3 Biotech, Journal Year: 2024, Volume and Issue: 15(1)
Published: Dec. 11, 2024
Language: Английский
3 Biotech, Journal Year: 2024, Volume and Issue: 15(1)
Published: Dec. 11, 2024
Language: Английский
Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 116, P. 108378 - 108378
Published: Feb. 8, 2025
Language: Английский
Citations
1Talanta, Journal Year: 2025, Volume and Issue: unknown, P. 127790 - 127790
Published: Feb. 1, 2025
Language: Английский
Citations
1Methods and Protocols, Journal Year: 2025, Volume and Issue: 8(3), P. 48 - 48
Published: May 6, 2025
Background: Lafora disease (LD) is an ultra-rare and fatal neurodegenerative disorder with limited therapeutic options. Current treatments primarily address symptoms, modest efficacy in halting progression, thus highlighting the urgent need for novel approaches. Gene therapy, antisense oligonucleotides, recombinant enzymes have recently been, still are, under investigation. Drug repurposing may offer a promising approach to identify new, possibly effective, therapies. Methods: This study aims investigate conditions empagliflozin, SGLT2 (sodium/glucose cotransporter-2) inhibitor, as potential treatment LD establish clinical protocol. Clinical phase: 12-month prospective observational will assess safety of empagliflozin two patients early intermediate stage. The primary endpoints include changes severity epilepsy cognitive function, while secondary motor global autonomy. Multiple instrumental evaluations (including MRI PET 18F-fluorodeoxyglucose) be performed before during treatment. Safety monitoring regular assessments reports adverse events. Preclinical In silico studies (using both molecular docking calculations reverse ligand-based screening) vitro cell-based assays allow us effects (and other gliflozins) on some key targets likely implicated pathogenesis, such GLUT1, GLUT3, glycogen synthase (hGYS), phosphorylase (GP), suggested literature digital platforms target fishing. Results: expected outcome this twofold, i.e., (i) assessing tolerability (ii) gathering preliminary data its improving neurologic features. Additionally, provide new insights into mechanisms through which exert LD. Conclusion: findings are evidence support
Language: Английский
Citations
0Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14
Published: Jan. 23, 2024
The goal of this work is to use a variety in-silico techniques identify anti-diabetic agents against DPP-IV enzyme from five main curcumin analogues. To produce the successful molecules, analogues were docked into active site enzyme. In comparison control molecule (Saxagliptin, −6.9 kcal/mol), all compounds have highest binding affinity (-7.6 −7.7 kcal/mol) for These underwent further testing studies on drug-likeness, pharmacokinetics, and acute toxicity see efficacy safety compounds. assess stability docking complex posture identified during experiment, our study got THC as lead compound, which was then exposed 200 ns molecular dynamic simulation PCA analysis. Additionally, DFT calculations conducted determine thermodynamic, orbital, electrostatic potential characteristics compound. Overall, chemical has shown strong drug-like properties, non-toxic, sizable
Language: Английский
Citations
3International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 262, P. 130090 - 130090
Published: Feb. 9, 2024
Language: Английский
Citations
3Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(11), P. 1620 - 1620
Published: Nov. 16, 2023
The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. lack safe effective causal therapy in cognitive decline an aggravating factor requires investigations into the repurposing commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are new efficient class hypoglycemic drugs and, due their pleiotropic effects, have indications that go beyond diabetes. There emerging data from murine studies SGLT2i can cross blood–brain barrier may neuroprotective increasing brain-derived neurotrophic (BDNF), reducing amyloid burden, inhibiting acetylcholinesterase (AChE) restoring circadian rhythm mammalian target rapamycin (mTOR) activation. current study investigates effect donepezil, under separate or combined 21-day treatment on AD-relevant behaviors brain pathology mice. canagliflozin was found significantly improve novelty preference index percentage time spent open arms maze novel object recognition elevated plus test, respectively. In addition, decreased AChE activity, mTOR glial fibrillary acidic protein expression. results also recorded acetylcholine M1 receptor canagliflozin-treated mice compared scopolamine group. hippocampus, reduced microgliosis astrogliosis males, but not female These findings emphasize value clinical practice. By represents compound resembles AD-registered therapies this respect, supporting need for further evaluation dementia trials.
Language: Английский
Citations
8Aging, Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 1, 2024
Vascular calcification (VC) is directly related to high mortality in chronic kidney disease (CKD), and cellular apoptosis of vascular smooth muscle cells (VSMCs) a crucial process the initiation VC. Microtubule affinity-regulating kinase 4 (Mark4), known as serine/threonine protein kinase, can induce cell autophagy by modulating Akt phosphorylation. However, potential functions molecular mechanisms Mark4 VSMCs need be further explored. Initially, our data indicated that mRNA expression was prominently elevated phosphorus-stimulated human compared with other members Marks. Consistently, found significantly increased calcified arteries both CKD patients rats. In vitro, silencing suppressed apoptosis-specific marker promoting phosphorylation, finally attenuating induced phosphate. Mechanically, transcription factor Sp1 enriched promoter region modulated transcription. Moreover, SET domain-containing 8 (Setd8) proved interact jointly participated transcriptional regulation Mark4. Finally, rescue experiments revealed Setd8 contributed expression. conclusion, these findings reveal transcriptionally activated Sp1, which interacted Setd8, promote through Akt-mediated antiapoptotic effects, suggesting represents potent promising therapeutic target for VC CKD.
Language: Английский
Citations
2CNS & Neurological Disorders - Drug Targets, Journal Year: 2023, Volume and Issue: 23(8), P. 931 - 940
Published: Oct. 19, 2023
Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological function. The ability to detect and treat these conditions successfully is crucial for ensuring the best possible quality life people who suffer from them. development effective new methods managing treating neurodegenerative illnesses has been made recent developments in computer technology. In this overview, we take look at prospects applying computational approaches, such as drug design, AI, ML, DL, treatment diseases. To review current state field, article discusses potential early disease detection, quantifying progression, understanding underlying biological mechanisms diseases, well challenges associated with approaches future directions. Moreover, it delves into creation models individualization care concludes suggestions studies clinical applications, highlighting advantages disadvantages using techniques
Language: Английский
Citations
5Aging, Journal Year: 2024, Volume and Issue: 16(16), P. 11994 - 12007
Published: Aug. 22, 2024
Background: How a person's Parkinson disease (PD) risk is affected by dipeptidyl peptidase-4 (DPP-4) inhibitors remains unclear. We evaluated the association of PD with use these in individuals diagnosed as having diabetes mellitus (DM). Methods: Individuals new-onset DM were enrolled into case group and comparison group, comprising patients who received DPP-4 inhibitor sulfonylurea, respectively. These groups matched through propensity score matching on basis income level, gender, urbanization enrollment year, age, complications severity index score. The was divided subgroups whether they had cumulative defined daily dose (cDDD) <75, 75–150, or >150. inhibitor–PD Cox proportional hazards model. Bonferroni adjustment test employed to adjust P-values reduce false positive rate. Results: Compared those (treatment sulfonylurea), cDDD >150 hazard ratio (HR) 1.30 for development (95% confidence interval [CI]: 0.97-1.73; adjusted P = .263); HRs <75 75–150 0.95 CI: 0.71-1.27; .886) 1.06 0.75-1.50; .886), noted nonsignificant differences regarding associations between various (linagliptin, saxagliptin, sitagliptin, vildagliptin) after any individual (adjusted > .05). Conclusions: discovered this study not be associated increased risk. This result confirmed when analysis conducted individually 4 investigated (sitagliptin, linagliptin, vildagliptin).
Language: Английский
Citations
1Aspects of Molecular Medicine, Journal Year: 2024, Volume and Issue: 4, P. 100053 - 100053
Published: Sept. 5, 2024
Language: Английский
Citations
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