In this paper, we present a new fractional epidemiological model on a heterogeneous network to investigate Middle East respiratory syndrome (MERS-CoV), which is caused by a virus in the coronavirus ...family. We also consider the development of equations for the camel population, given that it is the primary animal source of the virus, as well as direct human interaction with this population. The model is configured in an SIS form for both the human population and the camel population. We study the equilibrium positions of the system and the conditions for the existence of each of them, as well as the local stability of each equilibrium position. Then, we provide some numerical examples that compare real data and numerical results.
A fractional-order predator–prey biological economic system with Holling type II functional response is proposed. Local stability and Hopf bifurcation of predator–prey systems have been investigated ...in both commensurate and incommensurate fractional-order systems. We explore how the economic profit and fractional orders influence the local stability and Hopf bifurcation for the fractional-order predator–prey system. For an incommensurate system, we propose a new theory for the existence of Hopf bifurcation when the fractional orders are considered as bifurcation parameters. Several numerical examples are demonstrated to validate the theoretical results.
Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of ...adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety ...and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody.
Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25–75 mg p.o. twice a day; continuous or intermittent), savolitinib (600–800 mg p.o. once a day), or durvalumab (3–10 mg/kg intravenous every 2 weeks).
At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm—diarrhea (75%), rash (58%), nausea (47%); savolitinib arm—nausea (67%), rash (56%), vomiting (50%); durvalumab arm—rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively.
Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated.
NCT02143466.
•Patients with advanced EGFR-mutant NSCLC received osimertinib 80 mg combined with selumetinib, savolitinib or durvalumab.•Feasible dosing strategies were identified for osimertinib plus selumetinib or savolitinib.•Osimertinib plus durvalumab was not feasible due to increased reporting of interstitial lung disease.•Responses were seen in all treatment arms, warranting further analysis of the feasible combinations identified.•Osimertinib-based combinations represent a compelling approach now being investigated broadly to further improve outcomes.
In this paper we are concerned with the fractional-order predator–prey model and the fractional-order rabies model. Existence and uniqueness of solutions are proved. The stability of equilibrium ...points are studied. Numerical solutions of these models are given. An example is given where the equilibrium point is a centre for the integer order system but locally asymptotically stable for its fractional-order counterpart.
As is well known the novel coronavirus (COVID-19) is a zoonotic virus and our model is concerned with the effect of the zoonotic source of the coronavirus during the outbreak in China. We present a ...SEIS complex network epidemic model for the novel coronavirus. Our model is presented in fractional form and with varying population. The steady states and the basic reproductive number are calculated. We also present some numerical examples and the sensitivity analysis of the basic reproductive number for the parameters.
Background and Purpose
Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and ...the involved molecular mechanisms.
Experimental Approach
Fifty‐two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 β‐hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8‐hydroxy‐2′‐deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors‐class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl‐2 and its associated X protein and nuclear factor kappa‐light‐chain‐enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR‐34a expression was quantified by quantitative reverse transcription‐polymerase chain reaction.
Key Results
The varicocele induced testicular histological injury, enhanced oxidative stress, P53‐mediated apoptosis, DNA damage and increased testicular miR‐34a expression paralleled with down‐regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti‐apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR‐34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele.
Conclusion and Implications
Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.
This study investigated the potential effect of adrenomedullin (ADM) on metabolic and endocrinal dysfunctions in experimentally induced polycystic ovary. Twenty‐four female Wistar rats were allocated ...into three groups: control; polycystic ovary syndrome (PCOS) in which PCOS was induced by letrozole, orally in a dose of 1 mg/kg once daily for 3 weeks; and ADM group in which ADM was injected intraperitonally in a dose of 3.5/μg/twice daily for 4 weeks. At the end of the experimental period, the serum sex hormone profile, ADM, fasting glucose, insulin, homeostatic model assessment of insulin resistance, and lipid parameters were determined. Ovarian tissue homogenates were used to determine malondialdehyde, total antioxidant capacity, glutathione peroxidase activity, tumor necrosis factor α, interleukin 6, B cell lymphoma‐2 (Bcl‐2), and Bcl‐2 associated X protein. The profibrotic growth factors, including transforming growth factor β1 and connective tissue growth factor, were determined; and also, the relative gene expression of endoplasmic reticulum (ER) stress, including (Xbox‐binding protein‐1 XBP‐1, activating transcription factor 6 ATF6, and homologous protein CHOP), serine/threonine kinase 1 (Akt1), phosphatidylinositol 3‐kinase (PI3K), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) were determined. Finally, histopathological analysis of the ovaries was evaluated. PCOS group exhibited increased ER stress, suppressing of PI3K/Akt1 and PPAR‐γ pathways, imbalance of sex hormonal profile, hyperglycemia, insulin resistance, dyslipidemia, increased profibrotic factors, and abnormal ovarian histopathological picture, while ADM treatment alleviated these disturbances occurring in the PCOS model. We concluded that ADM mitigated PCOS via attenuating the ER stress, in addition to activation of PI3K/Akt1 and PPAR‐γ pathways, its antioxidant, anti‐inflammatory, antiapoptotic, and antifibrotic properties.
This graph showed that letrozole polycystic ovary syndrome (PCOS) via multiple pathogenesis mechanisms, including hyperandrogenemia, hyperglycemia, hyperinsulinemia, dyslipidemia, and oxidative stress. All these mentioned disturbances led to insulin resistance (IR). Also, letrozole increased the production of proinflammatory cytokines, apoptosis, and stimulated profibrotic factors as transforming growth factor β1 (TGF‐β1) and connective tissue growth factor (CTGF). All these aforementioned disturbances increased endoplasmic reticulum (ER) stress, which predisposed to PCOS. However, ADM improved PCOS manifestations via suppression of ER stress and via stimulation of serine/threonine kinase 1 (Akt1), phosphatidylinositol 3‐kinase (PI3K), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) pathways with subsequent inhibition of ER stress.
This study purposed to examine the prospective curative role of lipoxin A4 (LXA4) in induced gastric ulcer in rats and explore the possible involvement of mitochondrial dynamics signaling pathway. ...Forty‐eight male Wistar rats were divided into four groups: control, indomethacin (IND), IND + omeprazole (IND + Omez), and IND+ LXA4 groups. At the end of the experiment, the gastric pH, gastric fluid volume, total gastric acidity, ulcer index, and curative index were estimated. The gene expression of mitochondrial related protein 1 and mitofusin 2 were determined. In addition, some mitochondrial parameters include mitochondrial transmembrane potential, complex‐I activity and reactive oxygen species were measured. Also, some gastric biochemical parameters, histopathological, and immunohistochemical analyses of the gastric mucosa were determined. We found that IND induced gastric ulcer, as manifested by the biochemical, histopathological, and immunohistochemical analyses. Both Omez and LXA4 treatment for 15 days alleviated the IND‐induced gastric ulcer as explored by ameliorating the biochemical, histopathological, and immunohistochemical findings. We concluded that LXA4 mitigated the IND‐induced gastric ulcer via improving the mitochondrial dynamic imbalance and mitochondrial dysfunction, in addition to its anti‐apoptotic, anti‐inflammatory, and antioxidant properties.
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