blood glucose without stimulating insulin release. In this systematic review, we report the effects of treatment with SGLT2 inhibitors on urinary tract infection (UTI) and genitourinary infection (GUI). METHOD: The study integrated data from landmark trials of SGLT2 inhibitors (CANVAS, CREDENCE, DECLARE-TIMI 58, and EMPA-REG) to interpret the association of SGLT2 inhibitors with genital infection (GI) and UTI. We reported the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was a composite of participants reporting UTI and GUI prescribed on SGLT2 inhibitors. RESULTS: The analysis of four studies involving 38,723 participants revealed incidences of both UTIs and GUI. In the SGLT2 inhibitor group, comprising 21,266 participants, 222 (1.04%) experienced UTIs, and 477 (2.24%) reported GUI. In contrast, among the placebo group consisting of 17,457 participants, 201 (1.15%) reported UTIs, and 70 (0.40%) reported genital infections. These findings underscore the elevated risk associated with SGLT2 inhibitor use, particularly regarding GUI, necessitating careful consideration in clinical practice and patient management strategies. CONCLUSION: The incidence of UTIs and particularly more pronounced GUI associated with SGLT2 inhibitors highlights the importance of careful risk assessment and monitoring in clinical decision-making, underscoring the need for patient management strategies.

3.
BMJ Case Rep ; 17(5)2024 May 28.
Article in English | MEDLINE | ID: mdl-38806401

ABSTRACT

Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder caused by uncontrolled activation of the immune system, leading to phagocytosis of blood cells and cytokine storm. HLH can manifest in childhood due to a genetic mutation, but in adults HLH arises secondary to viral infections, autoimmune diseases or neoplastic processes. The most common viral infections associated with HLH are Epstein-Barr virus (EBV) and cytomegalovirus (CMV). EBV and CMV coinfection associated with HLH, however, is exceedingly rare. We present a case of HLH secondary to EBV and CMV coinfection in a young adult who presented with recurrent intermittent high-grade fevers and epistaxis. This case illustrates the importance of considering HLH in patients with idiopathic fevers and to consider all the potential aetiologies for HLH to ensure proper treatment.


Subject(s)
Coinfection , Cytomegalovirus Infections , Epstein-Barr Virus Infections , Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/virology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Male , Herpesvirus 4, Human , Antiviral Agents/therapeutic use , Cytomegalovirus , Adult
4.
BMJ Case Rep ; 17(3)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38471704

ABSTRACT

HIV-associated myopathies include HIV-associated polymyositis, inclusion body myositis, diffuse infiltrative lymphocytosis syndrome and sporadic late-onset nemaline myopathy (HIV-NM). HIV-NM typically manifests as a painless, progressive proximal and axial muscle weakness with characteristic histological findings of intracytoplasmic rods, or nemaline bodies, seen in atrophic muscle fibres. HIV-NM presents prior to or shortly after initiation of antiretroviral therapy (ART) and is treated with intravenous immunoglobulin, glucocorticoids or immunosuppression. We present a case of HIV-NM in a patient with well-controlled HIV on decades-long ART with progressive bent spine syndrome, or camptocormia. This case highlights the importance of considering HIV-associated myopathies such as HIV-NM in patients with HIV who present with musculoskeletal complaints.


Subject(s)
HIV Infections , Muscular Atrophy, Spinal , Myopathies, Nemaline , Myositis, Inclusion Body , Spinal Curvatures , Humans , HIV Infections/complications , Muscle Fibers, Skeletal , Muscle, Skeletal/pathology , Myopathies, Nemaline/complications , Myopathies, Nemaline/pathology , Myopathies, Nemaline/therapy
5.
BMC Res Notes ; 17(1): 16, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38178164

ABSTRACT

OBJECTIVE: The quality of dried blood spot (DBS) specimens impacts newborn screening (NBS) results, hence proper training is crucial for DBS specimen collection. To address this, a training module for Allied Health Professionals (AHPs) and nurses was created on Moodle, a virtual learning environment (VLE). The purpose of this research was to determine the feasibility and effectiveness of this module. METHODOLOGY: Participants were trained on-site (March to December 2019), through online training sessions (January to June 2020), and the two training strategies were compared. Data analysis included the total number of participants, cost-effectiveness, trainer engagement, and the number of unacceptable samples collected by nurses/AHPs trained by the two strategies. RESULTS: A total of 55 nurses/AHPs were trained on-site, while 79 nurses/AHPs completed the online module and received certificates through online VLE-based training. The trainer engagement and cost were more for onsite training. After online training, the specimen rejection rate was reduced from 0.84% (44 rejected out of 5220 total specimens collected) to 0.38% (15/3920). CONCLUSIONS: This study shows that using VLE-based DBS specimen collection training is feasible and effective for training nurses and AHPs.


Subject(s)
Education, Distance , Infant, Newborn , Humans , Cross-Sectional Studies , Specimen Handling , Blood Specimen Collection
6.
Eur Spine J ; 33(2): 563-570, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37768339

ABSTRACT

PURPOSE: The mechanical complications related to ASD remain a concern due to their morbidity and associated revision surgery. Restoration of each patient's Roussouly profile may reduce these. Our aim was to examine if the restoration of the Roussouly profile reduced these complications and revision rates in older patients operated for degenerative ASD. METHODS: Retrospective analysis of a single-centre, 2-year minimum follow-up patient database. All patients undergoing corrective surgery (≥ 4 levels) for ASD were included with analysis of demographic data, operative records, restoration of Roussouly sagittal profile, mechanical complications and revision rates. Univariate and multivariate analysis was conducted. RESULTS: Fifty-two patients were included (mean age was 72.3 years, average follow-up 56.3 months). Twenty-six patients had a "restored" profile (50%) and 26 an "unrestored" profile (50%). The incidence of mechanical complications was 7 (27%) and 23 (88%) for the restored and unrestored groups, respectively (p < 0.001). Revision rates were 4 (15.4%) and 18 (69.2%), respectively (p < 0.000), in the restored and unrestored profiles. Univariate analysis determined that profile restoration and BMI were associated with mechanical complications and revision surgery, whilst only the profile restoration status maintained its statistical power in multivariate analysis (p = 0.002 and p = 0.002, respectively). Age was not a significant factor in univariate analysis. The relative risk for mechanical failure and revision surgery was 5.6 times (CI 1.929-16.39) and 3.08 times (CI 1.642-5.734) greater if the profile was not restored. CONCLUSIONS: Achieving each patient's ideal Roussouly profile is associated with a reduced incidence of mechanical complications and revision rates in the older population after surgery for degenerative ASD.


Subject(s)
Dioctyl Sulfosuccinic Acid , Adult , Humans , Aged , Reoperation , Retrospective Studies , Databases, Factual , Multivariate Analysis
7.
BMJ Case Rep ; 16(11)2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37945272

ABSTRACT

Mycobacterium xenopi is a non-tuberculous mycobacterium (NTM) that sporadically causes infections in humans and can cause rare bone and joint infections in immunocompromised hosts with history of spinal surgery. This slow-growing mycobacterium takes 8-12 weeks to grow on culture. Metagenomic next-generation sequencing (MNGS) is a highly sensitive and specific plasma-based microbial cell-free DNA test that can detect M. xenopi weeks prior to culture growth. We present a case of M. xenopi lumbosacral discitis with presacral abscess in an immunocompromised woman without history of spinal surgery which was detected by MNGS 8 weeks prior to culture growth. The patient's discitis resolved with an M. xenopi-directed regimen of ethambutol, rifampin and azithromycin. This case illustrates the utility of next-generation sequencing tests in rapid diagnosis of rare and opportunistic infections, as compared with traditional diagnostic tests, with supporting contextual clinical and diagnostic findings.


Subject(s)
Discitis , Mycobacterium Infections, Nontuberculous , Mycobacterium xenopi , Mycobacterium , Female , Humans , Discitis/diagnosis , Discitis/drug therapy , Discitis/microbiology , Ethambutol , High-Throughput Nucleotide Sequencing , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium xenopi/genetics , Middle Aged
8.
BMJ Case Rep ; 16(8)2023 Aug 27.
Article in English | MEDLINE | ID: mdl-37640411

ABSTRACT

Cutaneous lymphoproliferative disorders include cutaneous manifestations of systemic B-cell or T-cell lymphoma and primary cutaneous lymphomas. Primary cutaneous B-cell lymphomas are subcategorised into four groups: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg-type and EBV-positive mucocutaneous tumour. Each of these cutaneous lymphoproliferative disorders has unique clinical and pathological features necessitating biopsy and staging to establish proper treatment. We present a case of PCMZL manifesting as secondary chilblains of the toes that was diagnosed with punch skin biopsy. The patient's chilblains resolved with rituximab. This case underscores the importance of considering PCMZL and other cutaneous lymphoproliferative disorders in patients with dermatological manifestations and wounds refractory to first-line treatment.


Subject(s)
Chilblains , Lymphoma, T-Cell , Humans , Lower Extremity , Toes , B-Lymphocytes
9.
BMJ Case Rep ; 16(8)2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37580096

ABSTRACT

The anterior cruciate ligament (ACL) is the most frequently injured knee ligament, typically in non-contact athletic injuries in young adults. Mucoid degeneration of the ACL (ACL-MD) is an uncommon ACL pathology in which glycosaminoglycans deposition within the collagenous bundles leads to hypertrophy, loss of full knee flexion and knee pain without instability. ACL-MD usually presents in individuals over 40 years with sudden-onset knee pain after minimal trauma or as an incidental MRI finding. ACL-MD is rarely described in young adults. We present a case of ACL-MD in a previously healthy adult in his early 20s who presented with 3-month recalcitrant dull left knee pain and limited range of motion after 'stepping funny' with slight twisting. This case highlights the need to critically reflect on the anatomical structures when presented with musculoskeletal pathologies and to consider the unique presentation of musculoskeletal disease in atypical age groups.


Subject(s)
Anterior Cruciate Ligament Injuries , Joint Instability , Young Adult , Humans , Anterior Cruciate Ligament/diagnostic imaging , Anterior Cruciate Ligament/surgery , Autografts , Knee Joint/diagnostic imaging , Knee Joint/surgery , Anterior Cruciate Ligament Injuries/diagnostic imaging , Anterior Cruciate Ligament Injuries/surgery , Pain , Range of Motion, Articular
10.
Trop Anim Health Prod ; 55(4): 276, 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37500805

ABSTRACT

This study aimed to utilize the XGBoost and MARS algorithms to predict present weight from body measurements. The algorithms have the potential to model nonlinear relationships between body measurements and weight, and this study attempted to find a model that provided the most accurate predictions of present weight. The current study was conducted with 152 animals in order to achieve a certain goal. To compare the model performances, goodness-of-fit criteria such as R2, r, RMSE, CV, SDratio, PI, MAPE, AIC were used. According to the results of this study, the XGBoost algorithm was the most reliable model for predicting present weight from body measurement. Even if the XGBoost algorithm was the most accurate model, the MARS algorithm was the reliable model for the same aim. In addition, it is hoped that the results of this study will help researchers and breeders better understand the relationship between body measurements and weight and ultimately be able to help individuals better manage their weight. As a conclusion, in the current study, the XGBoost algorithm is an effective, efficient, and reliable tool for accurately estimating present weight from body measurements. This makes it an invaluable tool in rural areas, where traditional weighing scales may not be available or reliable.


Subject(s)
Algorithms , Animals , Sheep , Body Weight
11.
SN Appl Sci ; 5(5): 152, 2023.
Article in English | MEDLINE | ID: mdl-37153442

ABSTRACT

Abstract: This paper presents a hierarchical approach for controlling the spread of an epidemic disease. The approach consists of a three-layer architecture where a set of two-layer multiple social networks is governed by a (third) top-layer consisting of an optimal control policy. Each of the two-layer social networks is modeled by a microscopic Markov chain. On top of all the two-layer networks is an optimal control policy that has been developed by using an underlying Markov Decision Process (MDP) model. Mathematical models pertaining to the top-level MDP as well as two-layer microscopic Markov chains have been presented. Practical implementation methodology using the proposed models has also been discussed along with a numerical example. The results in the numerical example illustrate the control of an epidemic using the optimal policy. Directions for further research and characterization of the optimal policy have also been discussed with the help of the same numerical example. Article Highlights: An optimal approach for controlling the spread of an epidemic infection.The approach is able to model the uncertainties involved in the problem.The approach is able to cater for the underlying social network.

12.
Plants (Basel) ; 12(8)2023 Apr 15.
Article in English | MEDLINE | ID: mdl-37111885

ABSTRACT

Sorghum (Sorghum bicolor) is the fifth most important cereal crop worldwide; however, its utilization in food products can be limited due to reduced nutritional quality related to amino acid composition and protein digestibility in cooked products. Low essential amino acid levels and digestibility are influenced by the composition of the sorghum seed storage proteins, kafirins. In this study, we report a core collection of 206 sorghum mutant lines with altered seed storage proteins. Wet lab chemistry analysis was conducted to evaluate the total protein content and 23 amino acids, including 19 protein-bound and 4 non-protein amino acids. We identified mutant lines with diverse compositions of essential and non-essential amino acids. The highest total protein content in these lines was almost double that of the wild-type (BTx623). The mutants identified in this study can be used as a genetic resource to improve the sorghum grain quality and determine the molecular mechanisms underlying the biosynthesis of storage protein and starch in sorghum seeds.

13.
Int J Mol Sci ; 24(7)2023 Mar 23.
Article in English | MEDLINE | ID: mdl-37047009

ABSTRACT

Climate changes abruptly affect optimum growth temperatures, leading to a negative influence on plant physiology and productivity. The present study aimed to investigate the extent of low-temperature stress effects on date palm growth and physiological indicators under the exogenous application of silicon (Si). Date palm seedlings were treated with Si (1.0 mM) and exposed to different temperature regimes (5, 15, and 30 °C). It was observed that the application of Si markedly improved fresh and dry biomass, photosynthetic pigments (chlorophyll and carotenoids), plant morphology, and relative water content by ameliorating low-temperature-induced oxidative stress. Low-temperature stress (5 and 15 °C), led to a substantial upregulation of ABA-signaling-related genes (NCED-1 and PyL-4) in non Si treated plants, while Si treated plants revealed an antagonistic trend. However, jasmonic acid and salicylic acid accumulation were markedly elevated in Si treated plants under stress conditions (5 and 15 °C) in comparison with non Si treated plants. Interestingly, the upregulation of low temperature stress related plant plasma membrane ATPase (PPMA3 and PPMA4) and short-chain dehydrogenases/reductases (SDR), responsible for cellular physiology, stomatal conductance and nutrient translocation under silicon applications, was observed in Si plants under stress conditions in comparison with non Si treated plants. Furthermore, a significant expression of LSi-2 was detected in Si plants under stress, leading to the significant accumulation of Si in roots and shoots. In contrast, non Si plants demonstrated a low expression of LSi-2 under stress conditions, and thereby, reduced level of Si accumulation were observed. Less accumulation of oxidative stress was evident from the expression of superoxide dismutase (SOD) and catalase (CAT). Additionally, Si plants revealed a significant exudation of organic acids (succinic acid and citric acid) and nutrient accumulation (K and Mg) in roots and shoots. Furthermore, the application of Si led to substantial upregulation of the low temperature stress related soybean cold regulated gene (SRC-2) and ICE-1 (inducer of CBF expression 1), involved in the expression of CBF/DREB (C-repeat binding factor/dehydration responsive element binding factor) gene family under stress conditions in comparison with non Si plants. The current research findings are crucial for exploring the impact on morpho-physio-biochemical attributes of date palms under low temperature and Si supplementation, which may provide an efficient strategy for growing plants in low-temperature fields.


Subject(s)
Phoeniceae , Silicon , Silicon/pharmacology , Silicon/metabolism , Phoeniceae/genetics , Phoeniceae/metabolism , Antioxidants/pharmacology , Temperature , Oxidative Stress
14.
BMJ Case Rep ; 16(3)2023 Mar 24.
Article in English | MEDLINE | ID: mdl-36963765

ABSTRACT

Severe acute hyponatraemia, defined as a sodium concentration of less than 120 mEq/L, typically manifests with neurological manifestations, resulting in obtundation, coma, seizures, respiratory arrest and death. It very rarely is arrhythmogenic, with a literature review revealing seven cases of hyponatraemia-associated atrioventricular (AV) block of various degrees, of which only three were described as having third-degree AV block. The higher-degree AV blocks typically occurred at sodium levels closer to 115 mEq/L. We present a case of severe acute hypo-osmolar hyponatraemia-induced third-degree AV block in a patient without any other risk factors or aetiologies who initially presented with subdural haematoma and developed refractory bradycardia during his admission. The patient's third-degree AV block completely resolved after correction of his sodium. This case highlights the importance of working up the cause of new-onset third-degree AV block and the consideration of rarer electrolyte derangements such as hyponatraemia as a potential cause.


Subject(s)
Atrioventricular Block , Hyponatremia , Humans , Atrioventricular Block/complications , Atrioventricular Block/therapy , Hyponatremia/etiology , Arrhythmias, Cardiac/complications , Bradycardia , Sodium
15.
SAGE Open Med ; 11: 20503121221148613, 2023.
Article in English | MEDLINE | ID: mdl-36741931

ABSTRACT

Objective: Vitamin D deficiency in Chronic Kidney Disease is a known fact, but the data regarding the prevalence and extent of vitamin D deficiency in different stages of Chronic Kidney Disease is scarce. This leads to a delay in addressing this issue. We conducted this study to assess vitamin-D deficiency in different stages of Chronic Kidney Disease to improve the evidence available to Physicians and Nephrologists which can help them better address this common finding in Chronic Kidney Disease. Methods: This retrospective study from a tertiary care hospital in Karachi, Pakistan, included adult Chronic Kidney Disease patients who had their serum 25 Hydroxy vitamin D levels done. The patients were classified according to stages of Chronic Kidney Disease using Estimated Glomerular Filtration Rate values. Appropriate statistical tests were performed to find a correlation between the severity of vitamin D deficiency in different stages of Chronic Kidney Disease with a statistically significant p value of <0.05 and a 95% confidence interval. Results: In total, 148 patients were included in the study. All patients had serum 25 Hydroxy vitamin D levels less than 30 ng/ml. The severity of vitamin D deficiency was observed to increase progressively from stage 3A Chronic Kidney Disease through stage 5. Vitamin D levels in Chronic Kidney Disease stage 3 were significantly greater than in Chronic Kidney Disease stages 4 and 5 (p value < 0.001), and stage 5 patients had the lowest vitamin D levels in our study. Similar, statistically significant findings were observed for serum phosphate levels, too, with stage 5 Chronic Kidney Disease patients having a greater serum phosphate concentration than stages 3A and 3B (p value = 0.002, 0.006). Conclusion: All Chronic Kidney Disease patients in our study either had vitamin D insufficiency or deficiency. In addition, we observed a significant decrease in vitamin D levels from Chronic Kidney Disease stage 3 to stage 5. Greater serum phosphate levels were detected in stage 5 compared to stages 3A and 3B.

16.
J Fungi (Basel) ; 9(2)2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36836368

ABSTRACT

Cochliobolus, Bipolaris, and Curvularia genera contain various devastating plant pathogens that cause severe crop losses worldwide. The species belonging to these genera also perform a variety of diverse functions, including the remediation of environmental contaminations, beneficial phytohormone production, and maintaining their lifestyle as epiphytes, endophytes, and saprophytes. Recent research has revealed that despite their pathogenic nature, these fungi also play an intriguing role in agriculture. They act as phosphate solubilizers and produce phytohormones, such as indole acetic acid (IAA) and gibberellic acid (GAs), to accelerate the growth of various plants. Some species have also been reported to play a significant role in plant growth promotion during abiotic stresses, such as salinity stress, drought stress, heat stress, and heavy metal stress, as well as act as a biocontrol agent and a potential mycoherbicide. Similarly, these species have been reported in numerous industrial applications to produce different types of secondary metabolites and biotechnological products and possess a variety of biological properties, such as antibacterial, antileishmanial, cytotoxic, phytotoxic, and antioxidant activities. Additionally, some of the species have been utilized in the production of numerous valuable industrial enzymes and biotransformation, which has an impact on the growth of crops all over the world. However, the current literature is dispersed, and some of the key areas, such as taxonomy, phylogeny, genome sequencing, phytohormonal analysis, and diversity, are still being neglected in terms of the elucidation of its mechanisms, plant growth promotion, stress tolerance, and bioremediation. In this review, we highlighted the potential role, function, and diversity of Cochliobolus, Curvularia, and Bipolaris for improved utilization during environmental biotechnology.

17.
Front Immunol ; 13: 1004804, 2022.
Article in English | MEDLINE | ID: mdl-36311762

ABSTRACT

The current global outbreak of monkeypox (MPX) disease, caused by Monkeypox virus (MPXV), has resulted in 16 thousand infection cases, five deaths, and has been declared a global health emergency of international concern by the World Health Organization. Given current challenges in the safety of existing vaccines, a vaccine to prevent MPX infection and/or onset of symptoms would significantly advance disease management. In this context, a multi-epitope-based vaccine could be a well-suited approach. Herein, we searched a publicly accessible database (Virus Pathogen Database and Analysis Resource) for MPXV immune epitopes from various antigens. We prioritized a group of epitopes (10 CD8+ T cells and four B-cell epitopes) using a computer-aided technique based on desirable immunological and physicochemical properties, sequence conservation criteria, and non-human homology. Three multi-epitope vaccines were constructed (MPXV-1-3) by fusing finalized epitopes with the aid of appropriate linkers and adjuvant (beta-defensin 3, 50S ribosomal protein L7/L12, and Heparin-binding hemagglutinin). Codon optimization and in silico cloning in the pET28a (+) expression vector ensure the optimal expression of each construct in the Escherichia Coli system. Two and three-dimensional structures of the constructed vaccines were predicted and refined. The optimal binding mode of the construct with immune receptors [Toll-like receptors (TLR2, TLR3, and TLR4)] was explored by molecular docking, which revealed high docking energies of MPXV-1-TLR3 (-99.09 kcal/mol), MPXV-2-TLR3 (-98.68 kcal/mol), and MPXV-3-TLR2 (-85.22 kcal/mol). Conformational stability and energetically favourable binding of the vaccine-TLR2/3 complexes were assessed by performing molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). In silico immune simulation suggested that innate, adaptive, and humoral responses will be elicited upon administration of such potent multi-epitope vaccine constructs. The vaccine constructs are antigenic, non-allergen, non-toxic, soluble, topographically exposed, and possess favourable physicochemical characteristics. These results may help experimental vaccinologists design a potent MPX vaccine.


Subject(s)
Epitopes, T-Lymphocyte , Mpox (monkeypox) , Humans , Vaccines, Subunit , Molecular Docking Simulation , Toll-Like Receptor 2 , Toll-Like Receptor 3 , Amino Acid Sequence , Computational Biology/methods
18.
Molecules ; 27(16)2022 Aug 15.
Article in English | MEDLINE | ID: mdl-36014440

ABSTRACT

The present analysis explores the chemical constituents and determines the in vitro antimicrobial, antidiabetic, and antioxidant significance of the essential oils (EOs) of the stem, leaves, and flowers of Ochradenus arabicus for the first time. The EOs of the flowers presented seventy-four constituents contributing to 81.46% of the total EOs, with the major compounds being 24-norursa-3,12-diene (13.06%), 24-norursa-3,12-dien-11-one (6.61%), and 24-noroleana-3,12-diene (6.25%). The stem EOs with sixty-one compounds contributed 95.95% of the total oil, whose main bioactive compounds were (+)-camphene (21.50%), eremophilene (5.87%), and δ-selinene (5.03%), while a minimum of fifty-one compounds in the leaves' EOs (98.75%) were found, with the main constituents being n-hexadecanoic acid (12.32%), octacosane (8.62%), tetradecanoic acid (8.54%), and prehydro fersenyl acetone (7.27%). The antimicrobial activity of the EOs of O. arabicus stem, leaves, and flowers was assessed against two bacterial strains (Escherichia coli and Streptococcus aureus) and two fungal strains (Penicillium simplicissimum and Rhizoctonia solani) via the disc diffusion assay. However, the EOs extracted from the stem were found effective against one bacterial strain, E. coli, and one fungal strain, R. Solani, among the examined microbes in comparison to the standard and negative control. The tested EOs samples of the O. arabicus stem displayed a maximum potential to cure diabetes with an IC50 = 0.40 ± 0.10 µg/mL, followed by leaves and flowers with an IC50 = 0.71 ± 0.11 µg/mL and IC50 = 10.57 ± 0.18 µg/mL, respectively, as compared to the standard acarbose (IC50 = 377.26 ± 1.20 µg/mL). In addition, the EOs of O. arabicus flowers had the highest antioxidant activity (IC50 = 106.40 ± 0.19 µg/mL) as compared to the standard ascorbic acid (IC50 = 73.20 ± 0.17 µg/mL) using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In the ABTS assay, the EOs of the same sample (flower) depicted the utmost potential to scavenge the free radicals with an IC50 = 178.0 ± 0.14 µg/mL as compared with the ascorbic acid, having an IC50 of 87.34 ± 0.10 µg/mL the using 2,2-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic acid (ABTS) assay. The EOs of all parts of O. arabicus have useful bioactive components due to which they present antidiabetic and antioxidant significance. Furthermore, additional investigations are considered necessary to expose the responsible components of the examined biological capabilities, which would be effective in the production of innovative drugs.


Subject(s)
Oils, Volatile , Resedaceae , Anti-Bacterial Agents/chemistry , Antioxidants/chemistry , Ascorbic Acid/analysis , Bacteria , Escherichia coli , Flowers/chemistry , Hypoglycemic Agents/pharmacology , Odorants , Oils, Volatile/chemistry
19.
Int J Mol Sci ; 23(4)2022 Feb 19.
Article in English | MEDLINE | ID: mdl-35216429

ABSTRACT

Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models.


Subject(s)
Benzoquinones/pharmacology , Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Glycolysis/drug effects , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Colorectal Neoplasms/metabolism , HCT116 Cells , Hexokinase/metabolism , Humans , Nigella sativa/drug effects , Nigella sativa/metabolism , Signal Transduction/physiology
20.
Curr Diabetes Rev ; 18(3): e120721194712, 2022.
Article in English | MEDLINE | ID: mdl-34931983

ABSTRACT

BACKGROUND: Diabetes mellitus (DM) is among the most frequently reported comorbidities in patients tainted with the pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a high pervasiveness of diabetes mellitus, there is an urgency to understand the special aspects of COVID-19 in hyperglycemic patients. Diabetic patients are at higher risk than the general population of viral or bacterial infections, thus require special attention since diabetes is linked with severe, critical, and lethal modes of COVID-19. OBJECTIVE: The objective of this study was to focus on epidemiology, pathophysiology, mechanism, and management of DM with COVID-19. METHODS: The search was carried out on databases portals such as Pubmed, EMBASE, Google Scholar, and CINAHL with the keywords, i.e., COVID-19, coronavirus, SARS-CoV-2, diabetes, covid-19, etc. Result: DM and COVID-19 disease conditions can impact each other in terms of clinical progression and outcome. Available laboratory/clinical observations suggest that hyperglycemia-induced immune dysfunction, inflated lactate grades, and cytokines storm may play critical roles in the seriousness of COVID-19 in patients with diabetes; however, the exact mechanisms linking diabetes and COVID-19 remain to be further clarified. CONCLUSION: Standards to constrain the disease spread at the individual and community level are the key to extenuate the speedily rising pandemic, while definitive treatment, like plasma therapy, chemoprophylaxis, or vaccine for COVID-19, has yet to be discovered.


Subject(s)
COVID-19 , Diabetes Mellitus , COVID-19/epidemiology , COVID-19/therapy , COVID-19 Vaccines , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Humans , Pandemics , Prevalence , SARS-CoV-2
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