The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for ...the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.
This study deals with the production of natural fiber plastic composites (NFPCs) to reduce environmental pollution with agricultural and plastic waste. Where the NFPCs were prepared from waste/pure ...polyethylene (WPE) (pure polyethylene (50%)/recycled polyethylene (50%)) and modified sunflower waste via an eco-friendly and economic biological process. The sunflower fibers (SF) were treated via whole selective fungal isolate, namely, Rhizopus oryzae (acc no. OM912662) using two different incubation conditions; submerged (Sub), and solid-state fermentation (SSF) to enhance the fibers' compatibility with WPE. The treated and untreated fibers were added to WPE with various concentrations (10 and 20 wt%). The morphology and structure of fibers were characterised by a scanning electron microscope (SEM) and attenuated total reflection-Fourier transform infrared (ATR-FTIR). Furthermore, the mechanical properties, morphology, biodegradation and water vapour transmission rate (WVTR) for the prepared NFPCs were investigated. The results showed that compatibility, mechanical properties and biodegradation of NFPCs were improved by the addition of sunflower fibers treated by SSF conditions.
•Bionanocomposites were prepared as coating materials for Ras cheese.•Different ratios of TiO2 nanoparticle were used during bionanocomposite preparation.•The TiO2-NPs and bionanocomposites were ...characterized by XRD, SEM and TEM.•The obtained CS/PVA/TiO2 bionanocomposites displayed good WVTR, mechanical and barrier properties.•The cheese was kept free from surface mould growth up to 3 months by using the developed coating material.
The aim of the present study was to prepare and characterize bionanocomposite materials, and to evaluate its use in the coating of Ras cheese. The bionanocomposite materials were made from mixture of chitosan/polyvinyl alcohol with loading of titanium dioxide nanoparticles (TiO2-NPs) from (0.5–2%). The prepared nanoparticles as well as the bionanocomposites were evaluated using, XRD, SEM, TEM, FT-IR and final contact angle. Furthermore, the mechanical properties and water vapor transmission rate (WVTR) of the fabricated bionanocomposites were evaluated. The impacts of coating Ras cheese with the prepared bionanocomposite on weight losses and microbiological, chemical, and physical characteristics of the Ras cheese were assessed during ripening in comparison to the uncoated cheese. Coating of cheese decreased the weight and moisture losses but didn't affect the normal ripening changes in the microbiological, chemical and textural properties of Ras cheese. Coating cheese with film containing 2% TiO2-NPs eliminated mold growth on the cheese surface.
Heat-shock proteins are upregulated in cancer and protect several client proteins from degradation. Therefore, they contribute to tumorigenesis and cancer metastasis by reducing apoptosis and ...enhancing cell survival and proliferation. These client proteins include the estrogen receptor (ER), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), human epidermal growth factor receptor 2 (HER-2), and cytokine receptors. The diminution of the degradation of these client proteins activates different signaling pathways, such as the PI3K/Akt/NF-κB, Raf/MEK/ERK, and JAK/STAT3 pathways. These pathways contribute to hallmarks of cancer, such as self-sufficiency in growth signaling, an insensitivity to anti-growth signals, the evasion of apoptosis, persistent angiogenesis, tissue invasion and metastasis, and an unbounded capacity for replication. However, the inhibition of HSP90 activity by ganetespib is believed to be a promising strategy in the treatment of cancer because of its low adverse effects compared to other HSP90 inhibitors. Ganetespib is a potential cancer therapy that has shown promise in preclinical tests against various cancers, including lung cancer, prostate cancer, and leukemia. It has also shown strong activity toward breast cancer, non-small cell lung cancer, gastric cancer, and acute myeloid leukemia. Ganetespib has been found to cause apoptosis and growth arrest in these cancer cells, and it is being tested in phase II clinical trials as a first-line therapy for metastatic breast cancer. In this review, we will highlight the mechanism of action of ganetespib and its role in treating cancer based on recent studies.
Empagliflozin and metformin are widely used for the treatment of type 2 diabetes. These drugs showed marked anti-inflammatory effects in different animal models
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enhancing AMPK activity. Yet, the ...protective anti-inflammatory effects of their combination against ulcerative colitis have not been previously investigated. The current study aimed to explore the potential of empagliflozin/metformin combination to mitigate the DSS-induced rat colitis model. The modulating effects of empagliflozin and metformin on the AMPK/mTOR/NLRP3 axis and T cell polarization were delineated. In this study, distal colons were examined for macroscopic and microscopic pathological alterations. ELISA, qRT-PCR, and immunohistochemistry techniques were applied to detect proteins and cytokines involved in AMPK/mTOR/NLRP3 axis and T Cell polarization. Oral administration of empagliflozin (10 mg/kg/day) and metformin (200 mg/kg/day) combination alleviated colitis as revealed by the reduced disease activity index, macroscopic damage index, colon weight/length ratio, and histopathologic scoring values. Interestingly, empagliflozin/metformin combination significantly enhanced AMPK phosphorylation and depressed mTOR and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Reduced mTOR expression and reduced IL-6 levels led to a reduction in Th17 cell polarization and maintenance. Together, the current study reveals that the protective effects of empagliflozin and metformin against DSS-induced colitis are fundamentally mediated
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enhancing AMPK phosphorylation. Since adult humans with diabetes mellitus are at greater risk for developing inflammatory bowel diseases, clinical application of empagliflozin/metformin combination represents a novel therapeutic approach for treating diabetic patients with ulcerative colitis.
The cholinergic anti-inflammatory pathway (CAP) was investigated in a variety of inflammatory conditions and constitutes a valuable line in their treatment. In the current study, we investigated the ...anti-inflammatory effect of GTS-21 (GTS) as a partial selective α7 nicotinic acetylcholine receptor (α7-nAchR) agonist in diabetic cardiomyopathy model in rats. This mechanism was elaborated to study whether it could alleviate the electrocardiographic, histopathological, and molecular levels of Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway proteins. Diabetes was induced by the injection of streptozotocin (STZ) (50 mg/kg). Diabetic rats were treated with GTS (1 or 2 mg/kg/day), methyllycaconitine (MLA), a selective α7-nAchR antagonist (2 mg/kg/day) plus GTS (2 mg/kg/day), or the vehicle. All treatments were given by the intraperitoneal route. Ventricular rate and different electrocardiograph (ECG) anomalies were detected. Plasma levels of cardiac troponin T (cTnT) and creatine kinase MB (CK-MB) were measured by ELISA. Additionally, we elucidated the levels of several proteins involved in the TLR4/NF-κB pathway. Cardiac levels of TLR4 and phosphorylated protein kinase B (p-Akt) were detected by ELISA. The cardiac expression of myeloid differentiation primary response 88 (Myd88), tumor necrosis factor receptor-associated factor 6 (TRAF6), NF-κB, interleukin 1β (IL-1β), and active caspase-1 were evaluated by immunohistochemical staining. Finally, the cardiac levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. Diabetic rats showed (i) ECG signs of cardiomyopathy such as significant ST segment elevations, prolonged QRS, QT intervals, and ventricular tachycardia; (ii) increased plasma levels of cTnT and CK-MB; (iii) increased expression of cardiac TLR4; (iv) elevated immunohistochemical expression of cardiac, Myd88, TRAF6, and NF-κB; (v) diminution in the cardiac expression of p-Akt; and (vi) adaptive increases in cardiac expression of TNF-α and IL-6. These effects were ameliorated in diabetic rats treated with both doses of GTS. Pretreatment with MLA did not completely reverse the ameliorative effect of GTS on cTnT, TRAF6, TNF-α, and IL-6, thereby reinforcing the presence of possible α7-nAchR-independent mechanisms. The activation of α7-nAchR with GTS offers a promising prophylactic strategy for diabetic cardiomyopathy by attenuating the TLR4/NF-κB pathway.
Angiogenesis accelerates tissue regeneration in a variety of ischemic conditions including myocardial infarction (MI). Here we tested the hypothesis that angiogenesis induced by α7-nicotinic ...acetylcholine receptors (α7-nAChRs) mitigates histopathological, electrocardiographic, and molecular consequences of MI in rats. These profiles were evaluated in the isoprenaline (85 mg/kg/day i. p. For 2 days) MI rat model treated with or without nicotine or PHA-543613 (PHA, selective α7-nAChR agonist). Isoprenaline-insulted rats showed (i) ECG signs of MI such as significant ST-segment elevations and prolonged QT-intervals, (ii) deteriorated left ventricular histopathological scoring and elevated inflammatory cell infiltration, (iii) reduced immunohistochemical expression of cardiac CD34, a surrogate marker of capillary density, (iv) decreased cardiac expression of iNOS and α7-nAChRs, and (v) adaptive increases in cardiac HO-1 expression and plasma angiogenic markers such as vascular endothelial growth factor (VEGF) and nitric oxide (NO). These effects of isoprenaline, except cardiac iNOS and α7-nAChRs downregulation, were ameliorated in rats treated with a low dose (20 μg/kg/day s. c. For 16 days) of nicotine or PHA. We also show that concurrent α7-nAChR blockade by methyllycaconitine (MLA, 40 μg/kg/day, for 16 days) reversed the ECG, histopathological, and capillary density effects of nicotine, thereby reinforcing the advantageous cardioprotective and anti-ischemic roles of α7-nAChRs in this setting. The observed results showed promising effects on isoprenaline induced myocardial damage. In conclusion, the activation of α7-nAChRs by doses of nicotine or PHA in the microgram scale promotes neovascularization and offers a promising therapeutic strategy for MI.
Cardiovascular Pharmacology.
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Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel ...curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund’s adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat’s hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor–kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis.
Ulcerative colitis is an idiopathic disease that is widely incident worldwide. Canagliflozin, antidiabetic agent, exhibited significant anti-inflammatory effects in a variety of animal models. ...Additionally, hyaluronic acid is considered one of the key players in the tissue regeneration process. It has been proven to modulate inflammation and cellular migration, which are the main phases of wound healing. The combination of hyaluronic acid with chitosan in microsphere fabrication was anticipated to reveal a synergistic muco-adhesiveness potential with additional advantage of the chitosan penetration enhancing effect. The current study aimed to explore the potential of canagliflozin-loaded chitosan-hyaluronic acid microspheres intrarectal administration to mitigate acetic acid-induced colitis in rats. Colon tissues were examined for macroscopic and microscopic pathological changes. ELISA and qRT-PCR techniques were applied for the detection of cytokines involved in the AMPK/NF-κB/NLRP3 axis. Intrarectal administration of this formula alleviated colitis severity, which was reflected by the reduced DAI, MES, colonic weight/length ratio and histopathological scoring values. Interestingly, canagliflozin-loaded chitosan-hyaluronic acid microspheres significantly enhanced AMPK phosphorylation and depressed NF-κB and NLRP3 expression leading to a subsequent reduction in caspase-1 cleavage and the inhibition of several inflammatory cytokines, including IL-1β, and IL-18. Overall, the current study revealed that the protective effects of the formula against acetic acid-induced colitis are primarily mediated via augmenting AMPK phosphorylation and its consequences of NF-κB inactivation. Since canagliflozin is not associated with hypoglycemic effects, clinical application of canagliflozin-loaded chitosan-hyaluronic acid microspheres represent a novel therapeutic option for the treatment of patients with ulcerative colitis.
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•Canagliflozin-loaded chitosan-hyaluronic acid microspheres revealed coloprotective effects.•This formula prepared to possess mucoadhesiveness potential and penetration enhancing effect.•Rectal therapy using this formula enhanced autophagy by modulating AMPK/mTOR axis.•This preparation interfered with TLR4/NF-κB axis and inactivated NLRP3 inflammasome assembly.•This preparation exhibited antiapoptotic effect through upregulating BCL-2.
Bagasse raw materials were filled with recycled polyvinyl chloride composites via compounding and compression molding. In this research, unmodified, soda treated, and oxidized bagasse fibers were ...combined in different concentrations (5%, 10%, 15%, and 20%) with pure PVC/recycled PVC (30:70 wt). The composites surfaces were examined as well as their mechanical properties, crystallization behavior, and biodegradation properties. It was found that uniformity in the distribution of the bagasse fibers in the microstructure of the polymer composites was a major factor affecting the mechanical properties. The oxidized bagasse fiber loaded composite matrix gives the best mechanical and biodegradation properties compared with the untreated and soda treated bagasse fibers. In addition to increasing modulus and tensile strength, fiber loading also reduced hardness. X‐ray diffraction investigation illustrated that introducing fiber to a p‐ PVC/r‐PVC matrix did not affect characteristic peak positions. Packaging applications can be further developed with these composite materials.
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