Deciphering the intrinsically disordered characteristics of the FG-Nups through the lens of polymer physics.

The nuclear pore complex (NPC) is a critical gateway regulating molecular transport between the nucleus and cytoplasm. It allows small molecules to pass freely, while larger molecules require nuclear transport receptors to traverse the barrier. This selective permeability is maintained by phenylalanine-glycine-rich nucleoporins (FG-Nups), intrinsically disordered proteins that fill the NPC's central channel. The disordered and flexible nature of FG-Nups complicates their spatial characterization with conventional structural biology techniques. To address this challenge, polymer physics offers a valuable framework for describing FG-Nup behavior, reducing their complex structures to a few key parameters. In this review, we explore how polymer physics models FG-Nups using these parameters and discuss experimental efforts to quantify them in various contexts, providing insights into the conformational properties of FG-Nups.

A practical approach to demonstrate the circular economy in remediation of textile dyes using nutraceutical industrial spent.

We used Nutraceutical Industrial Coriander Seed Spent (NICSS), a readily available, cheap, eco-friendly, and ready-to-use material, as an innovative adsorbent for the bioremediation of a bisazo Acid Red 119 (AR 119) dye, which is likely a mutagen from textile industrial effluents (TIE). A laboratory-scale experiment was tailored to demonstrate the framework of the circular economy (CE) in the remediation of textile dyes using Nutraceutical Industrial Spent to align with the principles of sustainability and valorization. An experimental q e value of 97.00 mg g-1 was obtained. For the practicality and effectiveness of the method, a two-level fractional factorial experimental design (FFED) was employed to determine variables that influence the adsorption capacity of NICSS. At optimal settings (pH of 1.4, adsorbent dosage of 6.000 g L-1, adsorbent particle size of 96 µm, initial dye concentration of 599 mg L-1, adsorption duration of 173 min, orbital shaking speed of 165 rpm, and temperature of 35 °C), the maximum adsorption efficiency achieved through statistical optimization was 614 mg g-1. Six factors influencing the adsorption process were examined experimentally and were considered important for commercialization. Three orders of magnitude were applied to the identified variables in scaling experiments. Adsorption-equilibrium data were analyzed using nine isotherm models. The best fit was discovered to be the Vieth-Sladek adsorption isotherm model. The suitable mechanism for the overall rate of the adsorption process was a pseudo-second-order reaction: mass-transfer mechanistic studies were predicted to predominate over the diffusion process. NICSS was characterized using SEM and FTIR spectroscopy. Utilizing plastic trash, the dye-adsorbed NICSS that was recovered as "sludge" was utilized as a reinforcing material to create composites. Dye-adsorbed NICSS thermoplastic and thermoset composites were studied and compared with NICSS composites in terms of their physicomechanical and chemical properties.

Cancer Patients Satisfaction and Quality of Healthcare Services in Iraq: A Cross-Sectional Study to Evaluate the Quality of Care in Cancer Management.

OBJECTIVE: Cancer is a complex disease characterized by uncontrolled cell proliferation and the development of metastatic features. The aim of the study is to examine the patient's satisfaction with the quality of healthcare services provided at the Middle Euphrates Cancer Centre in Al-Najaf Al-Ashraf Governorate. METHODS: Cancer patients who visited during 2021-2023 Middle Euphrates Cancer Center in Al-Najaf Al Ashraf Governorate in 2021-2023 were enrolled in the study. In the cross sectional study, enrolled cancer patients were screened based on inclusion and exclusion criteria. In this study, cancer patient satisfaction assessment was made based on responses from a 59 items questionnaire. RESULTS: In the study period, 400 cancer patients who visited the Middle Euphrates Cancer Center in Al-Najaf Al Ashraf Governorate enrolled in the study. Cancer patient's satisfaction was assessed based on the care provided by physicians, nurses, the infrastructure of the organization, and their socioeconomic status. Under the category of care provided by the physician, the level of assessment reported was low [L] =1-2.33; moderate [M] =2.34-3.66; 2.34-3.66, and high [H] =3.67-5). However, in the case of care provided by nurses, the level of assessment is low ([L] =1-2.33; moderate [M]=2.34-3.66; high [H]=3.67-5.0). The level of assessment (low [L] =1-2.33; moderate [M] = -3.66; high [H]=3.67-5) at the organization level for the services and facilities. CONCLUSION: Findings clearly demonstrate that the participants were dissatisfied with some services provided by doctors, nurses, or organizations. The findings also emphasize the critical need to tailor healthcare services, enhance accessibility, and elevate the overall quality of care to enhance patient satisfaction significantly.

Evaluating a Modified Use of the Kaiser Permanente Early-onset Sepsis Risk Calculator to Reduce Antibiotic Exposure: a Retrospective Study.

BACKGROUND: Early-onset neonatal sepsis (EONS) remains an important disease entity due to very serious adverse outcomes if left untreated. Lack of diagnostic tools in identifying healthy from diseased neonates, and clinicians' fear of the missing positive-culture sepsis babies, or babies with clinical sepsis have led to overtreating and unnecessary antibiotic exposure. Kaiser Permanente EONS risk calculator is an internally validated tool that can predict EONS. This sepsis risk calculator (SRC) classifies neonates into three subgroups: (1) ill-appearing, (2) equivocal and (3) well-appearing. We propose a modification to this tool that aims to use it solely for well-appearing babies. This modification represents a more conservative approach to decrease antibiotic exposure and offers an alternative for those hesitant to fully implement this tool. METHODS: This is a dual-centre retrospective study where data were extracted from the electronic medical records. Our primary outcome was to validate the modified use of the SRC with a two-by-two table. Specificity, negative predictive value and expected antibiotic reduction were used to evaluate the tool's feasibility. RESULT: Among 770 babies suspected of EONS, the feasibility of the modified use was tested. The expected antibiotic exposure reduction rate on the modification was 40.4% overall. The proposed modification resulted in a specificity and negative predictive value of 99.28% (95% CI: 97.92% to 99.85%) and 99.5% (95% CI: 99% to 99.8%), respectively. CONCLUSION: The modified use of the sepsis risk calculator has shown that it can safely reduce antibiotic exposure in well-appearing babies. The modified use is used as a 'rule out' test that can identify very low risk of EONS babies, and safely minimise antibiotic exposure. Further prospective studies are needed to examine the efficacy of this use, and quality improvement projects are required to evaluate its applicability in different clinical settings.

Physiotherapists' awareness and use of red flags for the assessment of low back pain in Saudi Arabia.

BACKGROUND: Physiotherapists must identify potential red flags that may impede recovery and function in individuals with low back pain (LBP) or put them at risk. OBJECTIVES: This study aimed to (1) investigate physiotherapists' awareness and use of red flags for individuals with LBP in Saudi Arabia and (2) identify factors associated with their awareness and use of LBP red flags. METHODS: This cross-sectional study collected data using an anonymous online questionnaire (February-July 2023). It included physiotherapists working in private/public hospitals in Saudi Arabia. The questionnaire asked about the participants' characteristics, their awareness of LBP red flags, and their use of red flags for LBP assessment. RESULTS: A total of 643 participating physiotherapists (26.2 ± 3.8 years), 63.8% of whom were females, completed the survey. Most participants (94.4%) had adequate awareness of LBP red flags, and more than half (61%) had good utilization of red flags when assessing individuals with LBP. There was a positive correlation between the physiotherapists' awareness and use of LBP red flags. CONCLUSION: The majority of the participating physiotherapists in Saudi Arabia were aware of LBP red flags, and many reported to have good use of red flags in clinical practice when assessing and managing individuals with LBP.

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.

Poor lumbar spine coordination in acute low back pain predicts persistent long-term pain and disability.

PURPOSE: Sitting balance on an unstable surface requires coordinated out-of-phase lumbar spine and provides sufficient challenge to expose quality of spine control. We investigated whether the quality of spine coordination to maintain balance in acute low back pain (LBP) predicts recovery at 6 months. METHODS: Participants in an acute LBP episode (n = 94) underwent assessment of sitting balance on an unstable surface. Seat, hip and spine (lower lumbar, lumbar, upper lumbar, thoracic) angular motion and force plate data were recorded. Coordination between the seat and hip/spine segments to maintain balance was quantified in the frequency domain to evaluate coordination (coherence) and relative timing (phase angle: in-phase [segments move together]; out-of-phase [segments move opposite]). Center of pressure (CoP) and upper thorax motion assessed overall balance performance. Hip and spine coordination with the seat were compared between those who did not recover (increased/unchanged pain/disability), partially recovered (reduced pain/disability) or recovered (no pain and disability) at 6 months. RESULTS: In both planes, coherence between the seat and lower lumbar spine was lower (and in-phase-unhelpful for balance) at baseline in those who did not recover than those who recovered. Coherence between the seat and hip was higher in partially recovered in both planes, suggesting compensation by the hip. LBP groups had equal overall balance performance (CoP, upper thorax motion), but non-recovery groups used a less optimal strategy that might have consequences for long-term spine health. CONCLUSION: These longitudinal data revealed that individuals with compromised contribution of the lumbar spine to the balance during unstable sitting during acute LBP are less likely to recover.

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.

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.

Trunk postural control during unstable sitting among individuals with and without low back pain: A systematic review with an individual participant data meta-analysis.

INTRODUCTION: Sitting on an unstable surface is a common paradigm to investigate trunk postural control among individuals with low back pain (LBP), by minimizing the influence lower extremities on balance control. Outcomes of many small studies are inconsistent (e.g., some find differences between groups while others do not), potentially due to confounding factors such as age, sex, body mass index [BMI], or clinical presentations. We conducted a systematic review with an individual participant data (IPD) meta-analysis to investigate whether trunk postural control differs between those with and without LBP, and whether the difference between groups is impacted by vision and potential confounding factors. METHODS: We completed this review according to PRISMA-IPD guidelines. The literature was screened (up to 7th September 2023) from five electronic databases: MEDLINE, CINAHL, Embase, Scopus, and Web of Science Core Collection. Outcome measures were extracted that describe unstable seat movements, specifically centre of pressure or seat angle. Our main analyses included: 1) a two-stage IPD meta-analysis to assess the difference between groups and their interaction with age, sex, BMI, and vision on trunk postural control; 2) and a two-stage IPD meta-regression to determine the effects of LBP clinical features (pain intensity, disability, pain catastrophizing, and fear-avoidance beliefs) on trunk postural control. RESULTS: Forty studies (1,821 participants) were included for the descriptive analysis and 24 studies (1,050 participants) were included for the IPD analysis. IPD meta-analyses revealed three main findings: (a) trunk postural control was worse (higher root mean square displacement [RMSdispl], range, and long-term diffusion; lower mean power frequency) among individuals with than without LBP; (b) trunk postural control deteriorated more (higher RMSdispl, short- and long-term diffusion) among individuals with than without LBP when vision was removed; and (c) older age and higher BMI had greater adverse impacts on trunk postural control (higher short-term diffusion; longer time and distance coordinates of the critical point) among individuals with than without LBP. IPD meta-regressions indicated no associations between the limited LBP clinical features that could be considered and trunk postural control. CONCLUSION: Trunk postural control appears to be inferior among individuals with LBP, which was indicated by increased seat movements and some evidence of trunk stiffening. These findings are likely explained by delayed or less accurate corrective responses. SYSTEMATIC REVIEW REGISTRATION: This review has been registered in PROSPERO (registration number: CRD42021124658).

Coordination of hip and spine in individuals with acute low back pain during unstable sitting.

BACKGROUND CONTEXT: Trunk postural control differs between individuals with and without chronic low back pain (LBP). Whether this corresponds to differences in hip/spine coordination during the early acute phase of LBP (ALBP) is unclear. PURPOSE: To compare hip/spine coordination in relation to seat movements between individuals with and without ALBP when balancing on an unstable seat and to identify coordination strategies to maintain balance using cluster analysis. STUDY DESIGN/SETTING: Cross-sectional observational study. PATIENT SAMPLE: ALBP (n=130) and pain-free (n=72) individuals. OUTCOME MEASURES: Frequency domain measures to evaluate hip/spine coordination (amplitude spectrum, phase angle, and coherence) and time-series measures to assess overall balance performance (center of pressure [CoP] reflecting the amount of seat movements, upper thorax motion as a surrogate for head motion). METHODS: Participants maintained balance while sitting on a seat fixed to a hemisphere. Seat, hip, and spine (lower lumbar, lumbar, upper lumbar, and thoracic) angular motion and force plate data were recorded. RESULTS: Overall, seat/CoP movements (amplitude spectrum and RMSdisplacement) were greater (in both planes) and sagittal coordination (coherence) between the hip or lower spine and seat movements was lower in ALBP than controls. Cluster analysis using coherence data revealed different coordination strategies to maintain balance. Separate clusters used a "lower lumbar strategy" and "hip strategy" in the sagittal plane, and a "lower and upper lumbar strategy" and "lower lumbar strategy" in the frontal plane. A cluster using a "low coherence strategy" in both planes was also identified. CONCLUSIONS: Hip and lower spine coordination was less in individuals with ALBP in conjunction with a lower quality of overall balance performance. However, interpretation of the relationship between coherence and overall balance performance was not straightforward. Clusters in both the ALBP group and the control group adopted a low coherence strategy, and this was not consistently related to poor overall balance performance. This suggests overall balance performance cannot be inferred from coherence alone and requires consideration of interaction of other different features.

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.

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.

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.

Suppression of neuronal apoptosis and glial activation with modulation of Nrf2/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy.

Introduction: Diabetes is a global disease, commonly complicated by neuropathy. The spinal cord reacts to diabetes by neuronal apoptosis, microglial activation, and astrocytosis, with a disturbance in neuronal and glial Nuclear factor erythroid 2-related factor/Heme oxygenase-1 (Nrf2/HO-1) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling. Curcumin, a bioactive natural substance, showed neuroprotective role in many diseases. However, its role in the treatment of the diabetic central neuropathy of spinal cord and the underlying mechanisms still need clarification. The present study tried to evaluate the role of curcumin in diabetes-induced central neuropathy of the spinal cord in rats. Methods: Twenty rats were divided into three groups; group 1: a negative control group; group 2: received streptozotocin (STZ) to induce type I diabetes, and group 3: received STZ + Curcumin (150 mg/kg/day) for eight weeks. The spinal cords were examined for histopathological changes, and immunohistochemical staining for Glia fibrillary acidic protein (GFAP); an astrocyte marker, Ionized calcium-binding adaptor molecule 1 (Iba1), a microglial marker, neuronal nuclear protein (NeuN); a neuronal marker, caspase-3; an apoptosis marker, Nrf2/HO-1, NF-kB, and oxidative stress markers were assessed. Results: Curcumin could improve spinal cord changes, suppress the expression of Iba1, GFAP, caspase-3, and NF-kB, and could increase the expression of NeuN and restore the Nrf2/HO-1 signaling. Discussion: Curcumin could suppress diabetic spinal cord central neuropathy, glial activation, and neuronal apoptosis with the regulation of Nrf2/HO-1 and NF-kB signaling.

Phosphodiesterase1 inhibitor "Vinpocetine" ameliorates the inflammation, apoptosis and oxidative stress induced by cyclophosphamide in urinary bladder: an experimental study.

BACKGROUND: Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CP). Vincamine (vinca alkaloid) is the source of the synthetic derivative vinpocetine (Vinpo). Worldwide, Vinpo is used as a cerebroprotective drug. As it has anti-oxidant, anti-thrombotic and anti-inflammatory effects but the power of Vinpo to prevent CP induced cystitis has not been studied. AIM OF STUDY: This research was planned to explore the effect of Vinpo (10-30 mg/kg, orally) administered 1 or 4 h before inducing cystitis by CP injection (300 mg/kg, i.p.) on the urinary bladder of mice. RESULTS: Administration of Vinpo 30 mg/kg, 4 h before CP injection ameliorated inflammatory markers. It reduced inducible nitric oxide synthase (iNOS), tumor necrosis factor- α (TNF-α), and BCL2 Associated X (Bax) expression in the bladder and increased the total antioxidant capacity level. Histological examination of the bladder has further supported these results. The present study suggests a protective effect of Vinpo (30 mg/kg, 4 h before CP injection) against CP-induced bladder inflammation. CONCLUSION: This proposes that Vinpo 30 mg/kg may become a promising pharmacological drug to prevent urinary adverse effects in patients treated with chemotherapy using CP.

Neuroprotective effect of ranolazine improves behavioral discrepancies in a rat model of scopolamine-induced dementia.

Background: Ranolazine (Rn), an antianginal agent, acts in the central nervous system and has been used as a potential treatment agent for pain and epileptic disorders. Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases and the leading factor in dementia in the elderly. Aim: We examined the impact of Rn on scopolamine (Sco)-induced dementia in rats. Methods: Thirty-two albino male rats were divided into four groups: control, Rn, Sco, and Rn + Sco. Results: A significant decrease in the escape latency in the Morris water maze test after pre-treatment with Rn explained better learning and memory in rats. Additionally, Rn significantly upregulated the activities of the antioxidant enzymes in the treated group compared to the Sco group but substantially reduced acetylcholinesterase activity levels in the hippocampus. Moreover, Rn dramatically reduced interleukin-1 ß (IL-1ß) and IL-6 and upregulated the gene expression of brain-derived neurotrophic factor (BDNF). Furthermore, in the Sco group, the hippocampal tissue's immunohistochemical reaction of Tau and glial factor activating protein (GFAP) was significantly increased in addition to the upregulation of the Caspase-3 gene expression, which was markedly improved by pre-treatment with Rn. The majority of pyramidal neurons had large vesicular nuclei with prominent nucleoli and appeared to be more or less normal, reflecting the all-beneficial effects of Rn when the hippocampal tissue was examined under a microscope. Conclusion: Our findings indicated that Rn, through its antioxidative, anti-inflammatory, and anti-apoptotic effects, as well as the control of the expression of GFAP, BDNF, and Tau proteins, has a novel neuroprotective impact against scopolamine-induced dementia in rats.

Potential role for vitamin D vs. intermittent fasting in controlling aquaporin-1 and aquaporin-3 expression in HFD-induced urinary bladder alterations in rats.

Background: High-fat diet-induced obesity is linked to suppression of aquaporins (AQPs) expression in different tissues. Both vitamin D and intermittent fasting were identified to enhance AQPs expression. In the urinary bladder, AQP-1 and AQP-3 mRNA transcripts were identified. Vitamin D has an impact on a variety of genes that encode proteins that control cell proliferation, differentiation, and death. Aim: To assess potential benefits of vitamin D and intermittent fasting (IF) and to explore alterations to the urinary bladder triggered by high-fat diet (HFD) in a rat model of obesity. Methods: Each of the 4 groups contained six adult male albino rats; control: a standard rodent chew for 12 weeks, HFD: HFD and fructose were administered orally via gastric gavage for 12 weeks, and vitamin D: HFD and fructose were administered orally for 8 weeks, then 4 weeks of intraperitoneal injection of vitamin D (5 microns/Kg/2 days) and IF group: Received intraperitoneal injections of vitamin D (5 microns/Kg/2 days) for 4 weeks after consumption of HFD and fructose orally for 8 weeks. The serum lipid profile was conducted at end of the experiment. In the bladder homogenates, the levels of oxidative stress indicators were assessed. Quantitative real-time PCR was performed on recently collected bladder samples. AQP-1 and AQP-3 immunohistochemistry was done. Results: When compared to the HFD group, the vitamin D and IF groups both demonstrated a substantial improvement in histopathological, immunohistochemical, biochemical, and molecular markers. Conclusion: In all examined parameters, IF exceeded vitamin D as a preventive factor for the urinary bladder deterioration.

Neuroprotective effect of naringin against cerebellar changes in Alzheimer's disease through modulation of autophagy, oxidative stress and tau expression: An experimental study.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual cognitive decline. Strong antioxidants that inhibit free radicals, such as polyphenols, reduce the likelihood of developing oxidative stress-related degenerative diseases such as AD. Naringin, a flavonoid found in citrus fruit shown to be neuroprotective, reduce oxidative damage and minimize histopathological changes caused by ischemic reperfusion, enhance the long-term memory in AD animal models. This work aimed to comprehend the role of naringin in the defense of the cerebellum against aluminum chloride (AlCl3)-induced AD in rats by investigating the behavioral, neurochemical, immunohistochemical, and molecular mechanisms that underpin its possible neuroprotective effects. Twenty-four adult albino rats were divided into four groups (n = 6/group): (i) Control (C) received saline per oral (p.o.), (ii) Naringin(N)-received naringin (100 mg/kg/d) p.o, (iii) AlCl3-recived AlCl3 (100 mg/kg/d) p.o and (iv) AlCl3 + Naringin (AlCl3 + N) received both AlCl3 and naringin p.o for 21 days. Behavioral tests showed an increase in the time to reach the platform in Morris water maze, indicating memory impairment in the AlCl3-treated group, but co-administration of naringin showed significant improvement. The Rotarod test demonstrated a decrease in muscle coordination in the AlCl3-treated group, while it was improved in the AlCl3 + N group. Neurochemical analysis of the hippocampus and cerebellum revealed that AlCl3 significantly increased lipid peroxidation and oxidative stress and decreased levels of reduced glutathione. Administration of naringin ameliorated these neurochemical changes via its antioxidant properties. Cerebellar immunohistochemical expression for microtubule assembly (tau protein) and oxidative stress (iNOS) increased in A1C13-treated group. On the other hand, the expression of the autophagic marker (LC3) in the cerebellum showed a marked decline in AlCl3-treated group. Western blot analysis confirmed the cerebellar immunohistochemical findings. Collectively, these findings suggested that naringin could contribute to the combat of oxidative and autophagic stress in the cerebellum of AlCl3-induced AD.

Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson's disease rat model.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Treatment of PD is challenging, as current treatment strategies are only symptomatic and do not stop disease development. Recent studies reported neuroprotective effects of calcitriol in PD through its antioxidant and anti-inflammatory properties. The exact pathomechanisms of PD are not yet fully understood. So, investigation of different molecular pathways is challenging. Sirtuin-1 (Sirt1) modulates multiple physiological processes, including programmed cell death, DNA repair, and inflammation. Furthermore, defective autophagy is considered a key pathomechanism in PD as it eliminates protein aggregation and dysfunctional cell organelles. The present study investigated the involvement of autophagy and Sirt1/NF-κB molecular pathway in rotenone-induced PD and explored the protective and restorative effects of calcitriol through these mechanisms. Therefore, behavioral tests were used to test the effect of calcitriol on motor disability and equilibrium. Furthermore, the histological and neuronal architecture was assessed. The expression of genes encoding neuroinflammation and autophagy markers was determined by qPCR while their protein levels were determined by Western blot analysis and immune-histochemical staining. Our results indicate that behavioral impairments and dopaminergic neuron depletion in the rotenone-induced PD model were improved by calcitriol administration. Furthermore, calcitriol attenuated rotenone-induced neuroinflammation and autophagy dysfunction in PD rats through up-regulation of Sirt1 and LC3 and down-regulation of P62 and NF-κB expression levels. Thus, calcitriol could induce a neuro-protective and restorative effect in the rotenone-induced PD model by modulating autophagy and Sirt1/NF-κB pathway.