Epigenetics: A novel therapeutic approach for the treatment of Alzheimer\u27s disease

Alzheimer\u27s disease (AD) is the most common type of dementia in the elderly. It is characterized by the deposition of two forms of aggregates within the brain, the amyloid β plaques and tau neurofibrillary tangles. Currently, no disease-modifying agent is approved for the treatment of AD. Approved pharmacotherapies target the peripheral symptoms but they do not prevent or slow down the progression of the disease. Although several disease-modifying immunotherapeutic agents are in clinical development, many have failed due to the lack of efficacy or serious adverse events. Epigenetic changes including DNA methylation and histone modifications are involved in learning and memory and have been recently highlighted for holding promise as potential targets for AD therapeutics. Dynamic and latent epigenetic alterations are incorporated in AD pathological pathways and present valuable reversible targets for AD and other neurological disorders. The approval of epigenetic drugs for cancer treatment has opened the door for the development of epigenetic drugs for other disorders including neurodegenerative diseases. In particular, methyl donors and histone deacetylase inhibitors are being investigated for possible therapeutic effects to rescue memory and cognitive decline found in such disorders. This review explores the area of epigenetics for potential AD interventions and presents the most recent findings in this field

Communication Skills and their Relationship to Quality of Life and Aggressive Behavior Among a Sample of Adolescent Female Students in Zarqa Governorate

The study aimed to find out the level of each of the communication skills, the quality of life, and the aggressive behavior of a sample of adolescent female students in Zarqa Governorate. The study sample consisted of (1127) female students. To achieve the objectives of the study, the two researchers developed a measure of communication skills, quality of life, and aggressive behavior. The results of the study showed a medium level of communication skills, quality of life, and aggressive behavior. Moreover, the results showed that there are statistically significant differences in the level of each of the communication skills due to the variable of adolescence in favor of the late stage; and in the quality of life in favor of the early stage; and in aggressive behavior in favor of the middle stage. The results indicated a positive correlation between communication skills and quality of life, and a negative relationship between communication skills and aggressive behavior. With regard to the variables that predicted the female students\u27 communication skills, it was found that the predictive variables are: quality of life, followed by aggressive behavior. The study recommends developing the communication skills of female students in general and adolescent girls in particular, in addition to holding counseling courses for adolescent girls that work to develop the quality of life, and conducting treatment counseling programs for students who suffer from a high level of aggressive behavior

Short-term treatment with tolfenamic acid improves cognitive functions in Alzheimer\u27s disease mice

Tolfenamic acid lowers the levels of the amyloid precursor protein (APP) and amyloid beta (Aβ) when administered to C57BL/6 mice by lowering their transcriptional regulator specificity protein 1 (SP1). To determine whether changes upstream in the amyloidogenic pathway that forms Aβ plaques would improve cognitive outcomes, we administered tolfenamic acid for 34 days to hemizygous R1.40 transgenic mice. After the characterization of cognitive deficits in these mice, assessment of spatial learning and memory functions revealed that treatment with tolfenamic acid attenuated long-term memory and working memory deficits, determined using Morris water maze and the Y-maze. These improvements occurred within a shorter period of exposure than that seen with clinically approved drugs. Cognitive enhancement was accompanied by reduction in the levels of the SP1 protein (but not messenger RNA [mRNA]), followed by lowering both the mRNA and the protein levels of APP and subsequent Aβ levels. These findings provide evidence that tolfenamic acid can disrupt the pathologic processes associated with Alzheimer\u27s disease (AD) and are relevant to its scheduled biomarker study in AD patients

Clinical outcomes of COVID-19 in hemodialysis patients

BackgroundThe coronavirus disease 2019 (COVID-19) is known for its effects on the respiratory system. Three years after the pandemic morbid and mortal consequences, growing evidence is showing that the disease also has adverse outcomes and complications on additional organs including the kidneys. This study aims at investigating the effects of COVID-19 on hemodialysis patients receiving services at Palestine Medical Complex (PMC) kidney dialysis department, and to identify mortality related risk factors.MethodsIn April 2022, data was collected using the electronic medical records system for the dialysis department at PMC. The study included all PMC hemodialysis patients that were infected with COVID-19 between January 2020–April 2022. The collected data included patient demographics, clinical features, laboratory tests, dialysis frequency and the disease outcome.ResultsThe results showed that the patients’ outcomes and dialysis frequency were impacted by their blood urea nitrogen (BUN), serum creatinine (SCr) and calcium levels. About one third of the study population died after being infected with COVID-19. The frequency of dialysis was also affected by the presence of comorbidities like hypertension, diabetes mellitus (DM) and myocardial infarction (MI).ConclusionThis study found that there was a high mortality rate within the hemodialysis patients infected with COVID-19. Having comorbidities affected the frequency of dialysis following COVID-19 infection. Dialysis patients should be protected from infections such as COVID-19 and their comorbidities should be monitored and kept under control as much as possible

Lifespan profiles of Alzheimer's disease–associated genes and their products in monkeys and mice.

Alzheimer's disease (AD) is characterized by plaques of amyloid–beta (Aβ) peptide, cleaved from amyloid–β precursor protein (AβPP). Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice, and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AβPP mRNA, AβPP protein, and Aβ levels in rodents and primates. We also tracked a transcriptional regulator of the AβPP gene, specificity protein 1 (SP1), and the β amyloid precursor cleaving enzyme (BACE1). In mice, AβPP and Sp1 mRNA and their protein products were elevated late in life; Aβ levels declined in old age. In monkeys, Sp1, AβPP, and BACE1 mRNA declined in old age, while protein products and Aβ levels rose. Proteolytic processing in both species did not match production of Aβ. In primates, AβPP and Sp1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products, as well as Aβ levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age–related diseases

Composition, Anticholinesterase and Antipedicular Activities of Satureja capitata L. Volatile Oil

The emergence of resistance for antipedicular agents and the need of potent acetylcholinesterase (AChE) therapeutics for the treatment of a neurodegenerative disorder such as Alzheimer disease has led researchers to the exploration of new therapeutic alternatives such as natural volatile oils. Therefore, the current investigation aimed to identify the components of Satureja capitata L. volatile oil (VO), and examine the VO anticholinesterase, and antipedicular activities. The plant phytoconstituents were identified using Gas chromatography mass spectrometry (GC-MS) method, while the anticholinesterase activity was determined against butyryl- and acetyl-cholinesterase using Ellman’s method. In addition, antipedicular activity was established using the diffusion method. The obtained GC-MS results identified 16 compounds in S. capitata VO with the major constituents being carvacrol, γ-terpinene, and p-cymene. Anticholinesterase analysis showed a marked inhibition potential against acetyl- and butyryl-cholinesterase enzymes with half maximal inhibitory concentration (IC50) values of 28.24±0.97 μg/ml and 92.31±1.22 μg/ml, respectively in comparison with the reference compound galantamine, which has IC50 values against the same enzymes of 5.21±0.07 μg/ml and 10.33±0.37 μg/ml, respectively. In addition, the VO, at a concentration of 20%, was effective against head lice, similar to benzyl benzoate, which resulted in 100% mortality. In addition, the VO completely inhibited the emergence of lice nits after 6 and 14 days. On the basis of the obtained results, S. capitata VO is a promising natural alternative to synthetic antipedicular and anticholinesterase drugs, which can be employed in drug development, and may lead to new candidates against head lice and neurodegenerative diseases

Variability of Chemical Compositions and Antimicrobial and Antioxidant Activities of Ruta chalepensis Leaf Essential Oils from Three Palestinian Regions

Introduction. Interest in essential oils was recently revived with their popularity increasing in medicine, pharmacy, and aromatherapy. This study was performed to identify the chemical compositions of the essential oil of Ruta chalepensis growing wildly in three regions in Palestine and to assess and compare their antimicrobial and antioxidant activities. Methods. Identification of the essential oil was performed by gas chromatography coupled with mass spectrometry (GC-MS). Antimicrobial activity was tested against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Methicillin-Resistant Staphylococcus aureus, and Candida albicans by using minimum inhibitory concentration (MIC) assay, while antioxidant activity was analyzed by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Results. The essential oils of R. chalepensis from Jerusalem and Hebron regions have almost identical components; the major compounds identified were linalyl acetate and β-linalool; these essential oils exerted potential antioxidant and antibacterial activities. On the other hand, the major components of the plant essential oil from Jenin region were 2-undecanone and 2-nonanone, which exhibited potential antifungal activity. Conclusions. The phytoconstituents and antioxidant and antimicrobial properties of the essential oil of R. chalepensis from different regions in Palestine were established in this study. The obtained results indicate possible applications for R. chalepensis in the treatment of various infectious and noninfectious diseases

Alarmingly high prevalence of high-risk drug use among palestinian males: a cross-sectional study

Abstract Background The unique socioeconomic context in Palestine, characterized by political and economic tensions, creates conditions that facilitate the spread of illicit drug use among Palestinians. This paper presents findings from a 2017 survey of high-risk drug use (HRDU) among males in four regions in Palestine: the West Bank (north, middle, and south) and the Gaza Strip. These findings are essential for developing effective policies to respond to the increasing use of drugs among Palestinians. Methods Eligible participants were males aged 15 years and above who used at least one drug other than non-synthetic hashish or marijuana during the previous week. Participants underwent a face-to-face interview and had their drug use verified by urinalysis. Data were collected using respondent-driven sampling and data were analyzed using the successive sampling estimator. Multivariate regression analysis was conducted to examine factors associated with ever seeking rehabilitation services for illicit drug use in the West Bank and the Gaza Strip. Results A total of 400 males who use drugs were sampled in Gaza, plus 299 in the south, 300 in the north, and 299 in the middle region of the West Bank. It is estimated that there are 26,500 male HRDUs in Palestine comprising 1.8% of the male population aged 15 and above. Findings indicate that polydrug use is a serious issue in Palestine, especially in the West Bank, and that synthetic marijuana is prevalent among teenagers and young adults. Conclusions Palestine must strengthen its national efforts to scale up harm reduction and treatment and care options for people suffering from drug use disorders, especially those involved in polydrug use. Additional measures are needed to prevent substance use among children and youth, support the families of people who use drugs, and ensure the continuity of HRDU services during emergencies