Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice.

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.

Echinops Asteraceae extract guards against malathion-induced liver damage via minimizing oxidative stress, inflammation, and apoptosis.

Malathion (MAL) is one of the highly toxic organophosphorus (OP) compounds that induces hepatotoxicity. Echinops. ritro leaves extract (ERLE) is traditionally used in the treatment of bacterial/fungal infections. This study's goal was to investigate the potential of extracts from ERLE against hepatotoxicity induced by MAL in male albino rats. Four equal groups of forty mature male albino rats were created: The rats in the first group used as a control. The second group of rats received ERLE orally. The third group received MAL. ERLE and MAL were administered to the fourth group of rats. Six-week treatment groups were conducted. Using lipid peroxidation indicators [malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], apoptotic markers [Bcl-2 & caspase-3] and tumor necrosis factor alpha (TNF-α). Rats treated with MAL underwent a significant increase on MDA, ALT, AST, caspase-3 and TNF-α marker with a significant decrease in antioxidant markers [CAT, SOD, GPx] and Bcl-2. Histologically, MAL-treated group's liver sections displayed damaged hepatocytes with collapsed portions, pyknotic nuclei, vacuolated cytoplasm, and congested central veins. Ultra structurally, rat livers treated with MAL showed dilated cisternae of endoplasmic reticulum, swollen mitochondria with disrupted cristae, nuclei with disrupted chromatin content, multiple lysosomes, multiple vacuolations and a disrupted blood sinusoid. With rats treated with ERLE, these alterations were essentially non-existent. It is possible to conclude that ERLE protects against MAL hepatotoxicity, and that this protection is related, at least in part, to its antioxidant activities.

Angiotensin II Type 1 receptor blockade attenuates the neuropathological changes in the spinal cords of diabetic rats with modulation of nuclear factor erythroid 2-related factor 2/ heme oxygenase 1 system.

Peripheral and central neuropathies frequently complicate worldwide diabetes. Compared to peripheral neuropathy, central neuropathy didn`t gain a major research interest. Angiotensin II is reported to be involved in diabetic neuropathic pain but its role in the central pathological changes in the spinal cord is not clear. Here, we study the role of Losartan; an Angiotensin II receptor 1 (AT1) antagonist in suppression of the diabetes-induced changes in the spinal cord. Three groups of rats were applied; a negative control group, a streptozotocin (STZ) diabetic group, and a group receiving STZ and Losartan. After two months, the pathological alteration in the spinal cord was investigated, and an immunohistochemical study was performed for neuronal, astrocytic, and microglial markers; nuclear protein (NeuN), Glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adaptor molecule 1 (Iba1), respectively, and for an apoptosis marker; caspase-3, and the inflammatory marker; nuclear factor kappa B (NF-kB) signaling, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); physiological antioxidant system. The results showed that Losartan caused recovery of spinal cord changes, by inhibiting the microglial and astrocytic activation, suppressing neuronal apoptosis and NF-kB expression with activation of Nrf2/HO-1 (P<0.0005). It is suggested, herein, that Losartan can suppress diabetes-induced glial activation, inflammation, neuronal apoptosis, and oxidative stress in the spinal cord; the mechanisms that may underlie the role of AT1 antagonism in suppressing diabetic neuropathic pain.

Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma.

BACKGROUND: High-grade urothelial carcinoma either non-Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem. AIM: Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker. MATERIAL AND METHODS: Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers' expression in S-UBC. RESULTS: The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1. CONCLUSION: Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.

Impact of Escherichia coli, Candida non-albicans, and Trichomonas vaginalis on Semen Chemical and Functional Parameters: an In-Vitro Study.

BACKGROUND: Infertility is a worldwide medical issue in which infection is recognized to play a major role. Pathogens trigger various mechanisms that impact fertility, either directly by affecting the physiological indices of semen or indirectly by disrupting the process of spermatogenesis. In the current work, the effect of in-vitro cultivation of Escherichia coli (E. coli), Candida non-albicans (C. non-albicans), and Trichomonas vaginalis (T. vaginalis) (as the most frequently reported sexually transmitted infections) was assessed on the physiological functions of the spermatozoa and the chemical characteristics of the seminal fluid. METHOD: The semen samples were exposed to cultures of E. coli, C. non-albicans, and T. vaginalis. The study analyzed the changes in motility, agglutination, viability, DNA fragmentation index (DFI%), seminal pH, and biochemical parameters at 1/2, 1, 1.5, 2, 2.5, 3.5 and 4 hours. RESULTS: Incubation of the semen samples with E. coli resulted in a progressive increase in agglutination, pH, and nitrite. The seminal glucose and the sperm motility, on the other hand, were reduced. The sperm vitality and seminal protein remained unaffected. C. non-albicans induced three forms of agglutination (head-to-head, tail-to-tail, and head-to-tail), lowered pH values and decreased the sperm motility, but did not alter the seminal protein, glucose, nitrite, nor the spermatozoa viability at the different tested time intervals. T. vaginalis resulted in increased seminal protein, and reduced glucose, pH, and motility. It also induced minimal agglutination and caused unchanged nitrite and sperm viability. The DFI% was increased in all pathogens with the C. non-albicans showing the highest DNA fragmentation index. CONCLUSION: Urogenital infection with E. coli, C. non-albicans, or T. vaginalis is assumed to affect the quality of semen through DNA fragmentation, agglutination and altered seminal chemical microenvironment.

Assessment of tear film parameters post-treatment with commercial eyelid cleaning wipes: a pilot study.

AIM: To investigate the short-term effects of commercially available eyelid-cleaning wipes on film parameters. METHODS: This study enrolled 48 healthy participants aged 20-35y (both males and females). Clinical assessment included the Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear break-up time (NITBUT), tear meniscus height (TMH), and lipid layer pattern (LLP). Based on these initial results, participants were categorized as either non-dry eye or dry eye. Participants in each group were randomly allocated to either Blephaclean® or Systane® treatments. Changes in NITBUT, TMH, and LLP levels before and after lid wipe treatment were assessed. RESULTS: The dry eye group exhibited significantly higher OSDI scores and lower NITBUT and TMH levels than in the non-dry eye group (P<0.001). Following the application of eyelid wipes (Systane® wipes), dry eye subjects experienced a significant improvement in NITBUT levels (P=0.0014) compared to the non-dry eye individuals. Although the remaining participants showed a marginal increase in TMH and NITBUT levels, these changes did not achieve statistical significance (P>0.05). Similarly, the LLP levels were significantly improved with Systane® (P<0.001) post-treatment compared to individuals in the non-dry eye group. However, the dry eye subjects showed higher post-treatment LLP levels than the untreated group (P<0.02). CONCLUSION: The short-term effects of Systane® eyelid wipes on tear film parameters suggest their effectiveness in dry eye disease. Nonetheless, further exploration of their long-term impact is essential to justify their cost effectiveness and efficacy in treating both aqueous deficiency and evaporative dryness.

Evaluating the level of visual acuity to minimise false-positives in different colour vision tests.

CLINICAL RELEVANCE: Accurate colour vision assessment is important in clinical settings to minimise false-positive errors and enhance the reliability of diagnoses outcomes. BACKGROUND: Colour vision testing is valuable in assessing the visual system, particularly given the high proportion of individuals with poor vision. This study aimed to determine the minimum visual acuity level required to perform a colour-vision test without errors. METHODS: After fogging the right eyes of 52 healthy participants using plus lenses to 1.60 logMAR, vision was evaluated using Ishihara, Hardy - Rand - Rittler Standard Isochromatic, Waggoner Pseudo-isochromatic, City University, Waggoner Computerised, and Farnsworth D-15 tests. Participants then completed these tests at lower fogging degrees (in 0.1-logMAR intervals). The acuity at which 5% of the tested population was considered abnormal was determined. RESULTS: Significant differences were found in the average visual acuity required to perform colour vision tests without errors (p < 0.05). The Waggoner Computerized test required the highest average visual acuity among the tests utilised. The Farnsworth D-15 test yielded the highest logMAR values. No significant differences were observed between the Waggoner Pseudo-isochromatic test and Hardy - Rand - Rittler Standard Isochromatic, Ishihara, and Farnsworth D-15 tests (p > 0.05). Additionally, no significant differences were found between the Ishihara and Hardy - Rand - Rittler tests (p > 0.1) or between the Waggoner Computerized and City University tests (p = 0.11). Colour vision testing maintained an accuracy ≤ 1.0 logMAR with the Ishihara and Hardy - Rand - Rittler tests, 1.1 logMAR with the Waggoner Pseudo-isochromatic and Farnsworth D-15 tests, and 0.9 logMAR with the Waggoner Computerized and City University tests. CONCLUSIONS: Insights are provided into the visual acuity thresholds required for accurate colour vision testing, which can serve as a basis for future research and provide a reference for clinical practice in this field.

Malaria: biochemical, physiological, diagnostic, and therapeutic updates.

Background: Malaria has been appraised as a significant vector-borne parasitic disease with grave morbidity and high-rate mortality. Several challenges have been confronting the efficient diagnosis and treatment of malaria. Method: Google Scholar, PubMed, Web of Science, and the Egyptian Knowledge Bank (EKB) were all used to gather articles. Results: Diverse biochemical and physiological indices can mirror complicated malaria e.g., hypoglycemia, dyslipidemia, elevated renal and hepatic functions in addition to the lower antioxidant capacity that does not only destroy the parasite but also induces endothelial damage. Multiple trials have been conducted to improve recent points of care in malaria involving biosensors, lap on-chip, and microdevices technology. Regarding recent therapeutic trials, chemical falcipain inhibitors and plant extracts with anti-plasmodial activities are presented. Moreover, antimalaria nano-medicine and the emergence of nanocarrier (either active or passive) in drug transportation are promising. The combination therapeutic trials e.g., amodiaquine + artemether + lumefantrine are presented to safely counterbalance the emerging drug resistance in addition to the Tafenoquine as a new anti-relapse therapy. Conclusion: Recognizing the pathophysiology indices potentiate diagnosis of malaria. The new points of care can smartly manipulate the biochemical and hematological alterations for a more sensitive and specific diagnosis of malaria. Nano-medicine appeared promising. Chemical and plant extracts remain points of research.

Modulatory effects of Moringa oleifera leaf extract on sodium nitrate-induced experimental colitis via regulation of P53, Ki-67 and PCNA biomarkers.

BACKGROUND: Ulcerative colitis is a risk factor for colorectal carcinoma. Different mechanisms are related to colitis like apoptosis and hyperproliferation. Moringa oleifera leaves extract (MO) provides a promising option to overcome the risk. PURPOSE: To examine the colonic changes in a rat model of colitis induced by sodium nitrate (SN) and study the effects of MO. STUDY DESIGN: Eight adult male rats were allocated in each of the three group; control (distilled water), SN (100 mg/kg/day, orally via gastric gavage), and SN + MO (100 mg/kg/day, orally via gastric gavage). METHODS: Body weight was measured after the end of the experiment. Colonic homogenates were tested for levels of oxidative stress indicators. Immunohistochemistry for P53, PCNA and Ki-67 was performed. Fresh colon specimens were used for quantitative real-time PCR for assessment of P53, PCNA and Ki-67 gene expression. RESULTS: SN group revealed a significant decreased weight (p = 0.002). MDA and NO levels were higher with SN administration than with MO co-administration (p= 0.04, 0.01 respectively). GSH level was reduced in SN group (p = 0.02) and significantly increased with MO intake (p = 0.04). SN-induced colonic destructive changes were reversed with MO. P53, PCNA and Ki-67 levels of gene expression were reduced in SN + MO group than SN group (P = 0.007, 0.02, 0.001 respectively). CONCLUSION: MO protected the colonic mucosa against SN-induced changes regulating apoptosis, and cell proliferation.

Role of mesenchymal stem cells-derived exosomes on inflammation, apoptosis, fibrosis and telocyte modulation in doxorubicin-induced cardiotoxicity: A closer look at the structural level.

Cardiotoxicity induced by doxorubicin (Dox) is a major complication in cancer patients. Exosomes (Ex) derived from mesenchymal cells could be a promising therapeutic for various heart diseases. This study investigated the role of Ex in Dox-induced cardiotoxicity and its mechanistic insights, using Sacubitril/valsartan (S/V) as a reference drug widely recommended in heart failure management. The study involved 24 Wistar rats, divided into a control, Dox, Dox + S/V, and Dox + Ex groups. The rats were assessed for cardiac enzymes, inflammatory and oxidative stress markers. Immunohistochemical expression of caspase-1, nuclear factor erythroid 2-related factor 2 (NrF2), E-Cadherin, CD117/c-kit, and Platelet-derived growth factor-α (PDGFα) was evaluated. P53 and Annexin V were assessed by PCR. Histological examination was performed using hematoxylin and eosin and Sirius red stains. Ex ameliorated the adverse cardiac pathological changes and significantly decreased the cardiac enzymes and inflammatory and oxidative stress markers. Ex also exerted antifibrotic and antiapoptotic effect in heart tissue. Ex treatment also improved NrF2 immunohistochemistry, up-regulated E-Cadherin immune expression, and restored the telocyte markers CD117/c-kit and PDGFα. Ex can mitigate Dox-induced cardiotoxicity by acting as an anti-inflammatory, antioxidant, antiapoptotic, and antifibrotic agents, restoring telocytes and modulating epithelial mesenchymal transition. RESEARCH HIGHLIGHTS: Exosomes exhibit positive expression for CD90 and CD105 whereas showing -ve expression for CD 34 by flow cytometry. Exosomes restore the immunohistochemical expression of the telocytes markers CD117/c-kit and PDGFα. Exosomes alleviate myocardial apoptosis, oxidative stress and fibrosis.

Assessment of the proliferative and angiogenic effects of the synthetic cannabinoid (R)-5-fluoro ADB on human cerebral microvascular endothelial cells.

Objectives: The process of vascular formation, also known as angiogenesis, primarily relies on endothelial cell proliferation, migration, and invasion. In recent years, it has been discovered that synthetic cannabinoids (SCs) may potentially impact angiogenic processes within the body. We evaluated the impact of the synthetic cannabinoid (R)-5-Fluoro-ADB on the proliferation rate and angiogenesis in Human Cerebral Microvascular Endothelial Cells (hBMECs). Materials and Methods: hBMECs were treated with (R)-5-Fluoro-ADB and investigated for cell viability, migration rate, and tube-like structure formation. Furthermore, angiogenic-related proteins including Angopoitein-1 and -2, and Vascular Endothelial Growth Factors (VEGF) were examined on mRNA and protein levels. Results: The results showed a notable rise in the rate of proliferation (P-value<0.0001) of HBMECs induced by (R)-5-Fluoro-ADB. The angiogenic capacity of HBMECs was also enhanced between 0.001 µM to 1 µM (R)-5-Fluoro-ADB. Moreover, an increase in the levels of ANG-1, ANG-2, and VEGF mRNA and protein, as well as elevated phosphorylation rate of GSK-3ß, were observed across various concentrations of (R)-5-Fluoro-ADB. Conclusion: Our results suggest an innovative approach in pharmacology for addressing a range of conditions linked to angiogenesis. This approach involves precise targeting of both cannabinoid receptors type-1 and -2. To achieve this, specific agonists or antagonists of these receptors could be employed based on the particular characteristics of the diseases in question.

Microbiota-Parasite Interaction: Implication of Secretory Immunoglobulin A and P2X7 Receptor Signaling.

The microbiota community is composed of bacteria, fungi, viruses, and protists that exert symbiotic effects within the human body. Unlike microbiota, parasites are characteristically reliant on their hosts to thrive and flourish, producing toxic metabolites that agitate microbiota and disturb homeostasis. The proper management of parasitic infections addresses several important challenges related to low socioeconomic status and emergent resistance. Therefore, understanding the microbiota's role in interactions with hosts and parasites is crucial for managing parasite diseases with fewer economic and adverse effects associated with pharmaceutical interventions. The current review was divided into three sections. Section 1 focused on the mutual microbiota-host interaction through the purinergic P2X7 receptor (P2X7R) and secretory immunoglobulin A (SIgA). The P2X7R is an abundant intestinal cation channel that is crucial in mucosal immunity, facilitated by SIgA-mediated protection in both innate and adaptive immunity. This study demonstrated that microbiota continually "teach and train" host immunity to attain homeostasis via SIgA production (in T cell-independent and T cell-dependent pathways) and the purinergic receptor P2X7R. In addition, we discussed the potential of manipulating SIgA and P2X7R in immune therapies targeting parasitic infections. Section 2 exhibited parasite-microbiota (microbe-microbe) interactions wherein each can indirectly affect one another through physical and immunogenic alterations and directly via predation, bactericidal protein production, and overlapping of nutrient resources. Thus, microbe-microbe interactions appeared to be multifaceted and species-dependent. Section 3 showed the relationship between microbiota and specific parasites, and the promising role of probiotics. In this section, the review discussed examples of tissue, blood, gastrointestinal, genitourinary, and respiratory parasitic diseases, while highlighting the associated dysbiosis. Furthermore, Section 3 acknowledged the importance of "strain-dependent" biotherapy to boost beneficial microbiota, modulate immunity, and exert anti-parasitic effects.

The prevalence of sedentary behavior among university students in Saudi Arabia.

BACKGROUND: A considerable body of research has demonstrated that reducing sitting time benefits health. Therefore, the current study aimed to explore the prevalence of sedentary behavior (SB) and its patterns. METHODS: A total of 6975 university students (49.1% female) were chosen randomly to participate in a face-to-face interview. The original English version of the sedentary behavior questionnaire (SBQ) was previously translated into Arabic. Then, the validated Arabic version of the SBQ was used to assess SB. The Arabic SBQ included 9 types of SB (watching television, playing computer/video games, sitting while listening to music, sitting and talking on the phone, doing paperwork or office work, sitting and reading, playing a musical instrument, doing arts and crafts, and sitting and driving/riding in a car, bus or train) on weekdays and weekends. RESULTS: SBQ indicated that the total time of SB was considerably high (478.75 ± 256.60 and 535.86 ± 316.53 (min/day) during weekdays and weekends, respectively). On average, participants spent the most time during the day doing office/paperwork (item number 4) during weekdays (112.47 ± 111.11 min/day) and weekends (122.05 ± 113.49 min/day), followed by sitting time in transportation (item number 9) during weekdays (78.95 ± 83.25 min/day) and weekends (92.84 ± 100.19 min/day). The average total sitting time of the SBQ was 495.09 ± 247.38 (min/day) and 58.4% of the participants reported a high amount of sitting time (≥ 7 hours/day). Independent t-test showed significant differences (P ≤ 0.05) between males and females in all types of SB except with doing office/paperwork (item number 4). The results also showed that male students have a longer daily sitting time (521.73 ± 236.53 min/day) than females (467.38 ± 255.28 min/day). Finally, 64.1% of the males reported a high amount of sitting time (≥ 7 hours/day) compared to females (52.3%). CONCLUSION: In conclusion, the total mean length of SB in minutes per day for male and female university students was considerably high. About 58% of the population appeared to spend ≥7 h/day sedentary. Male university students are likelier to sit longer than female students. Our findings also indicated that SB and physical activity interventions are needed to raise awareness of the importance of adopting an active lifestyle and reducing sitting time.

Evaluating the hepatotoxic versus the nephrotoxic role of iron oxide nanoparticles: One step forward into the dose-dependent oxidative effects.

The present study has been designed to detect the dose-dependent effect of iron oxide nanoparticles (IONPs) on the liver and kidney of rats by evaluating three different doses 30, 300, 1000 mg/kg/day IONPs for 28 days. Forty rats were divided into four groups; I (control), II (low dose), III (medium dose) and IV (high dose). There also was a statistically-significant elevation in the serum levels of hepatic enzymes; AST and ALT in medium & high dose. The elevation of serum ALP, on the other hand, was significant in all IONPs doses. There was significant elevation in the levels of urea creatinine, and MDA in the medium and high doses of IONPs. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed significant decrease in the high dose only compared to the control group. The serum iron levels increased in a dose-dependent manner in the IONPs-treated groups with highly significant increase in the moderate and high dose groups. On comparing the effect of different doses of IONPs between the liver and kidney, the high dose revealed statistically significant difference (p < 0.05) in the area percent of collagen deposition (54.4 ± 3.9 versus 6.1 ± 2.6) and alpha smooth muscle actin (α-SMA) reaction (7.7 ± 1.5 versus 17.8 ± 4.3) in the liver relative to the kidney. The medium and high doses revealed statistically significant difference in optical density of Periodic acid Schiff (PAS) reaction (45 ± 3.4 versus 50.3 ± 1.8 in the medium dose, and 38.9 ± 6 versus 63 ± 3 in the high dose) and area percent of inducible nitric oxide synthase (iNOS) reaction (12.98 ± 2.7 versus 3.5 ± 0.5 in the medium dose, and 27.91 ± 1.5 versus 7.7 ± 0.6 in the high dose) in the liver relative to the kidney.

The synthetic cannabinoid 5F-MDMB-PICA enhances the metabolic activity and angiogenesis in human brain microvascular endothelial cells by upregulation of VEGF, ANG-1, and ANG-2.

Brain angiogenesis, the formation of new blood vessels from existing brain vasculature, has been previously associated with neural plasticity and addictive behaviors related to substances. Synthetic cannabinoids (SCs) have become increasingly popular due to their ability to mimic the effects of cannabis, offering high potency and easy accessibility. In the current study, we reveal that the SC 5F-MDMB-PICA, the most common SC in the United States in 2019, increases cell metabolic activity and promotes angiogenesis in human brain microvascular endothelial cells (HBMECs). First, we performed an MTT assay to evaluate the effects of 5F-MDMB-PICA treatment at various concentrations (0.0001 µM, 0.001 µM, 0.01 µM, 0.1 µM, and 1 µM) on HBMECs metabolic activity. The results demonstrated higher concentrations of the SC improved cell metabolic activity. Furthermore, 5F-MDMB-PICA treatment enhanced tube formation and migration of HBMECs in a dosage-dependent manner. Additionally, the mRNA, secreted protein, and intracellular protein levels of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2, which are involved in the regulation of angiogenesis, as well as the protein levels of cannabinoid receptor type-1, were all increased following treatment with 5F-MDMB-PICA. Notably, the phosphorylation levels at Serine 9 residue of glycogen synthase kinase-3ß were also increased in the 5F-MDMB-PICA treated HBMECs. Collectively, our findings demonstrate that 5F-MDMB-PICA can enhance angiogenesis in HBMECs, suggesting the significant role of angiogenesis in the response to SCs. Manipulating this interaction may pave the way for innovative treatments targeting SC addiction and angiogenesis-related conditions.

Evaluating the protective role of trimetazidine versus nano-trimetazidine in amelioration of bilateral renal ischemia/reperfusion induced neuro-degeneration: Implications of ERK1/2, JNK and Galectin-3 /NF-κB/TNF-α/HMGB-1 signaling.

BACKGROUND: Renal ischemia/reperfusion (I/R) is a primary culprit of acute kidney injury. Neurodegeneration can result from I/R, but the mechanisms are still challenging. We studied the implications of bilateral renal I/R on brain and potential involvement of the oxidative stress (OS) driven extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase (ERK1/2, JNK) and Galectin-3 (Gal-3)/nuclear factor Kappa B (NF-қB)/tumor necrosis factor-alpha (TNF-α), high mobility group box-1 (HMGB-1), and caspase-3 paths upregulation. We tested the impact of Nano-trimetazidine (Nano-TMZ) on these pathways being a target of its neuroprotective effects. METHODS: Study groups; Sham, I/R, TMZ+I/R, and Nano-TMZ+I/R. Kidney functions, cognition, hippocampal OS markers, Gal-3, NF-қB, p65 and HMGB-1 gene expression, TNF-α level, t-JNK/p-JNK and t-ERK/p-ERK proteins, caspase-3, glial fibrillary acidic protein (GFAP) and ionized calcium binding protein-1 (Iba-1) were assessed. RESULTS: Nano-TMZ averted renal I/R-induced hippocampal impairment by virtue of its anti: oxidative, inflammatory, and apoptotic properties. CONCLUSION: Nano-TMZ is more than anti-ischemic.

Assessment of the Impact of Lower Urinary Tract Dysfunction on Quality of Life in Multiple Sclerosis Patients in Saudi Arabia-A Cross-Sectional Study.

BACKGROUND: Lower urinary tract dysfunction (LUTD) is caused by neurogenic factors that could lead to permanent injury in affected patients, and therefore result in substantial annual healthcare expenses. LUTD is very prevalent in multiple sclerosis (MS) patients and has a drastic impact on their quality of life (QOL). This study aimed to assess the effect of LUTD on the QOL of Saudi MS patients. METHODS: A cross-sectional study was carried out in Saudi Arabia using a self-administered questionnaire that included the World Health Organization Quality of Life (WHOQOL-BREF) and LURN Symptom Index (LURN SI-29). Data were analyzed and presented as frequencies and percentages. RESULTS: There were 428 patients who participated in this study; 270 were females and 158 were males. Most of the patients received a low score in all sections of the LURN part of the questionnaire. The highest scores (urgent need to urinate and excessive urination at night) were recorded in the urgency domain (47.20 ± 36.88) rather than the nocturia domain (44.74 ± 32.91). Meanwhile, the lowest score (complete control of bladder) was recorded in the incontinence domain (22.80 ± 26.80). For the WHOQOL-BREF score, the highest score (more social stability) was in the social domain (65.07 ± 21.16 for females, 60.41 ± 21.54 for males), and the lowest score (less psychological stability) was in the psychological domain (46.36 ± 9.84 for females, 46.20 ± 10.03 for males). However, there was no significant association between the four domains of the WHOQOL-BREF and the gender of the MS patients. CONCLUSIONS: LUTD is significantly associated with a lowered quality of life. Therefore, patients are recommended to consult with and be evaluated by appropriately experienced healthcare providers and clinicians. This ensures that the patients receive the best advice, accurate and effective treatment, and long-term analysis that can lead to an improvement in their quality of life.

An Anatomical Study of Dry Mandibles to Determine the Important Surgical Reference Points in Ramus Osteotomy - An Evaluative Study.

Introduction: The variable relation and clinical significance of mandibular foramen (MF) and Lingula with inferior alveolar neurovascular bundle (IANB) is important for dental surgeons. Knowing the landmarks on the ramus of the mandible is of paramount importance to perform the surgery without causing damage to the neurovascular bundle. Materials and Methods: This study was conducted on 85 dry adult mandibles of unknown sex and age. The distances were measured from the anatomical reference points (anti-Lingula, Lingula and MF) using digital callipers. Results: The distance from the anti-Lingula to the anterior border of the ramus (A) was significantly longer on the right side (14.91 mm) than on the left side (14.5 mm). There was a significant difference in mean distances between the anti-Lingula and MF of both the sides (P ≤ 0.005). No significant difference was noted in the distances between the Lingula and the Anti-Lingula, observed for the posterior (B, P = 0.75) and the inferior margin of the mandible (D, P = 0.54). However we found correlation of vertical distances of anti-Lingula with Lingula and MF exhibited moderate positive correlation. Discussion: The IANB is prone to damage during mandibular surgery. Using anti-Lingula alone as a reference point is not guaranteed, but it is still an important anatomical landmark for the surgeon to operate.

The Patients' Perspective for the Impact of Late Detection of Ocular Diseases on Quality of Life: A Cross-Sectional Study.

Background: Late detection of ocular diseases negatively affects patients' quality of life (QoL), encompassing health status, psychological, financial, and social aspects. However, the early detection of eye conditions leads to rapid intervention and avoiding complications, thus preserving the QoL. This study assessed the impact of ocular diseases late detection on patients' QoL at multi-eye clinics based on questionnaire responses. Methods: We developed an original Arabic-English questionnaire to assess the QoL of patients with ocular diseases referred from primary and secondary healthcare centers to tertiary hospitals. It covered preliminary data, patient perspectives on having lately detected ocular disease and treatment costs, and the impact of late detection on finances, social life, psychology, health status, and awareness of current initiatives. Logistic regression analysis was used to explore the associations between patient perspectives on having ocular diseases detected at a late stage and its impact on different domains. Multivariate logistic regression was applied with impact types of health status, psychological, financial, and social (dependent variables) and age, income levels, and hospital type (independent variables). Results: Three hundred and eighty-eight responded, with 50% experiencing psychological effects, 27% health issues, 23% social impacts, and 23% financial burdens. Two hundred seventeen patients (56%) reported having ocular condition detected in late stage. Logistic regression analysis showed positive association with health status, social well-being, and financial effects (p < 0.05). Multivariate analysis revealed pronounced effects in patients ≤ 50 years, with income \< 5000 SAR, and those visiting private clinics (p < 0.05). The social impact was greater in patients visiting private hospitals. Ninety percent of all patients emphasized the importance of increasing awareness for better QoL. Conclusion: Significant associations were found between the late detection of eye diseases and their impact on QoL. Therefore, early detection and increasing patients' awareness of ocular diseases and treatment are essential.

Nuclear factor erythrogen-2 associated factor 2 (Nrf2) signaling is an essential molecular pathway for the anti-aging effect of whey protein in the prefrontal cortex of aging rat model (Histological and Biochemical Study).

Aging is a highly complicated natural process. Brain aging is associated with remarkable neurodegenerative changes and oxidative damage. Whey protein (WP) has been mentioned to have an antioxidant property. Nuclear factor erythrogen-2 associated factor 2 (Nrf2) signaling pathway is an antioxidant defense system. Nrf2 activity declines with age so, its activation could be a promising therapeutic strategy for aging. This study aimed to explore the anti-aging role of WP against D-galactose (D-gal) induced age-related degenerative changes and oxidative damage in the prefrontal cortex (PFC) and investigate its underlying mechanisms. Forty adult male rats were divided into 4 groups; control, WP group received WP (28.77 mg/kg/day) by gastric tube on the 4th experimental week; D-gal (model group) received D-gal (300 mg/kg/day) intraperitoneally for 8 weeks and D-gal +WP group received WP on the 4th week of D-gal treatment. Specimens from PFC were obtained for biochemical, histological, immunohistochemical and western blot analysis. WP treatment in D-gal +WP group reduced lipid peroxidation, enhanced antioxidant enzyme activities, decreased advanced glycation end products level and improved the histological and ultrastructural alterations. Moreover, the number of neurons expressed the senescence marker; p21 and percentage area of the astrocytic marker; glial fibrillary acidic protein were significantly reduced. WP also enhanced Nrf2 pathway and its downstream targets; heme oxygenase-1 and NADPH quinone oxidoreductase 1. In conclusion WP alleviates the D-gal-induced PFC aging through activating Nrf2 pathway, reducing cell senescence and gliosis. So, it may be a potential therapeutic target to retard the aging process.