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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

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Coronary Artery Patterns in Diabetic Patients Undergoing Diagnostic Coronary Angiography-Data from a Major Cardiac Center in Yemen

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World Journal of Cardiovascular Diseases 2024年第4期14卷 268-281页

作者： Mohammed M. al-Kebsi Yehia al-Ezzy Amatasamad al-Tanobi Ayman A. Mohammed Department of Cardiology Faculty of Medicine and Health Sciences Sana&#8217a University Sana&#8217a Yemen Cardiac Center Al-Thawra Modern General Hospital Sana&#8217a Yemen

Background: Diabetes mellitus (DM) is independently associated with an increased risk of cardiovascular mortality and morbidity, including coronary artery disease (CAD). CAD is a shared burden disease and the leading cause of death in developed and developing countries. We aimed to assess the angiographic patterns of coronary arteries in patients with DM in a developing country (Yemen) as the first study. Methods: This study is a cross-sectional, prospective, observational study that includes a total of 250 patients who were admitted for elective diagnostic coronary angiography. Results: 96 (38.4%) patients were diabetics;68% were male;mean age was 57 ± 11 years. The incidence of three-vessel disease was 31.2% of patients. Considering the severity of lumen occlusion, (11.2%) of patients had non-significant lesions, (37.6%) of patients had significant lesions, and (32%) had total occlusive lesions. Lesions were of LAD in 76%, RCA in 60%, and LCX in 52% of the population. Among diabetics, two and 3-vessel diseases (33.3% vs. 20.8% & 50% vs. 19.5%, P = 0.001), left main lesion (10.4% vs. 2.6%, P = 0.012), significant stenosis (41.7% vs. 35.1%, P = 0.032), total occlusion of coronary arteries (43.8% vs. 19.5%, P = 0.032) and type C lesion (66.7% vs. 35.1%, P = 0.010) were more frequent than non-DM patients. Conclusion: The burden of significant and severe coronary lesions is more common among DM, which may be the major cause of morbidity and mortality of DM in developing countries.

关键词： Diabetes Mellitus Coronary Artery Diseases Coronary Angiography

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The Protective Effect of Moringa oleifera Leaves Extract on Paracetamol Hepatotoxicity in Male Rats

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Journal of Biomedical Science and Engineering 2024年第3期17卷 72-82页

作者： Reham M. al-Sultan Noorah Saleh al-Sowayan Department of Biology College of Science Qassim University Buraydah Saudi Arabia

In recent years, there has been an increase in concern regarding the effects of paracetamol poisoning on liver tissues, particularly when consumed in large amounts. Some studies have estimated that paracetamol is involved in 56% of acute liver diseases, whereas 0.4% of paracetamol overdose cases result in fatal-ity. In this study, the effects of Moringa oleifera on paracetamol toxicity in the liver were explored. It has been demonstrated that Moringa oleifera is highly nu-tritious, contains bioactive molecules, and is therapeutically beneficial. Many studies have shown that Moringa oleifera leaves possess a wide range of biologi-cal properties, including antioxidant, tissue protection, analgesic, antihyperten-sive, and immunomodulatory activities. This study highlights the protective role of Moringa oleifera on handling possible paracetamol hepatotoxicity in male rats. .

关键词： Moringa oleifera Paracetamol Hepatotoxicity Oxidative Stress

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Portraying Diabetic Foot Ulcers: Comparative Evaluation of Diabetic Foot Infections versus Diabetic Foot Ulcers

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Advances in Infectious Diseases 2024年第2期14卷 297-309页

作者： Jamal Wadi al Ramahi Leen Sharqawi Sarah al-Najafi Eman Awwad Haya M. al-Obaidi Abdel Hafez Mohammad Sara Nofal Dina Riyadh al-Janabi Ibrahim Zuhair Hamza Jamal al-Masaeid Mohammed al-Ithawi Dina Rasheed Bellal O. al-Far Osama al-Izi Qutaiba al-Bustanji School of Medicine The University of Jordan Amman Jordan Department of the Internal Medicine The Specialty Hospital Amman Jordan Department of Pharmacy The Specialty Hospital Amman Jordan Department of the Medical Al Khalidi Hospital Amman Jordan Department of Pharmacy Jordan Hospital Amman Jordan Department of Internal Medicine Jordan Hospital Amman Jordan Department of General Surgery Jordan Hospital Amman Jordan

Background: Confusion often arises in caring for diabetic foot infections and ulcers, especially with antimicrobials;we aim to shed light on this entity and alert healthcare workers to its stewardship. Methods: Records were reviewed between February 2016 and September 2023. Data for patients diagnosed with diabetes and foot ulcers, infected or not, were examined following ICD 9 search terms. Records for patients were included if they were prediabetic/diabetic adults with foot ulcers, more than 18 years old, and on antidiabetic treatment. Patients were excluded if they insulin resistant, with normal HgbA1c levels, wheel-chair dependent, bed-bound, non-diabetic patients, diabetic patients who had vascular lower limb surgery earlier to ulcers, diabetic patients who had aortocoronary bypass, deep venous thrombosis within six months, malignancy, and severe clinical depression. A modified IWGDF/IDSA guidelines definitions for DFI and DFU was considered. Statistical analysis was done using R programming. Statistical methods were employed as appropriate, and a significant P-value was considered for P Results: Most characteristics were well balanced between DFI and DFU, on imaging osteomyelitis and tissue swelling were significantly more in DFI. Endovascular radiological procedures showed angiograms to be considerably more in DFI, while angioplasty was more in DFU, in addition to smoking. Bacteremia was uncommon, and swab cultures were mostly polymicrobial in both ulcers;no clear association with blood bacteria was detected with the polymicrobial growth, though few were concordant. Antimicrobials prescribed for both ulcers were not statistically different except for carbapenems, which were more in DFI (P Conclusion: Attention should be paid to best practices while caring for diabetic ulcers. These include swab culture interpretations, the use of antimicrobials, and plan management according to DFI or DFU to utilize either local care or combination with antimicrobials.

关键词： Diabetic Foot Ulcers Diabetic Limb Amputation Antimicrobials Stewardship Broad-Spectrum Antimicrobials in Diabetic Foot Ulcers

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Hydroxychloroquine: A Safe, Effective and Inexpensive Maintenance Therapy for Chronic Spontaneous Urticaria

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International Journal of Clinical Medicine 2024年第6期15卷 225-232页

作者： Kamel El-Reshaid Shaima al-Bader Abdulla al-Refaee Department of Medicine Faculty of Medicine Kuwait University Kuwait Kuwait Asad al-Hamad Dermatology Center Ministry of Health Kuwait Kuwait

Background: Chronic spontaneous urticaria (CSU) is an autoimmune skin disorder that lasts for >6 weeks and may last for years. It is a disabling skin disease that impairs quality of life. Set-up treatment with antihistamines, immunosuppressives, immune modulators and lately Omalizumab are expensive or have significant side effects. In this retrospective study, we describe our experience with the use of hydroxychloroquine (HCQ) as a maintenance therapy for those with severe forms of CSU after Corticosteroids (C) induction phase. Patients and Methods: 16 adult patients (aged 44 ± 7) with severe CSU for 5 ± 1 months, were included in the study. Eight patients had attacks of angioneurotic oedema. Their previous treatments were antihistaminic and short-courses of C. Results: After 2 weeks of remission with C and HCQ 200 mg twice daily, the dose of C was tapered down and discontinued by the end of the first month. The seven days Urticaria Activity Score decreased from 30 ± 3 to 6 ± 1 by the first month and remained low at 3 ± 1 by the end of 2 years of follow-up. Moreover, IgE levels and CRP had similar trends. Remission persisted after 37 ± 9 months of follow-up. Conclusion: HCQ is a safe, efficacious and inexpensive drug for the treatment of CSU.

关键词： Autoimmune Disease Chronic Spontaneous Urticaria Corticosteroids Hydroxychloroquine Omalizumab

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Evaluation of Textured Concrete as an alternative for Stone as a Cladding Material

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Journal of Civil Engineering and Architecture 2024年第4期18卷 199-205页

作者： Mahmmoud al-Subieh Department of Architecture Amman Al-Ahlyah UniversityAmman 19328Jordan

along with the increasing demand on exterior wall cladding as a protective cover for the interior elements and an indicator for modernity and architectural innovation,comes the need to develop new cladding materials that can replace the old ones and overcome their *** paper discusses the possibility of replacing stone by textured concrete as a cladding material in order to overcome the main challenges faced stone cladding by comparing them *** comparison was made based on the main requirements of the cladding materials namely:economic,environmental,social,functional and structural aspects.

关键词： Textured concrete stone cladding

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Pre-autism:Advancing early identification and intervention in autism

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World Journal of Clinical Cases 2024年第34期12卷 6748-6753页

作者： Mohammed al-Beltagi Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511Egypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671Bahrain

Autism spectrum disorder(ASD)is often diagnosed long after symptoms have become *** delay can make it difficult to provide early intervention,which can impact long-term *** concept of"pre-autism"highlights the phase before a formal diagnosis of ASD,providing an opportunity for earlier identification and intervention,which could be a turning point in ASD *** a previous article,we explored different ways of diagnosing pre-autism,including historical records,physical markers,laboratory tests,and radiological *** manuscript builds on that foundation by emphasizing the importance of early diagnosis and intervention in *** research advancements have clarified that ASD presentations can be complex,and individualized support strategies are *** significance of pre-autism lies in its potential to alter the trajectory of ASD through early detection and intervention despite challenges such as limited awareness and variability in symptom *** and diagnostic tools have shown promise as avenues for early detection,but it is essential to exercise caution and not rely too heavily on yet-tobe-established *** these challenges requires a collaborative effort to increase awareness,improve access to diagnostic tools,and foster inclusive ***,this manuscript calls for ongoing research,advocacy,and resource allocation to enhance early detection and intervention efforts,ensuring optimal outcomes for individuals on the autism spectrum.

关键词： Pre-autism Early diagnosis Children Intervention Biomarkers Autism spectrum disorder Individualized support Collaboration

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Validation of a Method for Characterization of Ethanol in Water by HS-GC-FID to Serve the Traceability of Halal Measurements

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Green and Sustainable Chemistry 2024年第2期14卷 17-28页

作者： Adel B. Shehata Abdulrahman R. al Askar Mohammed A. al Rasheed Abdulrahman M. al Zahrany Fahd A. al Kharraa Sowailem A. al Sowailem Chemistry Department/National Measurement and Calibration Center (NMCC) Saudi Standards Metrology and Quality Organization (SASO) Riyadh Kingdom of Saudi Arabia

The determination of the ethanol content in food products is of fundamental importance for Halal certification. In this work, an analytical method for the determination of ethanol in water by headspace gas chromatography with flame ionization detector (HS-GC-FID) has been developed and validated for the use in characterization of ethanol reference materials. The validation study was carried out in the linear calibration range 100 - 1500 mg/kg using the NIST SRM 2900, nominal 95.6%. The studied performance characteristics of the method were the limit of detection, LOD, the limit of quantification LOQ, selectivity, linearity, precision, recovery and bias. The validation results showed that the method is selective, precise, accurate and free from any significant bias. The LOD and LOQ were 1.27 and 3.86 mg/kg respectively and the estimated expanded uncertainty was 2% indicating that the method is fit for the purpose of certification of ethanol in water reference materials.

关键词： Ethanol HS-GC-FID Validation Linearity Precision Bias

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Impact of Migrant Populations on Tuberculosis Rates in Saudi Arabia: Assessing How Migration Patterns Affect TB Incidence and Control Measures: A Narrative Review

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Journal of Tuberculosis Research 2024年第3期12卷 165-181页

作者： Neda ali al Bati Medical and Clinical Affairs Rural Health Network Eastern Health Cluster Dammam Kingdom of Saudi Arabia

This research focuses on the effects of migration on the TB infection rate and its prevention in Saudi Arabia, which has a large number of expatriates from TB-affected countries. Despite, based on the current global statistics of TB occurrence, it is evident that the national incidence of TB has reduced from 10.55 per 100,000 in 2015 to 8.36 per 100,000 in 2019;despite this, there are still some difficulties because migrants bring new strains of Mycobacterium tuberculosis. Hindrances, including language barriers and perceived immigration status, hinder patients from seeking medical attention or doctors from diagnosing diseases. Each patient and each cultural group need special attention to public health, enhancing living circumstances, and health care support. Community participation, inclusion of TB control programs into functional healthcare facilities, and the functioning of TB programs need to be stressed to address TB issues. Considering the focus on social, economic, and cultural approaches, the country can make severe advancements in TB control and population protection. This holistic analysis is critical for a long-term effective strategy to combat TB in the Kingdom.

关键词： Kingdom Saudi Arabia (KSA) Tuberculosis (TB) Prevalence Migrants Control Measures

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Unilateral Choanal Atresia in Adults: A Case Series

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International Journal of Otolaryngology and Head & Neck Surgery 2024年第3期13卷 187-193页

作者： Sultan Kadasah Abdulaziz al Qahtani Ghalib al-Sayed Abdullah al Helali Saud aldhabaan Abdullah Musleh ali Asiry Mohammed Asiri Shahd Dlboh Adnan al-Malki Abdulsalam alqhtani Mohammed al-khulban Sahar al-Otaibi Department of Surgery College of Medicine University of Bisha Bisha Saudi Arabia Department of Otolaryngology Head and Neck Surgery Armed Forces Southern Region Hospital Khamis Mushait Saudi Arabia Department of Otolaryngology Head and Neck Surgery Abha Children&#8217s Hospital Abha Saudi Arabia Department of Surgery College of Medicine King Khalid University Abha Saudi Arabia Department of Otolaryngology Head and Neck Surgery Aseer Central Hospital Abha Saudi Arabia College of Medicine King Khalid University Abha Saudi Arabia

Choanal atresia (CA) is a rare occlusion of the posterior choanae. Unilateral cases have been reported more than bilaterally, and it’s more often right-sided in those patients. According to the literature, mixed bony-membranous atresia is the most common type. There is a high incidence of craniofacial and visceral anomalies associated with congenital choanal atresia. Therefore, investigation for associated congenital anomalies is an important step before the surgery. We report 2 cases of incidental finding of unilateral choanal atresia in a 21- and 17-year-old with nasal discharge being the only complaint in the former and nasal obstruction with headache in the latter. The patients were then scheduled for day-surgery as a case of choanal atresia for transnasal, endoscopic repair and posterior septectomy. The patients were discharged home on the same day with the absence of restenosis or other complications.

关键词： Choanal Atresia Nasal Obstruction Congenital Anomaly

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