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1.
Sci Rep ; 14(1): 16237, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004673

ABSTRACT

This paper presents new relativistic composite polytropic models for compact stars by simultaneously solving Einstein field equations with the polytropic state equation to simulate the spherically symmetric, static matter distribution. Using a non-uniform polytropic index, we get the Tolman-Oppenheimer-Volkoff equation for the relativistic composite polytrope (CTOV). To analyze the star's structure, we numerically solve the CTOV equation and compute the Emden and mass functions for various relativistic parameters and polytropic indices appropriate for neutron stars. The calculation results show that, as the relativistic parameter approaches zero, we recover the well-known Lane-Emden equation from the Newtonian theory of polytropic stars; thus, testing the computational code by comparing composite Newtonian models to those in the literature yields good agreement. We compute composite relativistic models for the neutron star candidates Cen X-3, SAXJ1808.4-3658, and PSR J1614-22304. We compare the findings with various existing models in the literature. Based on the accepted models for PSR J1614-22304 and Cen X-3, the star's core radius is predicted to be between 50 and 60% percent of its total radius, while we found that the radius of the core of star SAXJ1808.4-3658 is around 30% of the total radius. Our findings show that the neutron star structure may be approximated by a composite relativistic polytrope, resulting in masses and radii that are quite consistent with observation.

2.
iScience ; 27(6): 110138, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38974469

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron breakthrough infection (BTI) induced better protection than triple vaccination. To address the underlying immunological mechanisms, we studied antibody and T cell response dynamics during vaccination and after BTI. Each vaccination significantly increased peak neutralization titers with simultaneous increases in circulating spike-specific T cell frequencies. Neutralization titers significantly associated with a reduced hazard rate for SARS-CoV-2 infection. Yet, 97% of triple vaccinees became SARS-CoV-2 infected. BTI further boosted neutralization magnitude and breadth, broadened virus-specific T cell responses to non-vaccine-encoded antigens, and protected with an efficiency of 88% from further infections by December 2022. This effect was then assessed by utilizing mathematical modeling, which accounted for time-dependent infection risk, the antibody, and T cell concentration at any time point after BTI. Our findings suggest that cross-variant protective hybrid immunity induced by vaccination and BTI was an important contributor to the reduced virus transmission observed in Bavaria in late 2022 and thereafter.

3.
Chem Biodivers ; : e202400831, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005105

ABSTRACT

5-(Cyanomethyl)-3-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-1H-pyrazole-4-carbonitrile (3) is used as a key for the synthesis of arylidenes 5a-fvia its reaction with some aldehydes 4a-f. 5-[(5,5-Dimethyl-3-oxocyclohex-1-en-1-yl)amino]-3-(2-imino-2H-chromen-3-yl)-1H-pyrazole-4-carbonitrile (7) was synthesized via the reaction of compound (3) with 2-hydroxybenzaldehyde in EtOH/piperidine. The target compounds were tested against cotton leafworm larvae in their second and fourth instar. The available data demonstrated that the LC50 values for commercial phenylpyrazole were 3.37 mg/L and 4.55 mg/L for the most affected synthesized compound, 5b. The chemical structure of compound 5b has two cyano moieties, a pyrazole ring and a chlorophenyl, which may be increasing it efficiency. Evaluation of the latent effects of the examined synthesized compounds on various biological parameters, including adult longevity, pupal weight, proportion of normal, deformed pupae, adult emergency, fecundity, and egg hatchability, was done in an additional effort to slightly improve insecticidal compounds. Twelve synthesized compounds were subjected to a molecular docking analysis against glutamate-activated chloride channels. Twelve artificial compounds with the PDB ID of 4COF were subjected to a molecular docking study against the gamma-aminobutyric acid receptor (GABA).

4.
Anal Chim Acta ; 1317: 342904, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39030024

ABSTRACT

BACKGROUND: Resveratrol, a natural polyphenol compound used as an ingredient in dietary supplements, and pharmaceuticals, has gained significant attention due to its potential health benefits. However, the accurate and sensitive determination of resveratrol in complex matrices remains a challenge. In this study, we propose the utilization of bimetallic porous Mn/Co oxide nanosheets (MnCoO-NSs) as catalysts for the colorimetric determination of resveratrol. RESULTS: The bimetallic porous MnCoO-NSs were prepared through a facile one-stone-two-birds strategy. These nanosheets exhibited superior oxidase-mimicking activity, as evidenced by the catalytic oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB), producing a blue-colored oxTMB species with a prominent absorbance peak at 655 nm. The catalytic activity was promoted through the production of superoxide anion (O2•-), which enhanced the affinity of MnCoO-NSs to the TMB molecules. Upon the addition of resveratrol, the oxidation process was inhibited, resulting in rapid fading of the blue color. This colorimetric sensing platform exhibited a linear response to resveratrol concentrations over the range of 2.2-87.6 µM, with a limit of detection of 0.210 µM. The method was further applied for the determination of resveratrol in different matrices including biological fluids, pharmaceuticals, and environmental water. SIGNIFICANCE: The utilization of these MnCoO-NSs offers a simple and cost-effective alternative to conventional analytical techniques for the determination of resveratrol. Their high sensitivity, selectivity, and stability enable accurate measurements of resveratrol in various complex matrices. This research has implications in areas such as pharmaceutical analysis, biomedical research, and environmental analysis, where the reliable determination of resveratrol is crucial for assessing its therapeutic potential and ensuring product quality.


Subject(s)
Cobalt , Colorimetry , Oxides , Resveratrol , Resveratrol/chemistry , Resveratrol/metabolism , Resveratrol/analysis , Colorimetry/methods , Cobalt/chemistry , Oxides/chemistry , Porosity , Nanostructures/chemistry , Oxidoreductases/metabolism , Oxidoreductases/chemistry , Limit of Detection , Manganese Compounds/chemistry , Humans , Oxidation-Reduction , Catalysis , Manganese/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/metabolism , Biomimetic Materials/chemistry
5.
Sci Rep ; 14(1): 16660, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030233

ABSTRACT

The fibrous wastes generated from the mills of textile production can be recycled and converted into high add-values products to be implemented in several applications. The current study aimed to employ commercial free cellulase enzyme to partially hydrolyze (activate) the polyester cotton blended (PET/C) fibrous wastes by creation functional groups such as OH and COOH on their surfaces. The activated fibrous wastes were then modified by coating with ZnO nanoparticles (ZnO-NPs) biosynthesized by actinobacterial cultures free supernatant. The isolate was identified as Streptomyces pseudogriseolus with accession number of OR574241. The conditions that influence the actino-synthesis of ZnO-NPs were optimized and the product was characterized using spectroscopic vision, FTIR, XRD, TEM and SEM. The characteristic ZnO peaks were obviously observed by EDX analysis with 0.38 and 0.75% (wt%), respectively. TEM analyses proved the nanoscale of ZnO-NPs (5-15 nm) which was followed by cytotoxic evaluation for the produced NPs. Fortunately, the tested actino-ZnO-NPs didn't have any cytotoxicity against human normal fibroblast cell line (BJ1), which means that the product can be safely used in a direct-contact with human skin. The treated PET/C blended waste fabrics coated with ZnO-NPs showed high antimicrobial activity and ultraviolet protection values after functionalization by cellulase. EDX analysis demonstrates the presence of Zn peaks on the coated fabrics compared with their absence in blank and control samples, while SEM images showed the formation of a thin layer of ZnO-NPs on the fabric surface. The obtained smart textile can be applied several needed sectors.


Subject(s)
Textiles , Zinc Oxide , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Humans , Metal Nanoparticles/chemistry , Streptomyces/metabolism , Cell Line , Industrial Waste , Fibroblasts/drug effects , Fibroblasts/metabolism
6.
Sci Rep ; 14(1): 16415, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014030

ABSTRACT

Power quality is a crucial determinant for integrating wind energy into the electrical grid. This integration necessitates compliance with certain standards and levels. This study presents cascadedfuzzy power control (CFPC) for a variable-speed multi-rotor wind turbine (MRWT) system. Fuzzy logic is a type of smart control system already recognized for its robustness, making it highly suited and reliable for generating electrical energy from the wind. Therefore, the CFPC technique is proposed in this work to control the doubly-fed induction generator (DFIG)-based MRWT system. This proposed strategy is applied to the rotor side converter of a DFIG to improve the current/power quality. The proposed control has the advantage of being model-independent, as it relies on empirical knowledge rather than the specific characteristics of the DFIG or turbine. Moreover, the proposed control system is characterized by its simplicity, high performance, robustness, and ease of application. The implementation of CFPC management for 1.5 MW DFIG-MRWT was carried out in MATLAB environment considering a variable wind speed. The obtained results were compared with the direct power control (DPC) technique based on proportional-integral (PI) controllers (DPC-PI), highlighting that the CFPC technique reduced total harmonic distortion by high ratios in the three tests performed (25%, 30.18%, and 47.22%). The proposed CFPC technique reduced the response time of reactive power in all tests by ratios estimated at 83.76%, 65.02%, and 91.42% compared to the DPC-PI strategy. Also, the active power ripples were reduced by satisfactory proportions (37.50%, 32.20%, and 38.46%) compared to the DPC-PI strategy. The steady-state error value of reactive power in the tests was low when using the CFPC technique by 86.60%, 57.33%, and 72.26%, which indicates the effectiveness and efficiency of the proposed CFPC technique in improving the characteristics of the system. Thus this control can be relied upon in the future.

7.
Clin Pharmacol Ther ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847591

ABSTRACT

Glucagon was discovered about a hundred years ago and its role in health and disease is under continuous investigation. Glucagon is a counter regulatory hormone secreted by alpha cells of the pancreas in response to multiple stimuli. Although some of glucagon's actions and its clinical application have been described, clinical experience with glucagon has been historically overshadowed by that of insulin. To date, the role of glucagon's actions in pharmacotherapy has been under explored. Glucagon plays a considerable role as a hormonal regulator via its known actions on the liver. The rise in obesity and diabetes mellitus prevalence is bringing focus to glucagon's known physiological roles and possible clinical applications. Six glucagon products and a glucagon analog are approved for use in the United States. Clinical pharmacology studies provide crucial support of glucagon's actions as evident from comprehensive pharmacokinetics and pharmacodynamics evaluations in humans. Here, we briefly describe the established physiological role of glucagon in humans and its known relationship with disease. We later summarize the clinical pharmacology of available glucagon products with different routes of administration.

8.
Article in English | MEDLINE | ID: mdl-38916819

ABSTRACT

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

9.
NPJ Breast Cancer ; 10(1): 44, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38866818

ABSTRACT

Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. Females ages 18+ with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. Among 4459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.

10.
Surg Obes Relat Dis ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38937216

ABSTRACT

BACKGROUND: Studies were conducted to investigate the outcomes of bariatric surgery (BS) among inflammatory bowel disease (IBD) patients. OBJECTIVES: We aimed to analyze previous literature, comparing the outcomes of BS between IBD and non-IBD patients. SETTING: Not applicable. METHODS: PubMed, Scopus, and Web of Science were searched on 25/9/2023 for comparative studies on outcomes of BS in IBD patients. RevMan Software v5.4 was used to conduct the analysis. RESULTS: Our analysis revealed an insignificant difference in the change of body mass index (BMI) at 1-year post-BS between IBD and non-IBD patients. IBD patients had a higher risk of acute renal failure, hemorrhage, and readmission following BS (RR: 2.16, 95% CI: 1.55-3, RR: 1.57, 95% CI: 1.22-2.04, RR: 1.56, 95% CI: 1.17-2.08, respectively). No significant difference was observed between both groups regarding wounds, leak/intra-abdominal infection, thromboembolic complications, and bowel obstruction. A higher incidence of postoperative complications was seen among IBD patients undergoing RYGB compared with SG (RR: 2.21, 95% CI: 1.43-3.41). There was a significant decline in steroid use following BS in IBD patients (RR: .67, 95% CI: .53-.84). Comparison between UC and Crohn's disease (CD) revealed insignificant differences in treatment escalation or de-escalation. Both IBD and non-IBD patients had similar lengths of hospitalization. CONCLUSIONS: BS is equally effective in IBD and non-IBD patients in terms of weight loss at 1-year follow-up. Nevertheless, IBD patients are at a higher risk of postoperative complications, micronutrient deficiency, and readmission. Both UC and CD reported a decline in steroid use following surgery without a preferential advantage to a particular IBD sub-type.

11.
Front Immunol ; 15: 1277074, 2024.
Article in English | MEDLINE | ID: mdl-38915405

ABSTRACT

Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, ß-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and ß-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.


Subject(s)
Garlic , Garlic/chemistry , Humans , Animals , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Phytochemicals/therapeutic use , Phytochemicals/pharmacology , Sulfinic Acids/therapeutic use , Sulfinic Acids/pharmacology , Disulfides
12.
Article in English | MEDLINE | ID: mdl-38922404

ABSTRACT

Cephalomedullary nailing for unstable proximal femoral fractures is widely utilized, especially for geriatric osteoporotic fractures. There are two starting points for entry, namely trochanteric tip entry and pyriformis fossa entry, both have advantages and disadvantages, the tip of the greater trochanter seems that it is not the ideal starting point for trochanteric entry nails, the study presents the foothill entry point as a reproducible, technically feasible entry point to overcome the shortcoming of both standard starting points, and it could be easy executed with clear intraoperative fluoroscopic landmarks and lead to appropriate nail position without intraoperative complications.

13.
Ann Surg Oncol ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872045

ABSTRACT

PURPOSE: This study was designed to characterize features of rapid relapse TNBC (rrTNBC), an aggressive, poor prognosis breast cancer subset using the National Cancer Database (NCDB). METHODS: Patients diagnosed with TNBC between 2010 and 2019 within NCDB were included in analyses. rrTNBC was defined as all-cause mortality ≤24 months from diagnosis. Patient demographic, tumor, and treatment association with rrTNBC were evaluated in univariate, bivariate analyses, and multiple logistic regression models. Two-part models are used to compare receipt of treatment (i.e., receipt of both chemotherapy and breast surgery) versus not in its relationship with rrTNBC. RESULTS: Overall, 14.5% of patients were categorized as rrTNBC. Age older than 75 years (-41.3%), Black race (-1.4%), Medicare (-2.6%), and Charlson-Deyo score ≥2 (-4.9%) were associated with a lower probability of receiving both chemotherapy and breast surgery. Not receiving both treatments (vs. receiving both chemotherapy and breast surgery) was associated with a two-to-three-fold higher probability of rrTNBC among patients aged older than 75 years (16.6% vs. 6%), having Medicare (3.6% vs. 1.6%), and Charlson-Deyo score ≥2 (16.6% vs. 5.9%). CONCLUSIONS: Age, insurance, and comorbidity were related to a lower likelihood of treatment; yet receiving treatment reduced the risk of rrTNBC threefold for each. These findings might be valuable to inform clinical care delivery, as well as future research that examines treatment protocols among diverse patients.

14.
Adv Sci (Weinh) ; : e2403516, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38868948

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) is hallmarked by hepatic steatosis, cell injury, inflammation, and fibrosis. This study elaborates on a multicellular biochip-based liver sinusoid model to mimic MASLD pathomechanisms and investigate the therapeutic effects of drug candidates lanifibranor and resmetirom. Mouse liver primary hepatocytes, hepatic stellate cells, Kupffer cells, and endothelial cells are seeded in a dual-chamber biocompatible liver-on-a-chip (LoC). The LoC is then perfused with circulating immune cells (CICs). Acetaminophen (APAP) and free fatty acids (FFAs) treatment recapitulate acute drug-induced liver injury and MASLD, respectively. As a benchmark for the LoC, multiplex immunofluorescence on livers from APAP-injected and dietary MASLD-induced mice reveals characteristic changes on parenchymal and immune cell populations. APAP exposure induces cell death in the LoC, and increased inflammatory cytokine levels in the circulating perfusate. Under FFA stimulation, lipid accumulation, cellular damage, inflammatory secretome, and fibrogenesis are increased in the LoC, reflecting MASLD. Both injury conditions potentiate CIC migration from the perfusate to the LoC cellular layers. Lanifibranor prevents the onset of inflammation, while resmetirom decreases lipid accumulation in hepatocytes and increases the generation of FFA metabolites in the LoC. This study demonstrates the LoC potential for functional and molecular evaluation of liver disease drug candidates.

15.
Article in English | MEDLINE | ID: mdl-38890818

ABSTRACT

This investigation was directed to examine the influence of copper oxide nanoparticles (CuO-NPs) on the hatchability traits, and chick quality of newly hatched broiler chicks. A total of 480 eggs were randomly divided into four treatment groups, each consisting of three duplicates. As a negative control (NC), the first group was not injected; the second group was injected with saline and served as a positive control (PC), the third and fourth groups were injected with 30 and 60 ppm of (CuO-NPs)/egg. Eggs were injected into the amniotic fluid on the eighteenth day of the incubation period. Results showed that the hatchability, chick yield %, yolk free-body mass (YFBM), chick length, shank length (SL), and relative weight of the heart, gizzard and intestine of day-old broiler chicks were all unaffected by the in ovo injection of CuO-NPs. The Pasgar Score was slightly improved compared to the NC and PC groups. Also, the in ovo administration of CuO-NPs (60 ppm/egg) significantly increased the intestine length. Both levels of CuO-NPs significantly increased the concentration of Cu ions in the hepatic tissue. Additionally, different levels of tissue damage were seen in the liver of the birds that were given low or high dosages of CuO-NPs. Conclusively, the in ovo injection of CuO-NPs has a good result on the appearance of the chicks (Pasgar score). However, negative effect of CuO-NPs on liver tissue may raise concerns about the potential risks of applying CuO-NPs in ovo administration.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124559, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38830331

ABSTRACT

In this work, we present a novel colorimetric sensing platform for the sensitive detection of ethamsylate (ETM) usingultrathin MnO2 nanosheets with enhancedoxidase-mimicking activity. A facile template-free hydrothermal process was applied to synthesize the MnO2 nanosheets under mild conditions. The nanosheets exhibited oxidase-mimicking activity, facilitating the conversion of TMB into the blue-colored oxTMB in the absence of H2O2. However, the presence of ETM inhibited this activity, resulting in the conversion of oxTMB back to colorless TMB and a substantial decrease in the blue color intensity. The colorimetric response exhibited a linear relationship with ETM concentration over the range of 0.5 to 10.0 µg/mL and a detection limit of 0.156 µg/mL. To further elucidate the underlying mechanism, we performed extensive characterization and kinetic experiments. The findings demonstrated that this unique property is attributed to the remarkable capacity of the MnO2 nanosheets to absorb oxygen, producing superoxide radicals (O2-). The oxidase-mimicking activity of the nanosheets was further confirmed by the reaction kinetics, following Michaelis-Menten's behavior. Moreover, the applicability of the sensing platform was assessed by determining ETM concentrations in various real samples (different pharmaceuticals, human plasma, and environmental water). The well-established platform demonstrates the prospective role that nanomaterials-based sensing platforms may play in clinical diagnostics, pharmaceutical analysis, and other relevant fields.


Subject(s)
Colorimetry , Limit of Detection , Manganese Compounds , Nanostructures , Oxides , Oxidoreductases , Colorimetry/methods , Manganese Compounds/chemistry , Oxides/chemistry , Nanostructures/chemistry , Oxidoreductases/metabolism , Oxidoreductases/chemistry , Kinetics , Hydrogen Peroxide/analysis , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Biomimetic Materials/chemistry , Benzidines/chemistry
17.
Bioorg Chem ; 150: 107574, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38936049

ABSTRACT

Mitochondrial dynamics have pillar roles in several diseases including cancer. Cancer cell survival is monitored by mitochondria which impacts several cellular functions such as cell metabolism, calcium signaling, and ROS production. The equilibrium of death and survival rate of mitochondria is important for healthy cellular processes. Whereas inhibition of mitochondrial metabolism and dynamics can have crucial regulatory decisions between cell survival and death. The steady rate of physiological flux of both mitochondrial fission and fusion is strongly related to the preservation of cellular bioenergetics. Dysregulation of mitochondrial dynamics including fission and fusion is a critical machinery in cells accompanied by crosstalk in cancer progression and resistance. Many cancer cells express high levels of Drp-1 to induce cancer cell invasion, metastasis and chemoresistance including breast cancer, liver cancer, pancreatic cancer, and colon cancer. Targeting Drp-1 by inhibitors such as Midivi-1 helps to enhance the responsiveness of cancer cells towards chemotherapy. The review showed Drp-1 linked processes such as mitochondrial dynamics and relationship with cancer, invasion, and chemoresistance along with computational assessing of all publicly available Drp-1 inhibitors. Drp1-IN-1, Dynole 34-2, trimethyloctadecylammonium bromide, and Schaftoside showed potential inhibitory effects on Drp-1 as compared to standard Mdivi- 1. This emerging approach may have extensive strength in the context of cancer development and chemoresistance and further work is needed to aid in more effective cancer management.


Subject(s)
Antineoplastic Agents , Drug Resistance, Neoplasm , Dynamins , Neoplasms , Humans , Dynamins/antagonists & inhibitors , Dynamins/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Drug Resistance, Neoplasm/drug effects , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Mitochondrial Dynamics/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Molecular Structure , Animals , Quinazolinones/pharmacology , Quinazolinones/chemistry , Quinazolinones/chemical synthesis
18.
Neurol Clin Pract ; 14(3): e200277, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38737513

ABSTRACT

Background and Objectives: To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs. Methods: Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study). Results: Six patients carrying different mutations in different genes of CMSs were studied. They had different pathophysiologic profiles (slow or fast channel syndromes, low expressor of receptor). Their therapeutic management was based on innovative drugs, normally indicated in other, non-neurological pathologies. Their outcome was toward a clear clinical improvement. Discussion: This work relates the interest of proposing treatments (outside of Pyridostigmine) in the management of CMSs. These therapies can greatly modify the prognosis of patients suffering from this orphan disease. Classification of Evidence: This study provides Class IV evidence that for patients with congenital myasthenic syndromes, some innovative treatments are effective.

19.
PLoS One ; 19(5): e0303863, 2024.
Article in English | MEDLINE | ID: mdl-38781241

ABSTRACT

Type 1 diabetes (T1D)-associated hyperglycemia develops, in part, from loss of insulin-secreting beta cells. The degree of glycemic dysregulation and the age at onset of disease can serve as indicators of the aggressiveness of the disease. Tracking blood glucose levels in prediabetic mice may demonstrate the onset of diabetes and, along with animal age, also presage disease severity. In this study, an analysis of blood glucose levels obtained from female NOD mice starting at 4 weeks until diabetes onset was undertaken. New onset diabetic mice were orally vaccinated with a Salmonella-based vaccine towards T1D-associated preproinsulin combined with TGFß and IL10 along with anti-CD3 antibody. Blood glucose levels were obtained before and after development of disease and vaccination. Animals were classified as acute disease if hyperglycemia was confirmed at a young age, while other animals were classified as progressive disease. The effectiveness of the oral T1D vaccine was greater in mice with progressive disease that had less glucose excursion compared to acute disease mice. Overall, the Salmonella-based vaccine reversed disease in 60% of the diabetic mice due, in part, to lessening of islet inflammation, improving residual beta cell health, and promoting tolerance. In summary, the age of disease onset and severity of glucose dysregulation in NOD mice predicted response to vaccine therapy. This suggests a similar disease categorization in the clinic may predict therapeutic response.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 1 , Mice, Inbred NOD , Animals , Female , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/microbiology , Mice , Administration, Oral , Blood Glucose/metabolism , Salmonella Vaccines/immunology , Salmonella Vaccines/administration & dosage , Salmonella/immunology , Insulin/immunology , Disease Progression , Acute Disease , Protein Precursors
20.
Sci Rep ; 14(1): 11149, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750110

ABSTRACT

The research aim is to clarify the effect of courtyard placement, the ratio between length and width, and courtyard orientation on energy consumption in residential buildings in hot and dry climates, to seek planning and designing alternatives for new cities and new residential complexes that are consistent with the environment and climate and save the consumption of energy used in the buildings. The research method was conducted through Design Builder software for simulation purposes. The reference model with the 157.25 m2 which accommodates a central square courtyard measuring 5 m × 5 m, on a residential building model in the New Valley Governorate of Kharga City, Egypt. The courtyard simulation is aimed to determine Less energy consumption inside the different case studies, in 9 courtyard placements The studied alternatives for Courtyard Placement, are (the center of the building, sub facades, and main facades). The different ratios are (1:1, 1.25:1, 1.5:1-1.75:1, 2:1, 2.25:1, 2.5-1). The longitudinal axis of the Courtyard has been oriented to the east-west direction for all placements, and north-south direction for all placements. Also, (orientation angle is Zero), it offered the percentages of better and worst cases in each position of the courtyard. The research findings suggest that the best Placement of the Courtyard that achieved the highest rate of saving of energy consumed inside the used building model was at the southwestern façade, with a saving rate of 18.73%. Then, the Placement of the Courtyard at the northwestern and southeastern facades with a saving rate of 17.91%, with a length-to-width ratio (2.5:1) if the longitudinal axis of the Courtyard is oriented in the north-south direction, Through the study, we conclude that the placement and orientation of the courtyard and its regular formation have contributed to rationalizing energy consumption in residential buildings, the study reached some important standards that could represent a methodological framework for designing contemporary residential buildings with an energy-efficient inner courtyard.

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