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Anticonvulsant potential of rosuvastatin in combination with carbamazepine and valproate in animal models of epilepsy

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World Journal of Methodology 2025年第2期15卷 137-144页

作者： Vandana Tayal Akash Mandal Ijasul Haque M akhilesh Mishra Bhupinder s kalra Vandana Roy Department of Pharmacology Maulana Azad Medical CollegeNew Delhi 110002India Department of Pharmacology MES Medical CollegePerintalmanna 679338KeralaIndia Department of Central Animal Facility Maulana Azad Medical CollegeNew Delhi 110002India

BACkGROUND Epilepsy impacts millions of people,with many not responding to existing *** evidence links neuroinflammatory processes to *** exhibit anti-inflammatory and neuroprotective properties,potentially offering antiepileptic *** To evaluate the anticonvulsant effects of rosuvastatin in animal models of *** Ninety-six albino mice were divided into 16 *** the maximal electroshock seizure(MEs)model,eight groups received intraperitoneal vehicle,carbama-zepine,rosuvastatin,or a *** measured included seizure protection[tonic hind limb extension(THLE)],duration of THLE,seizure duration,and *** the pentylenetetrazol(PTZ)model,eight groups were pretreated with vehicle,valproate,rosuvastatin,or a combination,with outcomes measured as seizure latency,seizure duration,and *** In the MEs model,rosuvastatin exhibited protection against THLE in a small percentage of *** shortens the duration of THLE in a dose-dependent ***,none of these were statistically significant com-pared to the control *** combination of rosuvastatin 10 mg/kg with carbamazepine 4 mg/kg resulted in a significant reduction in seizure duration compared to the control group,better than carbamazepine alone at 4 mg/kg and 6 mg/*** the PTZ model,rosuvastatin alone showed no significant effects on latency,duration of seizure,or ***,rosuvastatin 10 mg/kg combined with valproate 100 mg/kg significantly delayed the onset of seizures,seizure duration and mortality percentage,better than valproate alone at 100 mg/*** Rosuvastatin enhanced the anticonvulsant effects of carbamazepine and *** studies are required to explore the antiepileptic potential of rosuvastatin at various doses,durations,dosage forms,routes and models.

关键词： Antiepileptic Anticonvulsant statins Rosuvastatin Maximal electroshock seizure Pentylenetetrazol

Perianal Crohn’s disease:still more questions than answers

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World Journal of Gastroenterology 2024年第39期30卷 4260-4266页

作者： akhilesh swaminathan Miles P sparrow Department of Medicine University of OtagoChristchurch 8011CanterburyNew Zealand Department of Gastroenterology Alfred HealthMelbourne 3004VictoriaAustralia Department of Gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of Gastroenterology Alfred Health and School of Translational MedicineMonash UniversityMelbourne 3004VictoriaAustralia

In this editorial we comment on the article by Pacheco et al published in a recent issue of the World Journal of *** focus specifically on the burden of illness associated with perianal fistulizing Crohn’s disease(PFCD)and the diagnostic and therapeutic challenges in the management of this ***-ving evidence has shifted the diagnostic framework for PFCD from anatomical classification systems,to one that is more nuanced and patient-focused to drive ongoing decision *** editorial aims to reflect on these aspects to help clinicians face the challenge of PFCD in day-to-day clinical practice.

关键词： Perianal Crohn’s disease Crohn’s disease classification Disease severity Crohn’s disease treatment Anorectal malignancy

Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： krisztián Pajer Tamás Bellák Antal Nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(khyeam et al.,2021).

关键词： injured capacity modified

Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Unveiling the impact:COVID-19's influence on bacterial resistance in the kingdom of Bahrain

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World Journal of Virology 2025年第1期14卷 83-98页

作者： Nermin k saeed safiya k Almusawi Noor A Albalooshi Mohammed Al-Beltagi Medical Microbiology section Department of PathologySalmaniya Medical ComplexGovernmental HospitalsManama 12Bahrain Medical Microbiology section Department of PathologyRoyal College of Surgeons in Ireland-Medical University of BahrainBusaiteen 15503MuharraqBahrain Department of Paediatrics Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671AlgharbiaBahrain

BACkGROUND Antibiotic resistance is a growing global health threat,and understanding local trends in bacterial isolates and their susceptibility patterns is crucial for effective infection control and antimicrobial *** coronavirus disease 2019(COVID-19)pandemic has introduced additional complexities,potentially influencing these *** To analyze trends in bacterial isolates and their antibiotic susceptibility patterns at salmaniya Medical Complex from 2018 to 2023,with a specific focus on the impact of the COVID-19 pandemic on these *** A retrospective analysis of microbiological data was conducted,covering the period from 2018 to *** study included key bacterial pathogens such as Escherichia coli(***),klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,and staphylococcus aureus,among *** antibiotic susceptibility profiles of these isolates were assessed using standard laboratory *** contextualize the findings,the findings were compared with similar studies from other regions,including China,India,Romania,saudi Arabia,the United Arab Emirates,Malaysia,and United *** The study revealed fluctuating trends in the prevalence of bacterial isolates,with notable changes during the COVID-19 *** example,a significant increase in the prevalence of staphylococcus aureus was observed during the pandemic years,while the prevalence of *** showed a more variable *** resistance rates varied among the different pathogens,with a concerning rise in resistance to commonly used antibiotics,particularly among klebsiella pneumoniae and ***,the study identified an alarming increase in the prevalence of multidrug-resistant(MDR)strains,especially within klebsiella pneumoniae and *** *** impact of the COVID-19 pandemic on these trends was evident,with shifts in the frequency,resistance patterns,and the emergence of MDR bacteria among several key ***

关键词： Multidrug-resistant organisms Antibiotic susceptibility COVID-19 pandemic Antimicrobial stewardship Bacterial isolates salmaniya Medical Complex Bahrain

A Pair of Pseudo-differential Operators Involving Index Whittaker Transform in L_(2)^(a) (R_(+);m_(a)(x)dx)

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Acta Mathematica sinica,English series 2024年第6期40卷 1420-1430页

作者： Jeetendrasingh MAAN akhilesh PRAsAD Department of Mathematics and Computing Indian Institute of Technology(Indian School of Mines)Dhanbad-826004India

Pseudo-differential operators(PDO)Q(x,L_(a,x))and Q(x,L_(a,x))involving the index Whittaker transform are *** for these operators in Hilbert space L_(2)^(a)(R+;m_(a)(x)dx)are obtained.A symbol classΩis *** product an... 详细信息

关键词： Pseudo-differential operator index Whittaker transform confluent hypergeometric functions Hilbert space

synthetic and biological studies on a cyclopolypeptide of plant origin

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2008年第5期9卷 391-400页

作者： Rajiv DAHIYA akhilesh kUMAR Department of Pharmaceutical Chemistry Rajiv Academy for Pharmacy

Objective:A natural cyclic peptide previously isolated from Citrus medica was synthesized by coupling of tetrapep-tide units Boc-Leu-Pro-Trp-Leu-OMe and Boc-Ile-Ala-Ala-Gly-OMe after proper deprotection at carboxyl and amino terminals followed by cyclization of linear octapeptide segment. Methods:solution phase technique was adopted for the synthesis of cyclooctapeptide-sarcodactylamide. Required tetrapeptide units were prepared by coupling of Boc-protected dipeptides viz. Boc-Leu-Pro-OH and Boc-Ile-Ala-OH with respective dipeptide methyl esters Trp-Leu-OMe and Ala-Gly-OMe. Cyclization of linear octapeptide unit was done by p-nitrophenyl ester method. The structure of synthesized cyclopolypeptide was elucidated by FTIR,1H NMR,13C NMR,FABMs spectral data and elemental analysis. The newly synthesized peptide was evaluated for dif-ferent pharmacological activities including antimicrobial,anthelmintic and cytotoxic activities. Results:synthesis of sarcodac-tylamide was accomplished with >78% yield utilizing dicyclohexylcarbodiimide(DCC) as coupling agent. Newly synthesized peptide possessed potent cytotoxic activity against Dalton's lymphoma ascites(DLA) and Ehrlich's ascites carcinoma(EAC) cell lines,in addition to moderate anthelmintic activity against earthworms Megascoplex konkanensis,Pontoscotex corethruses and Eudrilus sp. Moreover,cyclopolypeptide displayed good antimicrobial activity against pathogenic fungi Candida albicans and Gram-negative bacteria Pseudomonas aeruginosa,in comparison to standard drugs griseofulvin and ciprofloxacin. Conclusion:solution phase technique employing DCC and triethylamine(TEA) as base proved to be effective for the synthesis of natural cyclooctapeptide. N-methyl morpholine(NMM) was found to be a better base for the cyclization of linear octapeptide unit in comparison to TEA and pyridine.

关键词： Cyclic octapeptide Citrus medica var. sarcodactylis sarcodactylamide Peptide synthesis Anthelmintic activity Antimicrobial activity Cytotoxicity