The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of circYAP1/miRNA-21/TLR7 Axis.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 (circYAP1) and microRNA-21 (miRNA-21) in the rat knee joints. METHODOLOGY: Gene expression circYAP1, miRNA-21, toll-like receptor-7 (TLR7), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. RESULTS: Our results showed that BM-MSCs-derived exosomes significantly elevated circYAP1 gene expression level (p < 0.05) along with subsequent downregulation of miRNA-21 and TLR7 (p < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction (p < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers (p < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups (p < 0.05). CONCLUSION: Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.

Investigating CHRNA5, CHRNA3, and CHRNB4 variants in the genetic landscape of substance use disorder in Jordan.

BACKGROUND: Substance use disorder (SUD) is a complex illness that can be attributed to the interaction between environmental and genetic factors. The nicotinic receptor gene cluster on chromosome 15 has a plausible association with SUD, particularly with nicotine dependence. METHODS: This study investigated 15 SNPs within the CHRNA5, CHRNA3, and CHRNB4 genes. Sequencing was used for genotyping 495 Jordanian males with SUD and 497 controls matched for age, gender, and descent. RESULTS: Our findings revealed that none of the tested alleles or genotypes were correlated with SUD. However, our analysis suggests that the route of substance use was linked to rs1051730 (P value = 0.04), rs8040868 (P value = 0.01) of CHRNA3, and rs16969968 (P value = 0.03) of CHRNA5. Additionally, a correlation was identified between rs3813567 of the CHRNB4 gene and the age at substance use onset (P value = 0.04). CONCLUSIONS: Variants in CHRNA5, CHRNA3, and CHRNB4 may interact with SUD features that can influence the development and progression of the disorder among Jordanians.

Polycyclic aromatic hydrocarbons in indoor mosques dust in Saudi Arabia: Levels, source apportionment, human health and carcinogenic risk assessment for congregators.

Mosques are important places for Muslims where they perform their prayers. The congregators are exposed to hazardous pollutants such as polycyclic aromatic hydrocarbons (PAHs) associated with dust. However, studies on PAHs exposure in religious places are scarce. Air-condition filter (ACF) dust can correspond to air quality to a certain extent, since dust particles derived from indoor and outdoor places stick to it. Therefore, the present study aimed to evaluate the 16 EPA PAHs in ACF dust from mosques to determine their levels, profiles, sources and risks. Average Σ16 PAHs concentrations were 1039, 1527, 2284 and 5208 ng/g in AC filter dust from mosques in residential (RM), suburban (SM), urban (UM) and car repair workshop (CRWM), respectively, and the differences were statistically significant (p < 0.001). Based on the molecular diagnostic PAH ratios, PAHs in mosques dust is emitted from local incomplete fuel combustion, as well as complete fossil fuels combustion sources (pyrogenic), petroleum spills, crude and fuel oil, traffic emissions, and other possible sources of industrial emissions in different functional areas. The incremental lifetime cancer risks (ILCRs) values for children and adults across the different types of mosques follow the order: CRWM > UM > SM > RM. ILCRs values for both children and adults were found in order: dermal contact > ingestion > inhalation. The cancer risk levels via ingestion for children were relatively higher than the adults. The values of cancer risk for children and adults via dermal contact and ingestion (except in RM) were categorized in the 'potentially high risk' category (> 10-4). The mean values of total cancer risks (CR) for children (5.74 × 10-3) and adults (5.07 × 10-3) in mosques also exceeded the accepted threat value (>10-4). Finally, it is recommended that regular and frequent monitoring of PAHs should be carried out in mosques to improve the quality and maintain the health of congregators around the globe.

Effect of Selenium nanoparticles on Paraquat-induced-neuroinflammation and oligodendocyte modulation: Implication of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.

BACKGROUND: Paraquat (PQ), is an extensively used herbicide and is a well-established powerful neurotoxin. However, the mechanism underlying its neurotoxicity still needs further investigation. AIM OF WORK: The study investigated the pathogenesis of PQ-induced neuroinflammation of the substantia nigra pars compacta (SNPC) and cerebellum and evaluated the potential effect of selenium nanoparticles (SeN) against such neurotoxicity. METHODS: Thirty-six mice were randomly divided into three groups; Control group, PQ group: mice received PQ 10 mg/kg (i.p), and PQ + SeN group; mice received PQ in addition to oral SeN 0.1 mg/kg. All regimens were administered for 14 days. The mice's brains were processed for biochemical, molecular, histological, and immune-histochemical assessment. RESULTS: SeN increased the SNPC and cerebellum antioxidants (reduced glutathione, glutathione peroxidase, and superoxide dismutase 1) while decreasing malondialdehyde concentration. Also, SeN increased the anti-inflammatory interleukin (IL)-10 and decreased the pro-inflammatory IL-1ß and -6 along with improving the angiogenic nitric oxide and reducing caspase-1. Further, western blots of phosphorylated Janus kinase (JAK2)/signal transducer and activator of transcription3 (STAT3) proteins showed a significant decline. Those improving effects of SeN on SNPC, and cerebellum were supported by the significantly preserved dopaminergic and Purkinje neurons, the enhanced myelin fibers on Luxol fast blue staining, and the marked increase in Olig-2, Platelet-derived growth factor-alpha, and tyrosine hydroxylase immunoreactivity. CONCLUSION: SeN could mitigate PQ-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic properties.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.