Phytofabrication, characterization of silver nanoparticles using Hippophae rhamnoides berries extract and their biological activities.

Introduction: Fabrication of plant-based metal nanoparticles has yielded promising results, establishing this approach as viable, sustainable, and non-toxic in the biomedical sector for targeted drug delivery, diagnostic imaging, biosensing, cancer therapy, and antimicrobial treatments. Methods: The present work demonstrates the suitability of Hippophae rhamnoides berries for the instant green synthesis of silver nanoparticles to check their antioxidant, lipid peroxidation, and antimicrobial potential. The preliminary characterization of Hippophae rhamnoides-mediated AgNPs was validated by monitoring the color shift in the solution from pale yellow to reddish brown, which was further confirmed by UV-vis spectroscopy and the plasmon peaks were observed at 450 nm. Field Emission Scanning Electron Microscopy (FESEM) and X-ray diffraction (XRD) were used to evaluate the surface topography and structure of AgNPs. Herein, the antioxidant potential of synthesized AgNPs was investigated using DPPH free radical assay and the antimicrobial efficacy of similar was checked against E. coli and S. aureus by following MIC (minimum inhibitory concentration) and MBC (Minimum bactericidal concentration) assay. Along with the inhibitory percentage of lipid peroxidation was analysed by following TBARS (Thiobarbituric acid reactive species) assay. Results & discussion: The results revealed that the AgNPs were spherical in shape with an average size distribution within the range of 23.5-28 nm and a crystalline structure. Negative zeta potential (-19.7 mV) revealed the physical stability of synthesized AgNPs as the repulsive force to prevent immediate aggregation. The bioactive functional moieties involved in reducing bulk AgNO3 into AgNPs were further validated by FTIR. TBARS was adapted to test lipid peroxidation, and Hippophae rhamnoides-mediated AgNPs showed a 79% inhibition in lipid peroxidation compared to Hippophae rhamnoides berries extract as 65%. Furthermore, the antibacterial tests showed 37 ± 0.01 mm and 35 ± 0.0132 mm, zones of inhibition against E. coli MTCC 1698 and S. aureus MTCC 3160 with MIC and MBC values of 1 mg/mL, respectively.

6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

BACKGROUND: Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. METHODS: A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1ß (IL-1ß), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. RESULTS: The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. CONCLUSIONS: The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.

Pirfenidone ameliorates ANIT-induced cholestatic liver injury via modulation of FXR, NF-кB/TNF-α, and Wnt/GSK-3ß/ß-catenin signaling pathways.

Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3ß/ß-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/ß-catenin signaling pathways.

Cross-Sectional Survey to Assess Dental Students' Perception of the Utilization of a Case Difficulty Assessment Form during Various Stages of Root Canal Therapy.

Background: Several endodontic difficulty assessment forms are available to help dental students and general dentists estimate the difficulty of the case before initiating the endodontic treatment. Objectives: This study aimed to assess if the American Association of Endodontics (AAE) case difficulty assessment form affects the dental student's perception of the difficulty encountered while performing root canal treatment (RCT). Materials and Methods: This was a cross-sectional online survey. After obtaining IRB approval, an electronic questionnaire was sent to dental students enrolled in the 4th and 5th years at King Saud University (KSU) and King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia. The questionnaire was divided into informed consent, demographic data, the use of the AAE case assessment form, RCT steps, diagnosis, local anesthesia administration, tooth isolation, and endodontic procedure. Results: A total of 195 dental students participated in the study. There were 101 (52%) females, and 139 (71%) were from KSAU-HS. A positive association was found between students who used the AAE assessment form and who did not with their ability to reach the correct diagnosis (p=0.005), tooth isolation (p=0.03), and endodontic procedure difficulty score (p=0.018). Conclusion: The use of the AAE form by dental students enabled them to differentiate between complicated and uncomplicated cases, thus lowering the difficulty encountered during RCT.

Synchronized Glioma Insights: Trends, Blood Group Correlations, Staging Dynamics, and the Vanguard of Liquid Biopsy Advancements.

BACKGROUND: Gliomas are the most frequent, heterogeneous group of tumors arising from glial cells, characterized by difficult monitoring, poor prognosis, and fatality. Tissue biopsy is an established procedure for tumor cell sampling that aids diagnosis, tumor grading, and prediction of prognosis. MATERIALS AND METHODS: We studied and compared the levels of liquid biopsy markers in patients with different grades of glioma. Also, we tried to prove the potential association between glioma and specific blood group antigens. RESULTS: 78 patients were found, among whom the maximum percentage with glioblastoma had blood group O+ (53.8%). The second highest frequency had blood group A+ (20.4%), followed by B+ (9.0%) and A- (5.1%), and the least with O-. Liquid biopsy biomarkers included Alanine Aminotransferase (ALT), Lactate Dehydrogenase (LDH), lymphocytes, Urea, Alkaline phosphatase (AST), Neutrophils, and C-Reactive Protein (CRP). The levels of all the components increased significantly with the severity of the glioma, with maximum levels seen in glioblastoma (grade IV), followed by grade III and grade II, respectively. CONCLUSION: Gliomas have significant clinical challenges due to their progression with heterogeneous nature and aggressive behavior. A liquid biopsy is a non-invasive approach that aids in setting up the status of the patient and figuring out the tumor grade; therefore, it may show diagnostic and prognostic utility. Additionally, our study provides evidence to prove the role of ABO blood group antigens in the development of glioma. However, future clinical research on liquid biopsy will improve the sensitivity and specificity of these tests and confirm their clinical usefulness to guide treatment approaches.

Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway.

BACKGROUND: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally. OBJECTIVE: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers. METHODS: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1ß (IL-1ß), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets. RESULTS: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1ß, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol. CONCLUSION: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.

Knowledge and Attitude Toward Otitis Externa: A Saudi Arabian Perspective.

Objectives: This study intended to assess the level of awareness and attitude toward otitis externa (OE) and specific limitations that counter the attempts to uplift the understanding and notion related to OE among the general population of Saudi Arabia. Methods: A cross-sectional quantitative study using a questionnaire was done via Google Forms between May 2023 and July 2023. The scoring method was used to determine the participant's awareness or attitude; participants who scored >50% were considered aware or to have a good attitude. Results: Approximately 52.2% had a good attitude toward the OE, and majority were willing to visit healthcare professionals (81%) to provide care and receive proper education during office visits (80.1%). Of all the participants, 69%, 33.4%, and 30.8% suggested that a lack of awareness, cost, and health insurance, respectively, might prevent patients from seeking a healthcare professional. Only 10.9% of participants demonstrated good awareness (score >13) of outer ear inflammation. Conclusion: The findings indicate a poor level of awareness regarding OE, and a positive attitude toward seeking healthcare, with the majority recommending professional visits and relying on healthcare professionals for information.

Autosomal Recessive Spastic Paraplegia and Psychomotor Retardation With or Without Seizures: A Case Report From Saudi Arabia.

Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a rare neurodevelopmental disorder associated with autosomal recessive mutations in the HACE1 gene. This case report presents the clinical features and genetic analysis of an 11-month-old girl and her sister with SPPRS, making it the third reported case in the Middle East and the second in Saudi Arabia. The patient exhibited hypotonia, global developmental delay, speech delay, swallowing difficulties, and recurrent respiratory infections. A homozygous pathogenic variant in the HACE1 gene (p.R664*) was identified through genetic analysis, confirming the diagnosis of SPPRS. This case report emphasizes the importance of considering variations in clinical presentation, especially in rare disorders where only a few cases are reported. Further research and case studies are needed to better understand the complete phenotypic spectrum of SPPRS and its complications.

Normal sonographic measurements for kidney dimensions in Saudi adult population: A cross-sectional prospective study.

BACKGROUND: The use of ultrasound-based measurements to determine renal size has proven valuable in the diagnosis of renal function and associated disorders. The dimensions of the abdominal organs are affected by an individual's body age, height, sex, and weight. The objective of this study was to establish the standard sonographic parameters for renal dimensions and to determine the correlation between body measurements and renal dimensions in a population of healthy adults residing in Jazan City, Saudi Arabia. METHODS: The present study was a prospective study conducted at a single center located in Jazan City from February to August 2022. Ninety-five participants underwent abdominal ultrasonography. The process of measuring renal size through sonography entails the measurement of various dimensions of the kidney, such as renal length, width, and thickness. The demographic information of the participants, including their sex, age, height, and weight, was documented. All analyses were performed using Statistical Package for the Social Sciences v27 software. RESULTS: The dimensions of the right kidney, specifically the length, width, and thickness, had mean value of 9.79 centimeters (cm), 5.09 cm, and 4.10 cm, respectively. The left kidney had mean dimensions of 10.1 cm, 5.09 cm, and 4.10 cm for length, width, and thickness, respectively. The left kidney was larger than the right kidney. Furthermore, male participants exhibited larger kidney measurements than their female counterparts did. A noteworthy positive correlation was observed between the thickness of the left kidney and sex, whereas no significant correlations were found with age, weight, or height. CONCLUSION: The current study revealed that the kidney dimensions were observed to be larger in males as compared to females. The research findings indicate that there is no significant correlation between kidney dimensions and various demographic factors, such as age, height, weight, and sex. In addition, this study provides reference tables for further use.

Malaria during COVID-19 Travel Restrictions in Makkah, Saudi Arabia.

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.

Knowledge, Attitude, Motivators, and Barriers to Blood Donation Among Adults in Al-Qunfudah Governorate, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Blood transfusion is one of the most important aspects of managing patients with a variety of medical disorders like thalassemia and sickle cell anemia. Despite this fact, many Saudis hesitate to donate blood and do not know whether blood banks need blood. OBJECTIVES: To evaluate the knowledge, attitude, motivators, and barriers to blood donation among adults in Al-Qunfudah governorate, Saudi Arabia. METHODS: A descriptive cross-sectional study was performed on a convenience sample of 416 adults living in Al-Qunfudah governorate and its dependence, using an online self-administered questionnaire. The obtained data were analyzed statistically using SPSS version 21 (IBM Corp., Armonk, New York, USA). RESULTS: Among 416 respondents, exactly 232 (55.8%) had overall good knowledge regarding blood donation, and 334 (80.3%) positively perceived it. The best knowledge about blood donation was detected among those aged 21-24 years (p = 0.012), males (p = 0.008), university-educated (p = 0.048), having a government job (p = 0.001), and having a history of donating blood (p = 0.001). The motivators included religious motives (88.2%, n = 367), feelings of self-satisfaction (63.2%, n = 263), and restoring blood circulation (56.7%, n = 236). Barriers to blood donation were fear of being infected (27.6%, n = 115), needle phobia (23.6%, n = 98), fear of general weakness (22.8%, n = 95), didn't know how to donate (16.8%, n = 70), and fear of seeing blood (13.2%, n = 55). CONCLUSION: Although adults in the Al-Qunfudah governorate of Saudi Arabia had positive attitudes toward blood donation, they possessed inadequate knowledge about it. Being younger, male, university-educated, having government jobs, and having a past history of donating blood were factors associated with good knowledge of blood donation. The most common motivators were religious, financial, and maintaining health. However, fear of infection, needle sticks, fear of pain, and hemophobia were the recorded barriers. Public health education is recommended to tackle public concerns regarding blood donation and present its benefits.

Utilizing Artificial Intelligence Among Patients With Diabetes: A Systematic Review and Meta-Analysis.

Diabetes mellitus, a condition characterized by dysregulation of blood glucose levels, poses significant health challenges globally. This meta-analysis and systematic review aimed to evaluate the effectiveness of artificial intelligence (AI) in managing diabetes, underpinned by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review scrutinized articles published between January 2019 and February 2024, sourced from six electronic databases: Web of Science, Google Scholar, PubMed, Cochrane Library, EMBASE, and MEDLINE, using keywords such as "Artificial intelligence use in medicine, Diabetes management, Health technology, Machine learning, Diabetic patients, AI applications, and Health informatics." The analysis revealed a notable variance in the prevalence of diabetes symptoms between patients managed with AI models and those receiving standard treatments or other machine learning models, with a risk ratio (RR) of 0.98 (95% CI: 0.88-1.08, I2 = 0%). Sub-group analyses, focusing on symptom detection and management, consistently showed outcomes favoring AI interventions, with RRs of 0.97 (95% CI: 0.87-1.08, I2 = 0%) for symptom detection and 0.97 (95% CI: 0.56-1.57, I2 = 0%) for management, respectively. The findings underscore the potential of AI in enhancing diabetes care, particularly in early disease detection and personalized lifestyle recommendations, addressing the significant health risks associated with diabetes, including increased morbidity and mortality. This study highlights the promising role of AI in revolutionizing diabetes management, advocating for its expanded use in healthcare settings to improve patient outcomes and optimize treatment efficacy.

Retrocaval Ureter With Ureteric Stones: A Case Report.

The retrocaval ureter is an uncommon anomaly where the ureter passes behind the inferior vena cava. Open surgery had been the gold standard for treatment. We are presenting a case of the retrocaval ureter with ureteral calculi, which was effectively managed by open surgery. A 27-year-old male presented with a nine-month history of flank pain. He had no history of chronic illnesses. Physical examinations and laboratory findings were within normal. A computed tomography (CT) scan was done to confirm the diagnosis of retrocaval ureter with ureteral stones. The subcostal incision was made. Then, the proximal and lower ureter was transected at the point where it went retrocaval. The stones were extracted; then, watertight anastomosis was done. Ultrasound used for the follow-up of the patient for six months showed no hydronephrosis. Retrocaval ureteral may have no symptoms or be linked to nonspecific symptoms. The diagnosis of the retrocaval ureter is frequently delayed. Surgical management is utilized in the majority of cases.

Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

A Selective Gas Chromatography-Tandem Mass Spectrometry Method for Quantitation of Ethylene and Diethylene Glycol in Paediatric Syrups.

Ethylene Glycol (EG) and diethylene Glycol (DEG) are two contaminants known to cause various human health problems. These glycols might be present in drug syrups that are based on glycerol, sorbitol, or polyethylene glycol. In late 2022, several batches of cough, antipyretics, and antihistamine syrups were reported to contain toxic levels of EG and DEG in multiple countries; this incident concerned the World Health Organization (WHO). From an analytical perspective, several methods of glycols analysis in pharmaceuticals have been reported in the literature, with the majority being dedicated to raw material analysis. This study aims to develop a selective method capable of evaluating a wide range of paediatric syrups in order to assess the safety of commercially available paediatric syrups currently distributed in the local market. This research introduces a method for determining glycols utilizing gas chromatography-tandem mass spectrometry (GC-MS/MS), which offers significantly higher selectivity than conventional single quadrupole gas chromatography-mass spectrometry (GC-MS). The developed method meets the current International Council for Harmonisation (ICH) guidelines for validation. The absence of any interfering peaks in both the unspiked sample of promethazine syrup and the reference standard solutions proved the method's selectivity. Furthermore, 2,2,2-trichloroethanol was used as an internal standard, and a new GC-MS/MS method was developed to analyze it. The calibration curves for EG and DEG were linear within the selected concentration range of 1-10 µg/mL. The detection limit for both EG and DEG was 400 ng/mL, while the quantification limit was 1 µg/mL. Recovery values for both EG and DEG met the accuracy acceptance criterion. Thus, the developed method proved to be efficient and accurate for determining EG and DEG levels in suspected contaminated syrups.

UHRF1 poly-auto-ubiquitination induced by the anti-cancer drug, thymoquinone, is involved in the DNA repair machinery recruitment.

DNA methylation is one of the most important epigenetic mark involved in many physiologic cellular processes and pathologies. During mitosis, the transmission of DNA methylation patterns from a mother to the daughter cells is ensured through the action of the Ubiquitin-like, containing PHD and RING domains, 1/DNA methyltransferase 1 (UHRF1/DNMT1) tandem. UHRF1 is involved in the silencing of many tumor suppressor genes (TSGs) via mechanisms that remain largely to be deciphered. The present study investigated the role and the regulation of UHRF1 poly-ubiquitination induced by thymoquinone, a natural anti-cancer drug, known to enhance or re-activate the expression of TSGs. We found that the auto-ubiquitination of UHRF1, induced by TQ, is mediated by reactive oxygen species, and occurs following DNA damage. We demonstrated that the poly-ubiquitinated form of UHRF1 is K63-linked and can still silence the tumor suppressor gene p16INK4A/CDKN2A. We further showed that TQ-induced auto-ubiquitination is mediated via the activity of Tip60. Since this latter is known as a nuclear receptor co-factor, we investigated if the glucocorticoid receptor (GR) might be involved in the regulation of UHRF1 ubiquitination. Activation of the GR, with dexamethasone, did not influence auto-ubiquitination of UHRF1. However, we could observe that TQ induced a K48-linked poly-ubiquitination of GR, probably involved in the proteosomal degradation pathway. Mass-spectrometry analysis of FLAG-HA-tagged UHRF1 identified UHRF1 partners involved in DNA repair and showed that TQ increased their association with UHRF1, suggesting that poly-ubiquitination of UHRF1 is involved in the DNA repair process. We propose that poly-ubiquitination of UHRF1 serves as a scaffold to recruit the DNA repair machinery at DNA damage sites.

Recent Patterns and Assessment of Long-term Complications followi ngSARS-CoV-2 Infection and Vaccination in the Context of Diabet esPrevalence among Blood Donors.

BACKGROUND: Much increasing evidence has suggested that long-term complications post vaccination of SARS-CoV-2 experience a wide range of complication including diabetes. The risk and burden of type 1 diabetes is extensively reported, but type 2 diabetes mellitus (T2D) has yet to be characterized. To address this gap, we aimed to examine trends of long-term complications post SARS-CoV-2 infection and vaccination in diabetes incidence among the Saudi population. METHODS: In this cross-sectional hospital-based study, we analyzed the blood profile of first-time blood donors from the University Hospital of King Abdulaziz University, Jeddah. Saudi Arabia. Various blood parameters, HbA1c was measured in the month of May 2023. All the donors were non-diabetic and were never diagnosed with T2D before the current blood donation. 203 healthy subjects donated their blood, out of which 104 had abnormally high HbA1c tending towards diagnosis of T2D and 99 had with blood profiles. The study followed the STROBE reporting guidelines. RESULTS: Out of 203 donors 104 (male 50(48.1%), female 54(51.9%)) were diagnosed with increased HbA1c (8.24 in males) compared to 7.61 of HbA1c in females. 35.6% were above ˃65 years, with 52.9% with O+ from the ABO blood group. Liver functions indicated significant p˂0.05, 0.04, increased amount of GGT (46.47 U/L), Alkaline phosphatase (99.93 ±64.26 uL) respectively in HbA1c elevated donors KFT represented significant p˂0.05, 0.02 elevated levels of urea (6.73 ±5.51 mmol/L), creatinine (129.97 ±195.17 umol/L) respectively along with elevated values of Lactate dehydrogenase (LDH) (263.72± 196.70 uL) and triglycerides (1.66 ±0.74mmol/L) when compared to normal value of HbA1c donors. DISCUSSION: In the present cross-sectional study, significant increase in HbA1c, trending towards increased cases of T2D post SARS-CoV-2 infection and vaccination. Males are much affected compared to females. Further maximum number of cases were from donors above the age of 65 years with altered partial LFT (GGT, Alkaline phosphatase), KFT (urea, creatinine), lipid profile (TG) and LDH in post SARS-CoV-2 and vaccination blood donors. CONCLUSION: Increase in HbA1c in 50% of donors, irrespective of gender, is an alarming figure for health authorities, with altered LFT, KFT and LDH tests and, in the near future, may increase the incidence of T2D. Large-scale population-based studies are required to prevent future incidences of T2D in young children who will be vaccinated.

Modulation of the crosstalk between Keap1/Nrf2/HO-1 and NF-κB signaling pathways by Tomatidine protects against inflammation/oxidative stress-driven fulminant hepatic failure in mice.

Fulminant hepatic failure (FHF) is the terminal phase of acute liver injury, which is characterized by massive hepatocyte necrosis and rapid hepatic dysfunction in patients without preexisting liver disease. There are currently no therapeutic options for such a life-threatening hepatic failure except liver transplantation; therefore, the terminal phase of the underlying acute liver injury should be avoided. Tomatidine (TOM), asteroidal alkaloid, may have different biological activities, including antioxidant and anti-inflammatory effects. Herein, the lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF mouse model was established to explore the protective potential of TOM and the underlying mechanisms of action. TOM pretreatment significantly inhibited hepatocyte necrosis and decreased serum aminotransferase activities in LPS/D-GalN-stimulated mice. TOM further increased the level of different antioxidant enzymes while reducing lipid peroxidation biomarkers in the liver. These beneficial effects of TOM were shown to be associated with targeting of NF-κB signaling pathways, where TOM repressed NF-κB activation and decreased LPS/D-GalN-induced TNF-α, IL-6, IL-1ß, and iNOS production. Moreover, TOM prevented LPS/D-GalN-induced upregulation of Keap1 expression and downregulation of Nrf2 and HO-1 expression, leading to increased Nrf2-binding activity and HO-1 levels. Besides, TOM pretreatment repressed LPS/D-GalN-induced upregulation of proliferating cell nuclear antigen (PCNA) expression, which spared the hepatocytes from damage and subsequent repair following the LPS/D-GalN challenge. Collectively, our findings revealed that TOM has a protective effect on LPS/D-GalN-induced FHF in mice, showing powerful antioxidant and anti-inflammatory effects, primarily mediated via modulating Keap1/Nrf2/HO-1 and NF-κB/TNF-α/IL-6/IL-1ß/iNOS signaling pathways.

The role of molecular imaging in detecting fibrosis in Crohn's disease.

Fibrosis is a pathological process that occurs due to chronic inflammation, leading to the proliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM). The process of long-term fibrosis initiates with tissue hypofunction and progressively culminates in the ultimate manifestation of organ failure. Intestinal fibrosis is a significant complication of Crohn's disease (CD) that can result in persistent luminal narrowing and strictures, which are difficult to reverse. In recent years, there have been significant advances in our understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in inflammatory bowel disease (IBD). Significant progress has been achieved in the fields of pathogenesis, diagnosis, and management of intestinal fibrosis in the last few years. A significant amount of research has also been conducted in the field of biomarkers for the prediction or detection of intestinal fibrosis, including novel cross-sectional imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). Molecular imaging represents a promising biomedical approach that enables the non-invasive visualization of cellular and subcellular processes. Molecular imaging has the potential to be employed for early detection, disease staging, and prognostication in addition to assessing disease activity and treatment response in IBD. Molecular imaging methods also have a potential role to enabling minimally invasive assessment of intestinal fibrosis. This review discusses the role of molecular imaging in combination of AI in detecting CD fibrosis.