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2.
Int J Mol Sci ; 25(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38928168

ABSTRACT

Drought stress is one of the most severe natural disasters in terms of its frequency, length, impact intensity, and associated losses, making it a significant threat to agricultural productivity. Sorghum (Sorghum bicolor), a C4 plant, shows a wide range of morphological, physiological, and biochemical adaptations in response to drought stress, paving the way for it to endure harsh environments. In arid environments, sorghum exhibits enhanced water uptake and reduced dissipation through its morphological activity, allowing it to withstand drought stress. Sorghum exhibits physiological and biochemical resistance to drought, primarily by adjusting its osmotic potential, scavenging reactive oxygen species, and changing the activities of its antioxidant enzymes. In addition, certain sorghum genes exhibit downregulation capabilities in response to drought stress. Therefore, in the current review, we explore drought tolerance in sorghum, encompassing its morphological characteristics and physiological mechanisms and the identification and selection of its functional genes. The use of modern biotechnological and molecular biological approaches to improving sorghum resistance is critical for selecting and breeding drought-tolerant sorghum varieties.


Subject(s)
Droughts , Gene Expression Regulation, Plant , Reactive Oxygen Species , Sorghum , Transcription Factors , Sorghum/genetics , Sorghum/metabolism , Reactive Oxygen Species/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Adaptation, Physiological/genetics
3.
Front Pharmacol ; 15: 1361679, 2024.
Article in English | MEDLINE | ID: mdl-38910889

ABSTRACT

Introduction: The members retinoic acid receptors (RARs) (α, ß, and γ) and retinoid X receptors (RXRs) (α, ß, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates. Objective: This study's main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients. Methodology: In-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells. Results: Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study. Discussion: Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.

4.
RSC Med Chem ; 15(6): 1877-1898, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38911170

ABSTRACT

Cancer is a complex disease and the second leading cause of death globally, and breast cancer is still a leading cause of cancer death in women. Tamoxifen is the most commonly used drug for breast cancer (ER-positive) treatment and chemoprevention, saving the lives of millions of patients every year. In addition, the tamoxifen template has been explored extensively for the development of selective estrogen receptor modulators (SERMs) applicable in breast cancer, osteoporosis, and postmenopausal symptom treatment. Numerous anticancer drugs, including tamoxifen, are in use, but the complexity and heterogeneous nature of cancer complicate the effect of conventional targeted drugs, leading to adverse reactions and resistance. One of the significant approaches to overcome these shortcomings is drug hybrids, generated by covalently linking two or more active pharmacophores. These drug hybrids are remarkably effective in acting on multiple drug targets with higher selectivity and specificity. In recent years, several tamoxifen hybrids have been discovered as potential candidates for cancer treatment. The review highlights the recent progress in developing anticancer hybrids, including organometallic, fluorescent, photocaged, and novel ligand-based tamoxifen hybrids. It also demonstrates the significance of merging various pharmacophores with tamoxifen to produce more potent, precise, and effective anticancer agents. The study offers valuable knowledge to researchers working on cancer research with the hope of enhancing drug potency and reducing drug toxicity to improve cancer patients' lives.

5.
Bioresour Bioprocess ; 11(1): 56, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825667

ABSTRACT

Produced water (PW) from oil and gas exploration adversely affects aquatic life and living organisms, necessitating treatment before discharge to meet effluent permissible limits. This study first used activated sludge to pretreat PW in a sequential batch reactor (SBR). The pretreated PW then entered a 13 L photobioreactor (PBR) containing Scenedesmus obliquus microalgae culture. Initially, 10% of the PW mixed with 90% microalgae culture in the PBR. After the exponential growth of the microalgae, an additional 25% of PW was added to the PBR without extra nutrients. This study reported the growth performance of microalgae in the PBR as well as the reduction in effluent's total organic carbon (TOC), total dissolved solids (TDS), electrical conductivity (EC), and heavy metals content. The results demonstrated removal efficiencies of 64% for TOC, 49.8% for TDS, and 49.1% for EC. The results also showed reductions in barium, iron, and manganese in the effluent by 95, 76, and 52%, respectively.

6.
Nutrients ; 16(10)2024 May 20.
Article in English | MEDLINE | ID: mdl-38794775

ABSTRACT

BACKGROUND: This study aims to identify unique metabolomics biomarkers associated with Type 2 Diabetes (T2D) and develop an accurate diagnostics model using tree-based machine learning (ML) algorithms integrated with bioinformatics techniques. METHODS: Univariate and multivariate analyses such as fold change, a receiver operating characteristic curve (ROC), and Partial Least-Squares Discriminant Analysis (PLS-DA) were used to identify biomarker metabolites that showed significant concentration in T2D patients. Three tree-based algorithms [eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Adaptive Boosting (AdaBoost)] that demonstrated robustness in high-dimensional data analysis were used to create a diagnostic model for T2D. RESULTS: As a result of the biomarker discovery process validated with three different approaches, Pyruvate, D-Rhamnose, AMP, pipecolate, Tetradecenoic acid, Tetradecanoic acid, Dodecanediothioic acid, Prostaglandin E3/D3 (isobars), ADP and Hexadecenoic acid were determined as potential biomarkers for T2D. Our results showed that the XGBoost model [accuracy = 0.831, F1-score = 0.845, sensitivity = 0.882, specificity = 0.774, positive predictive value (PPV) = 0.811, negative-PV (NPV) = 0.857 and Area under the ROC curve (AUC) = 0.887] had the slight highest performance measures. CONCLUSIONS: ML integrated with bioinformatics techniques offers accurate and positive T2D candidate biomarker discovery. The XGBoost model can successfully distinguish T2D based on metabolites.


Subject(s)
Biomarkers , Computational Biology , Diabetes Mellitus, Type 2 , Machine Learning , Metabolomics , Diabetes Mellitus, Type 2/metabolism , Humans , Biomarkers/blood , Computational Biology/methods , Pilot Projects , Male , Middle Aged , Female , Metabolomics/methods , ROC Curve , Algorithms , Aged , Adult
7.
PLoS One ; 19(4): e0287864, 2024.
Article in English | MEDLINE | ID: mdl-38626166

ABSTRACT

The fourth most frequent type of cancer in women and the leading cause of mortality for females worldwide is cervical cancer. Traditionally, medicinal plants have been utilized to treat various illnesses and ailments. The molecular docking method is used in the current study to look into the phytoconstituents of Juglans regia's possible anticancer effects on cervical cancer target proteins. This work uses the microarray dataset analysis of GSE63678 from the NCBI Gene Expression Omnibus database to find differentially expressed genes. Furthermore, protein-protein interactions of differentially expressed genes were constructed using network biology techniques. The top five hub genes (IGF1, FGF2, ESR1, MYL9, and MYH11) are then determined by computing topological parameters with Cytohubba. In addition, molecular docking research was performed on Juglans regia phytocompounds that were extracted from the IMPPAT database versus hub genes that had been identified. Utilizing molecular dynamics, simulation confirmed that prioritized docked complexes with low binding energies were stable.


Subject(s)
Juglans , Uterine Cervical Neoplasms , Humans , Female , Molecular Docking Simulation , Juglans/genetics , Juglans/chemistry , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/genetics , Microarray Analysis , Computational Biology/methods
8.
Plants (Basel) ; 13(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674566

ABSTRACT

Salinity is one of the major constraints to crop production. Rice is a main staple food and is highly sensitive to salinity. This study aimed to elucidate the effects of salt stress on physiological and agronomic traits of rice genotypes with contrasting salt tolerance. Six contrasting rice genotypes (DJWJ, JFX, NSIC, HKN, XD2H and HHZ), including three salt-tolerant and three salt-sensitive rice genotypes, were grown under two different salt concentrations (0 and 100 mmol L-1 NaCl solution). The results showed that growth, physiological and yield-related traits of both salt-sensitive and salt-tolerant rice were significantly affected by salt stress. In general, plant height, tiller number, dry weight and relative growth rate showed 15.7%, 11.2%, 25.2% and 24.6% more reduction in salt-sensitive rice than in salt-tolerant rice, respectively. On the contrary, antioxidant enzyme activity (superoxide dismutase, peroxidase, catalase), osmotic adjustment substances (proline, soluble protein, malondialdehyde (MDA)) and Na+ content were significantly increased under salt stress, and the increase was far higher in salt-tolerant rice except for MDA. Furthermore, grain yield and yield components significantly decreased under salt stress. Overall, the salt-sensitive rice genotypes showed a 15.3% greater reduction in grain yield, 5.1% reduction in spikelets per panicle, 7.4% reduction in grain-filling percentage and 6.1% reduction in grain weight compared to salt-tolerant genotypes under salt stress. However, a modest gap showed a decline in panicles (22.2% vs. 22.8%) and total spikelets (45.4% vs. 42.1%) between salt-sensitive and salt-tolerant rice under salinity conditions. This study revealed that the yield advantage of salt-tolerant rice was partially caused by more biomass accumulation, growth rate, strong antioxidant capacity and osmotic adjustment ability under salt stress, which contributed to more spikelets per panicle, high grain-filling percentage and grain weight. The results of this study could be helpful in understanding the physiological mechanism of contrasting rice genotypes' responses to salt stress and to the breeding of salt-tolerant rice.

9.
Front Pharmacol ; 15: 1361424, 2024.
Article in English | MEDLINE | ID: mdl-38576486

ABSTRACT

Among women, breast carcinoma is one of the most complex cancers, with one of the highest death rates worldwide. There have been significant improvements in treatment methods, but its early detection still remains an issue to be resolved. This study explores the multifaceted function of hyaluronan-mediated motility receptor (HMMR) in breast cancer progression. HMMR's association with key cell cycle regulators (AURKA, TPX2, and CDK1) underscores its pivotal role in cancer initiation and advancement. HMMR's involvement in microtubule assembly and cellular interactions, both extracellularly and intracellularly, provides critical insights into its contribution to cancer cell processes. Elevated HMMR expression triggered by inflammatory signals correlates with unfavorable prognosis in breast cancer and various other malignancies. Therefore, recognizing HMMR as a promising therapeutic target, the study validates the overexpression of HMMR in breast cancer and various pan cancers and its correlation with certain proteins such as AURKA, TPX2, and CDK1 through online databases. Furthermore, the pathways associated with HMMR were explored using pathway enrichment analysis, such as Gene Ontology, offering a foundation for the development of effective strategies in breast cancer treatment. The study further highlights compounds capable of inhibiting certain pathways, which, in turn, would inhibit the upregulation of HMMR in breast cancer. The results were further validated via MD simulations in addition to molecular docking to explore protein-protein/ligand interaction. Consequently, these findings imply that HMMR could play a pivotal role as a crucial oncogenic regulator, highlighting its potential as a promising target for the therapeutic intervention of breast carcinoma.

10.
Cell Commun Signal ; 22(1): 243, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671495

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death in women. Epicardial adipose tissue (EAT) secretes cytokines to modulate coronary artery function, and the release of fatty acids from EAT serves as a readily available energy source for cardiomyocytes. However, despite having beneficial functions, excessive amounts of EAT can cause the secretion of proinflammatory molecules that increase the instability of atherosclerotic plaques and contribute to CAD progression. Although exercise mitigates CAD, the mechanisms by which exercise impacts EAT are unknown. The Yucatan pig is an excellent translational model for the effects of exercise on cardiac function. Therefore, we sought to determine if chronic aerobic exercise promotes an anti-inflammatory microenvironment in EAT from female Yucatan pigs. METHODS: Sexually mature, female Yucatan pigs (n = 7 total) were assigned to sedentary (Sed, n = 3) or exercise (Ex, n = 4) treatments, and coronary arteries were occluded (O) with an ameroid to mimic CAD or remained non-occluded (N). EAT was collected for bulk (n = 7 total) and single nucleus transcriptomic sequencing (n = 2 total, 1 per exercise treatment). RESULTS: Based on the bulk transcriptomic analysis, exercise upregulated S100 family, G-protein coupled receptor, and CREB signaling in neurons canonical pathways in EAT. The top networks in EAT affected by exercise as measured by bulk RNA sequencing were SRC kinase family, fibroblast growth factor receptor, Jak-Stat, and vascular endothelial growth factor. Single nucleus transcriptomic analysis revealed that exercise increased the interaction between immune, endothelial, and mesenchymal cells in the insulin-like growth factor pathway and between endothelial and other cell types in the platelet endothelial cell adhesion molecule 1 pathway. Sub-clustering revealed nine cell types in EAT, with fibroblast and macrophage populations predominant in O-Ex EAT and T cell populations predominant in N-Ex EAT. Unlike the findings for exercise alone as a treatment, there were not increased interactions between endothelial and mesenchymal cells in O-Ex EAT. Coronary artery occlusion impacted the most genes in T cells and endothelial cells. Genes related to fatty acid metabolism were the most highly upregulated in non-immune cells from O-Ex EAT. Sub-clustering of endothelial cells revealed that N-Ex EAT separated from other treatments. CONCLUSIONS: According to bulk transcriptomics, exercise upregulated pathways and networks related to growth factors and immune cell communication. Based on single nucleus transcriptomics, aerobic exercise increased cell-to-cell interaction amongst immune, mesenchymal, and endothelial cells in female EAT. Yet, exercise was minimally effective at reversing alterations in gene expression in endothelial and mesenchymal cells in EAT surrounding occluded arteries. These findings lay the foundation for future work focused on the impact of exercise on cell types in EAT.


Subject(s)
Adipose Tissue , Pericardium , Physical Conditioning, Animal , Transcriptome , Animals , Female , Swine , Pericardium/metabolism , Adipose Tissue/metabolism , Transcriptome/genetics , Adaptive Immunity/genetics , Immunity, Innate , Cell Nucleus/metabolism , Coronary Artery Disease/metabolism , Coronary Artery Disease/genetics , Epicardial Adipose Tissue
11.
Chem Asian J ; 19(9): e202400074, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38545693

ABSTRACT

This work demonstrates the use of jute stick extract as a reducing and stabilizing agent for the synthesis of spherical gold nanoparticles (AuNPs). In UV-Vis spectroscopy, peak at 550 nm was used to confirm the formation of AuNPs. The spherical surface morphology of AuNPs was determined through SEM and TEM analysis. While XRD investigation revealed the crystallinity of the prepared AuNPs. To ensure the biocompatibility of synthesized AuNPs, a bacterial investigation was conducted with negative results towards bacterial strain. The, modified FTO with AuNPs were able to detect glucose in CV analysis and the constructed sensor displayed a wide linear range of 50 µM to 40 mM with a detection limit of 20 µM. Scan rate analysis was performed to determine the charge transfer coefficient (0.42) and Tafel slope (102 mV/decade). Furthermore, the interfacial surface mechanism is illustrated to understand the interaction of glucose with the electrode surface in an alkaline medium and the product formation through the dehydrogenation and hydrolysis process. The prepared sensor also showed good stability, reproducibility, and anti-interference capabilities. In the case of real sample analysis, we used a blood serum sample. A low RSD value (<10 %) suggests the practical use of AuNPs/FTO in real-life applications.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Electrodes , Fluorine , Gold , Metal Nanoparticles , Tin Compounds , Gold/chemistry , Metal Nanoparticles/chemistry , Fluorine/chemistry , Tin Compounds/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Glucose/analysis , Surface Properties , Humans , Blood Glucose/analysis , Particle Size
12.
Work ; 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38427520

ABSTRACT

BACKGROUND: Accurate assessment tools for work rehabilitation are essential in healthcare settings. Adapting the Work Rehabilitation Questionnaire (WORQ) to Arabic-speaking populations ensures effective evaluation and intervention for individuals with work-related disabilities. OBJECTIVE: To execute a cross-cultural adaptation of interview-administered version Work Rehabilitation Questionnaire -Arabic (WORQ-A) and assess the psychometric properties of WORQ-A in patients with musculoskeletal problems. METHODS: WORQ is mainly intended to assess the work functioning of persons who are involved in vocational rehabilitation. Psychometric properties were scrutinized in the outpatient rehabilitation center. Test-retest reliability was examined with intraclass correlation coefficient (ICC), and internal consistency was evaluated with Cronbach's alpha. The usability of WORQ-A was established in 46 patients with musculoskeletal problems. RESULTS: WORQ-A exhibited exceptional internal consistency (0.93) and a great test-retest reliability (0.87). Regarding usability, the ability to understand the questions and answer choices was established as good. Five percent of the participants encountered minor difficulties with certain words, while the majority found it quite straightforward to choose the correct answers. CONCLUSIONS: The WORQ-A is an effective, consistent, and very easy to administer questionnaire to assess the work-related functions assumed in our study context and the individualities of the sample.

14.
Sci Rep ; 14(1): 5304, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438398

ABSTRACT

High temperatures (HT) and drought are two major factors restricting wheat growth in the early growth stages. This study investigated the role of glutathione (GSH) amendment (0.0, 0.5, 1.0, and 2.0 mM) to soil in mitigating the adverse effect of HT (33 °C, with 25 °C as a control), water regimes (60% of field capacity and control), and their combinations. HT decreased the length, project area, surface area, volume, and forks of the root, while drought had the reverse effect. Shoot length, leaf area, leaf relative water content, and shoot and root dry matter were significantly decreased by HT and drought, and their combined impact was more noticeable. GSH significantly promoted the root system, shoot growth, and leaf relative water content. The combined treatment reduced chlorophyll a, chlorophyll b, and total chlorophyll. However, 0.5 mM GSH raised chlorophyll a, chlorophyll b, and total chlorophyll by 28.6%, 41.4%, and 32.5%, respectively, relative to 0.0 mM GSH. At combined treatment, 0.5 mM GSH decreased malondialdehyde (MDA) by 29.5% and increased soluble protein content by 24.1%. GSH meaningfully enhanced the activity of superoxide dismutase, catalase, and ascorbate peroxide in different treatments. This study suggested that GSH could protect wheat seedlings from the adverse effects of HT and/or drought stresses.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Triticum , Chlorophyll A , Seedlings , Temperature , Chlorophyll , Glutathione
15.
Adv Colloid Interface Sci ; 324: 103093, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38306848

ABSTRACT

With the increasing popularity of photocatalytic technology and the highly growing issues of energy scarcity and environmental pollution, there is an increasing interest in extremely efficient photocatalytic systems. The widespread immense attention and applicability of Nb2O5 photocatalysts can be attributed to their multiple benefits, including strong redox potentials, non-toxicity, earth abundance, corrosion resistance, and efficient thermal and chemical stability. However, the large-scale application of Nb2O5 is currently impeded by the barriers of rapid recombination loss of photo-activated electron/hole pairs and the inadequacy of visible light absorption. To overcome these constraints, plentiful design strategies have been directed at modulating the morphology, electronic band structure, and optical properties of Nb2O5. The current review offers an extensive analysis of Nb2O5-based photocatalysts, with a particular emphasis on crystallography, synthetic methods, design strategies, and photocatalytic mechanisms. Finally, an outline of future research directions and challenges in developing Nb2O5-based materials with excellent photocatalytic performance is presented.

16.
Int J Biol Macromol ; 263(Pt 2): 130211, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423902

ABSTRACT

Nanocatalysts are vital in several domains, such as chemical processes, energy generation, energy preservation, and environmental pollution mitigation. An experimental study was conducted at room temperature to evaluate the catalytic activity of the new gelatin-chitosan hydrogel/CuO/Fe3O4 nanocomposite in the asymmetric Hantzsch reaction. All components of the nanocomposite exhibit a synergistic effect as a Lewis acid, promote the reaction. Dimedone, ammonium acetate, ethyl acetoacetate, and other substituted aldehydes were used to synthesize diverse polyhydroquinoline derivatives. The nanocomposite exhibited exceptional efficacy (over 90 %) and durability (retaining 80 % of its original capacity after 5 cycles) as a catalyst in the one-pot asymmetric synthesis of polyhydroquinoline derivatives. Also, turnover numbers (TON) and turnover frequency (TOF) have been checked for catalyst (TON and TOF = 50,261 and 100,524 h-1) and products. The experiment demonstrated several benefits, such as exceptional product efficacy, rapid reaction time, functioning at ambient temperature without specific requirements, and effortless separation by the use of an external magnet after the reaction is finished. The results suggest the development of a magnetic nanocatalyst with exceptional performance. The composition of the Ge-CS hydrogel/CuO/Fe3O4 nanocomposite was thoroughly analyzed using several methods including FT-IR, XRD, FE-SEM, EDX, VSM, BET, and TGA. These analyses yielded useful information into the composition and characteristics of the nanocomposite, hence further enhancing the knowledge of its possible uses.


Subject(s)
Chitosan , Nanocomposites , Nanoparticles , Chitosan/chemistry , Copper/chemistry , Gelatin , Spectroscopy, Fourier Transform Infrared , Hydrogels , Magnetic Phenomena , Oxides , Nanocomposites/chemistry
17.
Saudi J Biol Sci ; 31(2): 103916, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38223131

ABSTRACT

B-cell lymphoma/leukemia gene-2 (Bcl-2) is the primary proto-oncogene that has been shown to work by preventing apoptosis/programmed cell death. Bcl-2 combines a variety of cell-generated signals associated to the survival and death of cells. In glioma, lung, and breast cancer, Bcl-2 over-expression has been linked to an increase in invasion and migration. Many treatment regimens that target Bcl2 have been established and approved, and thus increasing the survival rates of the patients. The primary goal of this research was to recognize new therapeutic compounds that target Bcl2 and assess Bcl2 expression pattern in BC patients. We used various bioinformatic tools as well as several in vitro assays to look out the expression and inhibition of Bcl2 in BC. Our study depicted that Bcl2 had a strong connection with tumour stroma, notably with suppressor cells originating from myeloid tissues. Moreover, in vitro and in silico research identified Paclitaxel as a promising natural substance that targets Bcl2. Overall, this work shows that Bcl2 overexpression accelerates the development of BC, and that targeting Bcl2 in combination with other drugs will dramatically improve BC patient's response to treatment and prevent the emergence of drug resistance.

18.
Front Public Health ; 11: 1287223, 2023.
Article in English | MEDLINE | ID: mdl-38098834

ABSTRACT

Background: Osteoporosis, characterized by reduced bone mass and micro-architectural deterioration, poses a significant public health concern due to increased fracture susceptibility. Beyond bone health, this cross-sectional study aimed to assess and compare lower extremity proprioception and postural stability in individuals with and without osteoporosis and to explore their correlation within the osteoporosis group. Method: In this prospective cross-sectional study, 80 participants were divided into two groups: osteoporosis (n = 40) and control (n = 40). The demographic characteristics and clinical parameters of the participants were as follows: Age (years) - Osteoporosis group: 65.04 ± 4.33, Control group: 65.24 ± 4.63; Sex (%) - Osteoporosis group: Male 30%, Female 70%; Control group: Male 30%, Female 70%; Body mass index (kg/m2) - Osteoporosis group: 23.7 ± 3.2, Control group: 24.5 ± 4.6; T-score (Lumbar) - Osteoporosis group: -2.86 ± 1.23, Control group: 0.27 ± 0.58; T-score (hip) - Osteoporosis group: -2.28 ± 0.79, Control group: 0.68 ± 0.86. Joint Position Sense (JPS) at the hip, knee, and ankle was assessed using a digital inclinometer, and postural stability was measured using computerized force platforms. Result: Osteoporosis participants exhibited higher errors in hip (5.63° vs. 2.36°), knee (4.86° vs. 1.98°), and ankle (4.46° vs. 2.02°) JPS compared to controls. Postural stability measures showed increased anterior-posterior sway (10.86 mm vs. 3.98 mm), medial-lateral sway (8.67 mm vs. 2.89 mm), and ellipse area (966.88 mm2 vs. 446.19 mm2) in osteoporosis participants. Furthermore, correlation analyses within the osteoporosis group unveiled significant positive associations between lower extremity proprioception and postural stability. Specifically, hip JPS exhibited a strong positive correlation with anterior-posterior sway (r = 0.493, p = 0.003), medial-lateral sway (r = 0.485, p = 0.003), and ellipse area (r = 0.496, p < 0.001). Knee JPS displayed a moderate positive correlation with anterior-posterior sway (r = 0.397, p = 0.012), medial-lateral sway (r = 0.337, p = 0.032), and ellipse area (r = 0.378, p < 0.001). Similarly, ankle JPS showed a moderate positive correlation with anterior-posterior sway (r = 0.373, p = 0.023), medial-lateral sway (r = 0.308, p = 0.045), and ellipse area (r = 0.368, p = 0.021). Conclusion: These findings underscore the interplay between proprioceptive deficits, compromised postural stability, and osteoporosis, emphasizing the need for targeted interventions to improve fall prevention strategies and enhance the quality of life for individuals with osteoporosis.


Subject(s)
Osteoporosis , Postural Balance , Humans , Male , Female , Aged , Cross-Sectional Studies , Prospective Studies , Quality of Life , Proprioception , Lower Extremity
19.
bioRxiv ; 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37961306

ABSTRACT

Coronary artery disease (CAD) is a leading cause of death in women. Although exercise mitigates CAD, the mechanisms by which exercise impacts epicardial adipose tissue (EAT) are unknown. We hypothesized that exercise promotes an anti-inflammatory microenvironment in EAT from female pigs. Yucatan pigs (n=7) were assigned to sedentary (Sed) or exercise (Ex) treatments and coronary arteries were occluded (O) with an ameroid to mimic CAD or remained non-occluded (N). EAT was collected for bulk and single nucleus transcriptomic sequencing (snRNA-seq). Exercise upregulated G-protein coupled receptor, S100 family, and FAK pathways and downregulated the coagulation pathway. Exercise increased the interaction between immune, endothelial, and mesenchymal cells in the insulin-like growth factor pathway and between endothelial and other cell types in the platelet endothelial cell adhesion molecule 1 pathway. Sub-clustering revealed nine cell types in EAT with fibroblast and macrophage populations predominant in O-Ex EAT and T cell population predominant in N-Ex EAT. Coronary occlusion impacted the largest number of genes in T and endothelial cells. Genes related to fatty acid metabolism were the most highly upregulated in non-immune cells from O-Ex EAT. Sub-clustering of endothelial cells revealed that N-Ex EAT separated from other treatments. In conclusion, aerobic exercise increased interaction amongst immune and mesenchymal and endothelial cells in female EAT. Exercise was minimally effective at reversing alterations in gene expression in endothelial and mesenchymal cells in EAT surrounding occluded arteries. These findings lay the foundation for future work focused on the impact of exercise on cell types in EAT.

20.
Future Med Chem ; 15(23): 2181-2194, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37997685

ABSTRACT

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn's disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (1H NMR, Fourier transform IR, 13C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC50 of 0.15 ± 0.24 and 1.14 ± 0.11 µM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.


Subject(s)
DNA Gyrase , Norfloxacin , Molecular Docking Simulation , Norfloxacin/pharmacology , DNA Gyrase/metabolism , Urease/chemistry , Urease/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Structure-Activity Relationship , Molecular Structure
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