Pendahuluan: Penyakit Alzheimer adalah penyakit neurodegeneratif yang menyebabkan gangguan progresif pada fungsi perilaku dan kognitif. Penyakit ini merupakan jenis demensia yang paling umum terjadi ...dengan prevalensi yang meningkat setiap tahunnya. Patofisiologi kompleks yang dimiliki penyakit ini menyebabkan belum adanya pengobatan yang efektif untuk penyakit Alzheimer. Tinjauan literatur ini bertujuan untuk meninjau lebih lanjut mengenai potensi Rabies Viral Glycoprotein (RVG)-modified exosomes yang berasal dari Bone Marrow Mesenchymal Stem Cell (BMMSC) melalui aktivasi mikroglial otak yang dapat mereduksi Aβ sebagai terapi kuratif terkini pada penyakit Alzheimer. Metode: Literatur dicari menggunakan situs pencari seperti Google Scholar, Science Direct, ResearchGate, dan NCBI. Kriteria inklusi dan eksklusi digunakan untuk mengeliminasi literatur yang tidak berkaitan sehingga diperoleh 24 literatur. Pembahasan: BMMSC dapat meringankan neuropatologi, penurunan memori, dan defisit perilaku. Selain itu, BMMSC yang ditransplantasikan dapat menghambat kematian sel terkait Aβ dan tau. Sementara itu, terjadi peningkatan regulasi ekspresi sitokin antiinflamasi (IL-10 dan IL-4) dan penurunan regulasi sitokin proinflamasi (TNF-a dan IL-1β). Studi ini menunjukkan bahwa penggunaan BMMSC yang diturunkan dari eksosom yang dimodifikasi RVG lebih baik daripada BMMSC yang diturunkan dari eksosom saja untuk meningkatkan fungsi kognitif pada mencit APP/ PS 1. Kesimpulan: RVG-eksosom derivat BMMSC dapat menghambat kematian sel dengan mengurangi akumulasi Aβ dan tau, menyeimbangkan faktor inflamasi otak, serta meningkatkan fungsi memori dan kognitif. RVG-eksosom BMMSC berpotensi sebagai terapi mutakhir penyakit Alzheimer serta penyakit neurogeneratif lainnya. Saran: Dibutuhkan penelitian lebih lanjut terkait mekanisme molekular, dosis, dan efek samping terapi RVG-eksosom derivate BMMSC pada penyakit Alzheimer.
Kata Kunci: BMMSC, Defisit Memori, Penyakit Alzheimer, Peptida Amiloid β, Sitokin Inflamasi
Introduction: Alzheimer's disease is a neurodegenerative disease that causes progressive impairment of behavioral and cognitive functions. This disease is the most common type of dementia with an increasing prevalence every year. Due to its complex pathophysiology, there is no effective treatment to date for Alzheimer’s disease. This literature review aims to further review the potential of Rabies Viral Glycoprotein (RVG)-modified exosomes from Bone Marrow Mesenchymal Stem Cells (BMMSC) through microglial activation in the brain which can reduce Aβ as the latest curative therapy in Alzheimer's disease. Method: Literature is searched using search engines such as Google Scholar, Science Direct, ResearchGate, and NCBI. Inclusion and exclusion criteria were used to eliminate unrelated journals so that 24 journals were obtained. Discussion: BMMSC can alleviate neuropathology, memory decline, and behavioral deficits. In addition, transplanted BMMSC could inhibit Aβ and tau-associated cell death. Meanwhile, there is an upregulation of anti-inflammatory cytokines (IL-10 and IL-4) and a downregulation of pro-inflammatory cytokines (TNF-a and IL-1β). The study showed that the use of RVG-modified exosomes derived BMMSC was better than exosomes derived BMMSC to improve cognitive function in APP/PS 1 mice. Conclusion: RVG-modified exosomes derived BMMSC can inhibit cell death by reducing Aβ and tau accumulation, balancing brain inflammatory factors, and improving memory and cognitive function. RVG-modified exosomes derived BMMSC has the potential as an advanced therapy for Alzheimer's disease and other neurogenerative diseases. Suggestion: Further research on the molecular mechanism, dosage, and side effects of RVG-modified exosomes derived BMMSC therapy in Alzheimer’s disease is needed.
Keywords: Alzheimer Disease, Amyloid β Peptide, BMMSC, Inflammatory Cytokine, Memory Deficit
Abstract
Objectives
Neuroinflammation is an important factor in the pathogenesis of neurodegenerative disesases. The following study aimed to clarify the effects of β-lactam antibiotics to the ...cholinergic system, on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, considering the structural differences of antibiotics, to evaluate the underlying mechanism of effects provided by protein-antibiotic interactions, and to clarify possible effects of the antibiotics on the aggregation of Aβ-peptides.
Methods
The inhibition/activation mechanisms for each antibiotic were examined kinetically by Ellman method. Destabilization effects of them on amyloid peptide fibrillation were examined and protein-ligand interactions were evaluated with most potent antibiotics by molecular docking studies.
Results
The most powerful inhibitions were detected by the inhibition studies of AChE with ceftazidime (CAZ) and BuChE with amoxicillin (AMX). CAZ was exhibited dose-related dual effect on AChE activity. CAZ was actually the dose-related modifier of AChE. At higher concentrations, CAZ was a nonessential activator of AChE. Molecular docking studies have been confirmed by kinetic studies. Interested β-lactam antibiotics did not prevent fibrillation rate as rifampicin.
Conclusions
Inhibition/activation behaviours of studied β-lactam antibiotics on both cholinesterases may suggest that cholinergic transmission is one of the crucially important components of the β-lactam antibiotics-induced central nervous system adverse reactions.
The objective of this prospective study was to evaluate whether soluble programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) and serum amyloid A1 (SAA1) are potential diagnostic, ...predictive or prognostic biomarkers in lung cancer.
Lung cancer patients (n=115) with advanced metastatic disease, 101 with non-small cell lung cancer, NSCLC (77 EGFR wild-type NSCLC patients on chemotherapy, 15 EGFR mutation positive adenocarcinoma patients, 9 patients with mPD-L1 Expression ≥50% NSCLC - responders to immunotherapy), and 14 patients with small cell lung cancer (SCLC) were examined. ELISA method was used to determine sPD-L1 and SAA1 concentrations in patients' plasma.
Significantly higher blood concentrations of sPD-L1 and SAA1 were noted in lung cancer patients compared with a healthy control group. In PD-L1+ NSCLC patients, a significantly higher sPD-L1 level was noticed compared to any other lung cancer subgroup, as well as the highest average SAA1 value compared to other subgroups.
It seems that sPD-1/PD-L1 might be a potential biomarker, prognostic and/ or predictive, particularly in patients treated with immunotherapy. Serum amyloid A1 has potential to act as a good predictor of patients' survival, as well as a biomarker of a more advanced disease, with possibly good capability to predict the course of disease measured at different time points.
Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterised by periodic inflammatory attacks. We investigated changes in monocyte-granulocyte derived S10012A and chitotriosidase ...in both the attack and silent period of FMF for better estimation of inflammation. Endogenous resolvin was determined for utility to restrict inflammation. This study included 29 FMF patients (15 M/14 F) and 30 healthy controls (15 M/15 F). Serum levels of highly sensitive C-reactive protein, serum amiloid A (SAA), S100A12, chitotriosidase, and resolvin D1 were measured. Age, sex, body mass indexes, and lipids were similar between patients and controls. Biomarkers including hs-CRP, SAA, S100A12, chitotriosidase, and resolvin D1 were higher in the attack period of FMF patients compared to controls (P < 0.001). When FMF patients in the silent period were compared with their attack period, hs-CRP, SAA, and chitotriosidase were found elevated in the attack period (P < 0.001, P < 0.001, and P = 0.02 respectively). Serum levels of SAA, S100A12, chitotriosidase, and resolvin D1 in the silent period of FMF patients were still found elevated compared to healthy controls, indicating subclinical inflammation (P < 0.001, P < 0.001, P = 0.009, and P < 0.001 respectively ). In subgroup analysis, patients with M694V homozygote and heterozygote mutations had higher S10012A and hs-CRP compared to other mutation carriers. Our findings indicate that chitotriosidase and S10012A are useful in diagnosis and detection of subclinical inflammation and/or assessment of disease activity in FMF patients. They could be more informative for inflammation in various disease states compared to hsCRP and SAA. Resolvin D1 is elevated in both the attack and silent periods of FMF. It may be helpful to restrict inflammation.
Odgovor akutne faze upalne reakcije očituje se povećanom sintezom specifičnih proteina poznatih pod nazivom proteini akutne faze. U proteine akutne faze ubrajaju se C-reaktivni protein, serumski ...amiloid A, haptoglobin, alfa-1-glikoprotein, fibrinogen, α 1 kiseli glikoprotein, ceruloplazmin i drugi. Ove proteine najvećim dijelom sintetiziraju hepatociti. U ovom preglednom radu praćene su vrijednosti koncentracija navedenih proteina akutne faze u različitih patoloških stanja pasa i ljudi. Dosadašnja istraživanja ukazuju na značenje ovih proteina pri dijagnosticiranju i praćenju tijeka i ishoda različitih bolesti.
The zebrafish is an excellent animal model to study the formation of the vertebrate vascular network. The small size, the optical translucency, and the ability to model endothelial-specific ...fluorescent transgenic lines in the zebrafish embryo had facilitate, in the past 10 years, the direct visualization of vessels formation and remodeling. Furthermore, zebrafish is an excellent disease model such as for cancer and neurodegenerative diseases. Cerebral amyloid angiopathy (CAA) is a human neurovascular degenerative disease, caused by Amyloid β (Aβ) peptides deposition around brain microvessels, and characterized by vascular brain degenerative changes. By using the zebrafish model, we investigated the effect of Aβ peptides treatment in vessel formation during embryogenesis. We showed that the defects in the vascular remodeling and senescence can be detected, respectively, via staining for alkaline phosphatase activity and β-galactosidase or cyclin-dependent kinase inhibitor p21 expression. We demonstrated that treating zebrafish embryos with these oxidative peptides reduces angiogenesis and promotes premature vascular senescence. In this chapter, we will describe the methods to reveal both angiogenesis and senescence defects upon Aβ peptides treatment of the zebrafish embryos.
Necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal emergency, predominantly affecting low-birth weight, premature infants. Early clinical signs of NEC are nonspecific and ...the laboratory findings are not fully reliable. Its severe morbidities and rapid progression require the application of new biomarkers for early diagnosis and intervention. The complement activation product, C5a (anaphylatoxin) has been reported to be a contributing factor leading to mesenteric ischemia/reperfusion injury which is a predisposing factor in the pathogenesis of NEC. Therefore, our aim was to evaluate the efficacy of serial C5a measurements in the diagnosis and follow-up of NEC. Preterm infants, whose gestational age and weight matched each other, were grouped as controls (n = 23) and NEC (n = 22). Serum levels of C5a, serum amyloid-A (SAA), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured on the third day of life for the control group and on the day of diagnosis (1st day), 3rd and 7th days of the NEC group. C5a, SSA, CRP, and IL-6 levels were significantly higher in the NEC patients compared to the control group (P < 0.05) in the follow-up. Additionally, serum levels of C5a were found to be more accurate than the other parameters for the prediction of death and requirement for surgery at the time of diagnosis (P < 0.05). In conclusion, C5a may be useful as a new marker for both diagnosis and follow-up of infants with NEC in combination with clinical and radiographical findings.
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