Alzheimer's disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer's sufferers continue to ...deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer's disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity.
In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex's dynamic development.
As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.
Background
The present study pointed to evaluate the role of
Triticum aestivum
ethanolic extract (TAEE) in prophylactic and curative regimens on sodium oxalate (NaOx)-prompted lithiasis. Forty-eight ...rats were divided into the following regimen’s group (24 rats/regimen). Groups I, II, III, and IV served as prophylactic groups and divided as: group I is a vehicle control received 5% DMSO (vehicle). All the remaining groups received NaOx (70 mg/kg b.wt; i.p.). Group II is NaOx lithiatic group, groups III and IV received TAEE and cystone prophylactically at doses of 500 and 750 mg/kg b.wt, respectively, since 1st day to 7th day of lithiasis stimulation. Groups V, VI, VII, and VIII served as curative groups that divided as the prophylactic ones but TAEE and cystone administered from 7th day to 14th day of lithiasis stimulation.
Results
Lithiatic rats co-/post-treated with TAEE and cystone raised the urinary volume significantly. Also, TAEE showed modulatory effect in inhibiting and curative stone creation. Significant decreases were observed in the calcium and phosphate contents in urine or serum beside the increased magnesium value in lithiatic rats co-/post-treated with TAEE. TAEE significantly ameliorates the kidney function markers, which proposes its antilithiatic role. Moreover, lithiatic rats co-/post-treated with TAEE significantly diminished oxidative injury evoked by NaOx.
Conclusions
TAEE has antilithiatic role that may be returned to its diuretic and antioxidant activity in addition to its bioactive components including ferulic acid and phytic acid that have the inhibitory properties on crystallization calcium oxalate by lowering the content of stone promotor constituents.
The current study regarding the effects of larval diets on the life table parameters of dengue mosquitoes, Aedes aegypti was conducted under laboratory conditions at 27 ± 2 °C and 60 ± 5% relative ...humidity at NIFA (Nuclear Institute for Food and Agriculture) Peshawar, Pakistan. The data on life table parameters of Ae. aegypti reared on Diet 1 (replacement diet), Diet 2 (Khan's diet for Anopheles), Diet 3 (Khan's modified diet) and Diet 4 (IAEA diet) were analyzed using the age-stage, two-sex life table software. Diet 4 (IAEA) was used as a control for comparison. The results indicated that significantly maximum percentage of egg hatching of Ae. aegypti was observed when reared on Diet 4 (73.86%) and Diet 3 (72.90%), while less % of egg hatching was recorded in Diet 1 (40.67%) and Diet 2 (55.53%). The data further showed that the Diet 3 had a highest intrinsic rate of increase (r) (0.097 ± 5.68 day
), finite rate of increase (λ) (1.10 ± 6.26 day
) and net reproductive rate (R
) (11.99 ± 1.52 eggs/female) followed by Diet 2 and Diet 4. The mean generation time (T) of Ae. aegypti reared on Diet 3 (23.67 ± 0.86 days) and Diet 1 (24.05 ± 0.61 days) was significantly shorter than Diet 2 (26.15 ± 0.71 days) and Diet 4 (26.41 ± 0.38 days). The overall results revealed that Diet 3 showed good results at different life table parameters of Ae. aegypti and can be used as the preferred diet in the Sterile Insect Technique (SIT) where the mass culture of mosquitoes is required.
The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with ...minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy,
H nuclear magnetic resonance (NMR) spectroscopy, and
C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.
Mesoporous carbon is a promising material having multiple applications. It can act as a catalytic support and can be used in energy storage devices. Moreover, mesoporous carbon controls body's oral ...drug delivery system and adsorb poisonous metal from water and various other molecules from an aqueous solution. The accuracy and improved activity of the carbon materials depend on some parameters. The recent breakthrough in the synthesis of mesoporous carbon, with high surface area, large pore-volume, and good thermostability, improves its activity manifold in performing functions. Considering the promising application of mesoporous carbon, it should be broadly illustrated in the literature. This review summarizes the potential application of mesoporous carbon in many scientific disciplines. Moreover, the outlook for further improvement of mesoporous carbon has been demonstrated in detail. Hopefully, it would act as a reference guidebook for researchers about the putative application of mesoporous carbon in multidimensional fields.
Gastric ulcer is a disturbing disease that impacts many people worldwide. Pioglitazone (Piog), a thiazolidinedione, and ligustrazine (Ligu), a natural component of
Ligusticum chuanxiong
possess ...gastroprotective properties. However, the underlying mechanism is not well elucidated. The present study aimed to investigate the gastroprotective effects of Piog (15 mg/kg, p.o.), Ligu (15 mg/kg, p.o.), and their combination against ethanol-induced gastric ulcer in rats. Omeprazole (10 mg/kg) was used as a standard. Pre-treatment for 7 days with Piog, Ligu, and (Piog+Ligu) effectively alleviated ethanol-predisposed oxidative stress and inflammation through restoring HO-1, GSH, and SOD tissue levels and decreasing elevated MDA, TNF-α, ICAM, I-NOS, and IL-1β contents. Moreover, Piog, Ligu, and (Piog+Ligu) markedly inhibited the ethanol-induced increase of gastric NF-KB and BAX. In contrast, this pre-treatment regimen significantly accelerated protein expression of SIRT1, Nrf2, and Bcl-2, along with autophagic proteins, ATG5 and Beclin. Interestingly, macroscopic, histopathological examination and mucin content were in harmony with previous results, where pre-treatment with Piog, Ligu, and (Piog+Ligu) showed a declined mucosal injury as evidenced by the remarkable decrease of the ulcer area percentage by 62.3%, 38.7%, and 91.2%, respectively, compared to the ethanol-ulcerated group. In conclusion, Piog and Ligu exhibited remarkable gastroprotective properties. Our study was the first to show that Piog, Ligu, and (Piog+Ligu) ameliorated oxidative stress, inflammation, and apoptosis and accelerated the autophagic process via the upregulation of the upstream SIRT1 protein. It is worth mentioning that future studies are needed to pave the way for the clinical use of Piog and Ligu as gastro-protective agents.
Microcystin- (MC-) LR is the most frequent cyanotoxin produced by Microcystis aeruginosa cyanobacteria in the contaminated freshwater environment. MC represents a health hazard to humans and animals. ...Therefore, the present study was designed to evaluate the potential ameliorative effect of thymoquinone (TQ) and/or piperine (PP) against MC toxicity in mice. Fifty-six mice were randomly divided into seven experimental groups. Group I is the normal control that received distilled water for 21 days; Group II (TQ) was treated with TQ (10 mg/kg, i.p) for 21 days; Group III (PP) was treated with PP (25 mg/kg, i.p) for 21 days; Group IV (MC) was treated with MC (10 μg/kg, i.p) for 14 days and served as the toxic control; and Groups V, VI, and VII received TQ and/or PP 7 days prior to MC and continued for 14 days with MC. The results revealed that MC elicited hepatotoxicity and neurotoxicity which was evident due to the significant elevation of serum AST, ALT, γGT, ALP, LDH, IL-1β, IL-6, and TNF-α levels. Furthermore, MC markedly increased MDA and NO contents along with reduction of GSH, SOD, CAT, and GSH-Px in liver and brain tissues. The electron transport chain may be a possible target for MC. TQ and/or PP ameliorated the MC-mediated oxidative damage in the liver and brain which might be attributed to their antioxidant properties. However, the concurrent treatment of TQ and PP showed the best regimen as a result of the PP-enhanced bioavailability of TQ.
Cancer treatment is improving widely over time, but finding a proper defender to beat them seems like a distant dream. The quest for identification and discovery of drugs with an effective action is ...still a vital work. The role of a membrane protein called P-glycoprotein, which functions as garbage chute that efflux the waste, xenobiotics, and toxins out of the cancer cells acts as a major reason behind the therapeutic failure of most chemotherapeutic drugs. In this review, we mainly focused on a multiple strategies by employing 5-Fluorouracil, curcumin, and lipids in Nano formulation for the possible treatment of colorectal cancer and its metastasis. Eventually, multidrug resistance and angiogenesis can be altered and it would be helpful in colorectal cancer targeting.We have depicted the possible way for the depletion of colorectal cancer cells without disturbing the normal cells. The concept of focusing on multiple pathways for marking the colorectal cancer cells could help in activating one among the pathways if the other one fails. The activity of the 5-Fluorouracil can be enhanced with the help of curcumin which acts as a chemosensitizer, chemotherapeutic agent, and even for altering the resistance. As we eat to survive, so do the cancer cells. The cancer cells utilize the energy source to stay alive and survive. Fatty acids can be used as the energy source and this concept can be employed for targeting the colorectal cancer cells and also for altering the resistant part.
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•Colorectal cancer treatment failure is multidrug resistance and reoccurrence.•Resistance exhibits with the action of P-glycoprotein, which results in metastasis.•Lipids, 5-Fluorouracil and curcumin combination relapse colorectal cancer.•This dual drug approach provides a synergistic activity.•Focusing on metastasis with lymph node targeting with lipids.
Nanoparticles play a vital role in cancer treatment to deliver or direct the drug to the malignant cell, avoiding the attacking of normal cells. The aim of the study is to formulate ...folic-acid-modified chitosan nanoparticles for colon cancer. Chitosan was successfully conjugated with folic acid to produce a folic acid-chitosan conjugate. The folate-modified chitosan was loaded with 5-FU using the ionic gelation method. The prepared nanoparticles were characterized for size, zeta potential, surface morphology, drug contents, entrapment efficiency, loading efficiency, and in vitro release study. The cytotoxicity study of the formulated nanoparticles was also investigated. The conjugation of folic acid with chitosan was confirmed by FTIR and NMR spectroscopy. The obtained nanoparticles were monodispersed nanoparticles with a suitable average size and a positive surface charge. The size and zeta potential and PDI of the CS-5FU-NPs were 208 ± 15, 26 ± 2, and +20 ± 2, respectively, and those of the FA-CS-5FU-NPs were 235 ± 12 and +20 ± 2, respectively, which are in the acceptable ranges. The drug contents' % yield and the %EE of folate-decorated NPs were 53 ± 1.8% and 59 ± 2%, respectively. The in vitro release of the FA-CS-5FU-NPs and CS-5FU-NPs was in the range of 10.08 ± 0.45 to 96.57 ± 0.09% and 6 ± 0.31 to 91.44 ± 0.21, respectively. The cytotoxicity of the nanoparticles was enhanced in the presence of folic acid. The presence of folic acid in nanoparticles shows much higher cytotoxicity as compared to simple chitosan nanoparticles. The folate-modified nanoparticles provide a potential way to enhance the targeting of tumor cells.
In this focused progress review, the most widely accepted methods of transdermal drug delivery are hypodermic needles, transdermal patches and topical creams. However, microneedles (MNs) (or ...microneedle arrays) are low-invasive 3D biomedical constructs that bypass the skin barrier and produce systemic and localized pharmacological effects. In the past, biomaterials such as carbohydrates, due to their physicochemical properties, have been extensively used to manufacture microneedles (MNs). Due to their wide range of functional groups, carbohydrates enable the design and development of tunable properties and functionalities. In recent years, numerous microneedle products have emerged on the market, although much research needs to be undertaken to overcome the various challenges before the successful introduction of microneedles into the market. As a result, carbohydrate-based microarrays have a high potential to achieve a future step in sensing, drug delivery, and biologics restitution. In this review, a comprehensive overview of carbohydrates such as hyaluronic acid, chitin, chitosan, chondroitin sulfate, cellulose and starch is discussed systematically. It also discusses the various drug delivery strategies and mechanical properties of biomaterial-based MNs, the progress made so far in the clinical translation of carbohydrate-based MNs, and the promotional opportunities for their commercialization. In conclusion, the article summarizes the future perspectives of carbohydrate-based MNs, which are considered as the new class of topical drug delivery systems.
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