BACKGROUND: Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism.
METHOD: Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers.
RESULTS: Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations.
CONCLUSION: We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.
OBJECTIVES: The objectives of this study are to examine the influence of newly identified mutations on the interaction between c-Src and the HK2 enzyme and to discover potent phytocompounds capable of disrupting this interaction.
METHODS: In this study, we utilized molecular docking to check the effect of the identified mutation on the binding of c-Src with HK2. Virtual drug screening, MD simulation, and binding free energy were employed to identify potent drugs against the binding interface of c-Src and HK2.
RESULTS: Among these mutations, six (W151C, L272P, A296S, A330D, R391H, and P434A) were observed to significantly disrupt the stability of the c-Src structure. Additionally, through molecular docking analysis, we demonstrated that the mutant forms of c-Src exhibited high binding affinities with HK2. The wildtype showed a docking score of -271.80 kcal/mol, while the mutants displayed scores of -280.77 kcal/mol, -369.01 kcal/mol, -324.41 kcal/mol, -362.18 kcal/mol, 266.77 kcal/mol, and -243.28 kcal/mol for W151C, L272P, A296S, A330D, R391H, and P434A respectively. Furthermore, we identified five lead phytocompounds showing strong potential to impede the binding of c-Src with HK2 enzyme, essential for colon cancer progression. These compounds exhibit robust bonding with c-Src with docking scores of -7.37 kcal/mol, -7.26 kcal/mol, -6.88 kcal/mol, -6.81 kcal/mol, and -6.73 kcal/mol. Moreover, these compounds demonstrate dynamic stability, structural compactness, and the lowest residual fluctuation during MD simulation. The binding free energies for the top five hits (-42.44±0.28 kcal/mol, -28.31±0.25 kcal/mol, -34.95±0.44 kcal/mol, -38.92±0.25 kcal/mol, and -30.34±0.27 kcal/mol), further affirm the strong interaction of these drugs with c-Src which might impede the cascade of events that drive the progression of colon cancer.
CONCLUSION: Our findings serve as a promising foundation, paving the way for future discoveries in the fight against colorectal cancer.
METHOD: C-reactive Protein (CRP) is a commonly used inflammatory marker in orthopedic surgery and has proven to be a valuable biomarker for diagnosing and monitoring infections. Specifically, CRP aids in the early identification of postoperative infections. This research work has focused on developing a highly sensitive CRP biosensor using iron oxide nanomaterial-modified dielectric sensors.
RESULT: Gold Urchin (GU)-conjugated aptamers and antibodies were used as probes and attached to the electrode via amine linkers. The aptamer-GU-antibody-modified electrode detected CRP at concentrations as low as 1 pg/mL, with an R2 value of 0.9942. Furthermore, CRP-spiked serum exhibited an increase in current response at all concentrations of CRP, indicating selective detection of CRP. Additionally, control experiments using complementary sequences of the aptamer, relevant proteins, and non-immune antibodies did not enhance the current responses, confirming the specific identification of CRP.
CONCLUSION: The sensing strategy has enabled the detection of CRP at its lowest levels, facilitating the identification of infections during orthopedic surgery and subsequent treatment.
OBJECTIVE: In this research, we investigated how miR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 affect apoptosis in hypoxic mice.
METHODS: On the first and third days after delivery, the YKL40, HIF-1a, HVCN1, and S100b genes were compared between two groups of preterm infants with and without maternal inflammation. Afterward, the miRNAs were transfected into cell lines to monitor variations in YKL40, HIF-1a, HVCN1, and S100b gene expression and nerve cell apoptosis. We changed the expression of S100b, HVCN1, and HIF-1a genes by using specific siRNAs injected into mice. Using real-time PCR, Western blotting, flow cytometry (FCM), and immunofluorescence, and changes in gene expression were evaluated (IHC).
RESULTS: HVCN1 gene expression showed a strong negative correlation with epilepsy in both groups of infants (P<0.001). Significant correlations between epilepsy and the expression levels of the S100b, YKL40, and HIF-1a genes were found (P<0.001). According to FCM, after transfecting miRNA-431 and miRNA-34a into cell lines, the apoptosis index (A.I.) were 41.6 3.3 and 34.5 5.2%, respectively, while the A.I. were 9.6 2.7 and 7.1 4.2% after transfecting miRNA-21 and miRNA-138. MiR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 were simultaneously injected into hypoxic mice, and IHC double-labeling revealed that this reduced apoptosis and seizures compared to the hypoxic group.
CONCLUSION: Our findings demonstrate that miR-138-siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 injections prevent cerebral ischemia-induced brain damage in hypoxia mice by increasing HVCN1 and HIF-1a and decreasing S100b, which in turn lessens apoptosis and epilepsy in hypoxic mice.