Evaluation of the hepatoprotective effect of curcumin-loaded solid lipid nanoparticles against paracetamol overdose toxicity: Role of inducible nitric oxide synthase.

Curcumin (Cur) is a natural compound that exhibited therapeutic effects against various liver injuries however Cur showed poor water solubility and bioavailability. This study aimed to design Cur-loaded solid lipid nanoparticles (SLNs) and to evaluate the hepatoprotective and antioxidant effects in a model of acute hepatotoxicity induced by paracetamol (PCM) overdose compared to the raw Cur and N-acetylcysteine (NAC). SLNs were prepared by emulsion/solvent evaporation method and 32 factorial design was employed. Wistar rats were divided into Control, PCM, PCM + NAC, PCM + raw Cur, and PCM + Cur-SLNs groups and treated orally for 14 days before receiving a single PCM dose. The Cur-loaded SLNs showed high entrapment efficiency % ranging between 69.1 and 92.1%, particle size (PS) between 217 and 506 nm, and zeta potential values between -17.9 and -25.5 mV. The in vivo results revealed that the PCM group exhibited deterioration of liver functions, pathological lesions on the liver tissues, severe oxidative stress, and increases in both the serum and hepatic iNOS levels. Remarkably, the PCM + Cur-SLNs group showed significantly better liver functions and tissue integrity compared to the PCM group. Furthermore, higher reduced glutathione and catalase but lower malondialdehyde and iNOS levels were observed. In conclusion, Cur-loaded SLNs effectively prevented the liver damage induced by PCM overdose through alleviating the oxidative stress and inhibiting the serum and hepatic iNOS expression in an effect comparable to NAC and better than raw Cur.

Betaine downregulates microRNA 34a expression via a p53-dependent manner in cisplatin-induced nephrotoxicity in rats.

Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1ß compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1ß as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

Detecting liver fibrosis using a machine learning-based approach to the quantification of the heart-induced deformation in tagged MR images.

Liver disease causes millions of deaths per year worldwide, and approximately half of these cases are due to cirrhosis, which is an advanced stage of liver fibrosis that can be accompanied by liver failure and portal hypertension. Early detection of liver fibrosis helps in improving its treatment and prevents its progression to cirrhosis. In this work, we present a novel noninvasive method to detect liver fibrosis from tagged MRI images using a machine learning-based approach. Specifically, coronal and sagittal tagged MRI imaging are analyzed separately to capture cardiac-induced deformation of the liver. The liver is manually delineated and a novel image feature, namely, the histogram of the peak strain (HPS) value, is computed from the segmented liver region and is used to classify the liver as being either normal or fibrotic. Classification is achieved using a support vector machine algorithm. The in vivo study included 15 healthy volunteers (10 males; age range 30-45 years) and 22 patients (15 males; age range 25-50 years) with liver fibrosis verified and graded by transient elastography, and 10 patients only had a liver biopsy and were diagnosed with a score of F3-F4. The proposed method demonstrates the usefulness and efficiency of extracting the HPS features from the sagittal slices for patients with moderate fibrosis. Cross-validation of the method showed an accuracy of 83.7% (specificity = 86.6%, sensitivity = 81.8%).

A novel chemoprotective effect of tiopronin against diethylnitrosamine-induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK-P53 signalling cascade.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Oxidative stress contributes significantly to HCC pathogenesis. In this study, we investigated the possible chemoprotective effect of the thiol group-containing compound, tiopronin, against HCC induced chemically by diethylnitrosamine (DENA) in rats. In addition, we elucidated the possible underlying molecular mechanism. Adult male Wistar rats were divided into: Control group, DENA-treated group and tiopronin + DENA-treated group. Liver function tests (ALT, AST, ALP, albumin, total and direct bilirubin) as well as alpha fetoprotein (AFP) concentration were measured in the sera of samples. Oxidative stress biomarkers such as malondialdehyde, nitric oxide, catalase and glutathione peroxidase were measured in the liver tissue homogenates. Determination of the phosphorylated apoptosis signal-regulating kinase 1 (phospho-ASK1), phospho-P38 and phospho-P53 proteins by western blotting, caspase 3 by immunofluorescence in addition to histopathological examination of the liver tissues were performed. Our results showed that tiopronin prevented the DENA-induced elevation of the liver function enzymes and AFP. It also preserved the activities of antioxidant enzymes as well as providing protection from the appearance of HCC histopathological features. Interestingly, tiopronin significantly decreased the expression level of phospho-ASK1, phospho-P38 and phospho-P53, caspase 3 in the liver tissues. These novel findings suggested that tiopronin is an antioxidant drug with a chemoprotective effect against DENA-induced HCC through maintaining the normal activity of ASK1/ P38 MAPK/ P53 signalling pathway.

Diagnosis of Acute Kidney Injury in Children Hospitalized in a Sub-Saharan African Unit by Saliva Urea Nitrogen Dipstick Test.

INTRODUCTION: Acute kidney injury in pediatric patients (pAKI) is common in developing countries and leads to significant morbidity and mortality. Most nephrology services in developing countries are only in larger cities and for that reason many cases remain undiagnosed. We evaluated the performance of a saliva urea nitrogen (SUN) dipstick to diagnose pAKI in Sudan. METHODS: We collected demographic and clinical information, serum creatinine (SCr), blood urea nitrogen (BUN), SUN, and urine output (UO) in children with pAKI. pAKI was diagnosed based on different criteria (Risk, Injury, Failure, Loss of kidney function, and end-stage kidney disease, Acute Kidney Injury Network and Kidney Disease Improving Global Outcomes). We also recorded hospital and 3-months' mortality and progression to chronic kidney disease (CKD) as outcomes. RESULTS: We studied 81 patients (mean age 10.7 ± 7 years, 51.9% females) and divided them by age into (a) neonates (<120 days; n = 21; 25.9%); (b) -infants (120-365 days; n = 18; 25.9%); and (c) children (>365 days; n = 42; 53.1%). Diagnosis using different pAKI definitions resulted in differences in AKI staging. SUN reliably reflected BUN over the entire study period, regardless of treatment modality or pAKI severity. Neither pAKI staging, SUN, BUN, nor SCr were associated with mortality or progression to CKD. UO predicted all-cause mortality during the 3-months follow-up. CONCLUSION: Diagnosis of pAKI using different criteria differs in triage and staging. SUN reflects BUN particularly at higher BUN levels and allows monitoring of treatment responses. Despite the lack of predictive power of SUN to predict hard outcomes, measurement of SUN by dipstick can be used to identify, screen, and monitor pediatric patients with pAKI.

Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats.

Hesperidin is a flavanone glycoside that is found in the Citrus species and showed antioxidant, hepatoprotective as well as anticancer activity. This study investigated the effect of hesperidin on the PI3K/Akt pathway as a possible mechanism for its protective effect against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Adult Wistar rats were divided into Control group (received drug vehicle); DEN group (received 100 mg/L of DEN solution for 8 weeks), and hesperidin + DEN group (received 200 mg/kg body weight of hesperidin/day orally for 16 weeks + DEN solution as DEN group). Our findings showed that the administration of hesperidin significantly decreased the elevation in liver function enzymes, serum AFP level, and oxidative stress markers. Moreover, hesperidin administration suppressed DEN-induced upregulation of PI3K, Akt, CDK-2 protein expression, and preserved the integrity of the liver tissues from HCC formation. In conclusion, the hepatoprotective activity of hesperidin is mediated via its antioxidation and downregulation of the PI3K/Akt pathway.

A Cross-Sectional Study of Growth and Metabolic Bone Disease in a Pediatric Global Cohort Undergoing Chronic Hemodialysis.

OBJECTIVE: We sought to assess worldwide differences among pediatric patients undergoing hemodialysis. Because practices differ widely regarding nutritional resources, treatment practice, and access to renal replacement therapy, investigators from the Pediatric Investigation and Close Collaboration to examine Ongoing Life Outcomes, the pediatric subset of the MONitoring Dialysis Outcomes Cohort (PICCOLO MONDO) performed this cross-sectional study. We hypothesized that growth would be better in developed countries, possibly at the expense of bone mineral disease. STUDY DESIGN: In this cross-sectional study, we analyzed growth by height z score and recommended age-specific bone mineral metabolism markers from 225 patients <18 years of age maintained on hemodialysis, between the years of 2000 to 2012 from 21 countries in different regions. RESULTS: The patients' median age was 16 (IQR 14-17) years, and 45% were females. A height z score less than the third percentile was noted in 34% of the cohort, whereas >66% of patients reported normal heights, with patients from North America having the greatest proportion (>80%). More than 70% of the entire cohort had greater than the age-recommended levels of phosphorus, particularly in the Asia-Pacific and North America, where we also observed the greatest body mass index z score (0.99 ± 1.6) and parathyroid hormone levels (557.1 [268.4-740.5]). Below-recommended parathyroid hormone levels were noted in 26% and elevated levels in 61% of the entire sample, particularly in the Asia Pacific region. Lower-than-recommended calcium levels were noted in 36% of the entire cohort, particularly in Latin America. CONCLUSIONS: We found regional differences in growth- and age-adjusted bone mineral metabolism markers. Children from North America had the best growth, received the most dialysis, but also had the worst phosphate control and body mass index z scores.

Efficacy of contrast-enhanced FDG PET/CT in patients awaiting liver transplantation with rising alpha-fetoprotein after bridge therapy of hepatocellular carcinoma.

OBJECTIVE: To assess the diagnostic accuracy and illustrate positive findings of contrast-enhanced fluorine-18 fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) image in patients awaiting liver transplantation (LT) with rising alpha-fetoprotein (AFP) after bridge therapy of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study included 100 patients who were waiting for LT and who previously underwent locoregional therapy (LRT) of HCC. These patients had rising AFP levels on a routine follow-up examination awaiting LT. All patients underwent a contrast-enhanced 18F-FDG PET/CT examination. We calculated for each patient the maximum standardised uptake value (SUVmax) of the tumour and the ratio of the tumoral SUVmax to the normal-liver SUVmax. The diagnostic accuracy and positive contrast-enhanced findings of 18F-FDG PET/CT were established by histopathology and clinical and imaging follow-up as the reference standards. RESULTS: Contrast-enhanced 18F-FDG PET/CT detected tumour relapse in 78 patients (13 patients had intrahepatic lesions, 10 patients had extrahepatic metastases and 55 patients with combined lesions). The sensitivity, specificity and accuracy values of contrast-enhanced 18F-FDG PET/CT examination in the detection of HCC recurrence were 92.8%, 94.1% and 93%, respectively. A significant correlation was found between the AFP level and SUVmax ratio (r = 0.2283; p = 0.0224). The best threshold for 18F-FDG PET positivity was >1.21. CONCLUSION: Contrast-enhanced 18F-FDG PET/CT is a valuable tool for the detection of intrahepatic HCC recurrence or extrahepatic metastasis following rising AFP levels after LRT of HCC, and should be incorporated during routine workup awaiting LT. KEY POINTS: • 18F-FDG PET/CT is a valuable tool for the detection of HCC recurrence • 18 F-FDG PET/CT should be incorporated during routine workup awaiting liver transplantation • Significant correlation was found between AFP level and SUVmax ratio • The best threshold for 18 F-FDG PET positivity was >1.21 • The ideal cut-off value for AFP was >202.

A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3ß-Nrf2 signaling pathway.

Chlorpyrifos (CPF) is an agricultural pesticide and a potential food contaminant, which causes neurotoxicity. Here, we aimed at exploring the link between the repeated exposure to CPF and memory dysfunction in rats and the possible protective effect of kaempferol, a flavonoid with appreciable antioxidant and anti-inflammatory activities. Rats were divided into: Control group (received drug vehicles for 14 days); CPF-treated group (received subcutaneous 18 mg/kg BW of CPF daily for 14 days and CPF + Kaempferol treated group (received the same CPF dose +21 mg/kg BW of Kaempferol intraperitoneally for 14 days. On the 14th day, Y-maze and novel target recognition behavioral tests were employed to evaluate memory deficits. 24 h after the last dose of CPF, animals were sacrificed, and brain tissues were used for the determination of oxidative stress biomarkers and gene expression levels of GSK3ß and Nrf2. The results revealed that CPF-treated rats suffered from severe deterioration of spatial and non-spatial memory functions with low activities of antioxidant enzymes and acetylcholinesterase (AChE). The administration of kaempferol significantly protected against CPF-induced neuronal damage, increased the activities of antioxidant enzymes and AChE and induced a better performance in the behavioral tests. The protective effect of kaempferol was mediated through the inhibition of GSK3ß gene expression and the induction of Nrf2 expression in the brain tissues. In conclusion, the repeated exposure to CPF is associated with oxidative stress and memory deficits in rats. However, kaempferol administration effectively alleviated CPF- induced brain toxicity, possibly through the modulation of GSK3ß-Nrf2 signaling pathway.

Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Aß42) aggregates leads to sub-stoichiometric inhibition of amyloid formation.

The human molecular chaperone protein DNAJB6 was recently found to inhibit the formation of amyloid fibrils from polyglutamine peptides associated with neurodegenerative disorders such as Huntington disease. We show in the present study that DNAJB6 also inhibits amyloid formation by an even more aggregation-prone peptide (the amyloid-beta peptide, Aß42, implicated in Alzheimer disease) in a highly efficient manner. By monitoring fibril formation using Thioflavin T fluorescence and far-UV CD spectroscopy, we have found that the aggregation of Aß42 is retarded by DNAJB6 in a concentration-dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide. Quantitative kinetic analysis and immunochemistry studies suggest that the high inhibitory efficiency is due to the interactions of the chaperone with aggregated forms of Aß42 rather than the monomeric form of the peptide. This interaction prevents the growth of such species to longer fibrils and inhibits the formation of new amyloid fibrils through both primary and secondary nucleation. A low dissociation rate of DNAJB6 from Aß42 aggregates leads to its incorporation into growing fibrils and hence to its gradual depletion from solution with time. When DNAJB6 is eventually depleted, fibril proliferation takes place, but the inhibitory activity can be prolonged by introducing DNAJB6 at regular intervals during the aggregation reaction. These results reveal the highly efficacious mode of action of this molecular chaperone against protein aggregation, and demonstrate that the role of molecular chaperones can involve interactions with multiple aggregated species leading to the inhibition of both principal nucleation pathways through which aggregates are able to form.

Associations between global population health indicators and dialysis variables in the Monitoring Dialysis Outcomes (MONDO) consortium.

BACKGROUND: The number of patients receiving renal replacement therapy (RRT) increases annually and worldwide. Differences in the RRT incidence, prevalence, and modality vary between regions and countries for reasons yet to be clarified. AIMS: Gain a better understanding of the association between hemodialysis (HD)-related variables and general population global health indicators. METHODS: The present study included prevalent HD patients from 27 countries/regions from the monitoring dialysis outcomes (MONDO) database from 2006-2011. Global population health indicators were obtained from the 2014 World Health Organization report and the Human Development Index from the Human Development Report Office 2014. The Spearman rank test was used to assess the correlations between population social economic indicators and HD variables. RESULTS: A total of 84,796 prevalent HD patients were included. Their mean age was 63 (country mean 52-71), and 60% were males (country mean 52-85%). Significant correlations were found between HD demographic clusters and population education, wealth, mortality, and health indicators. The cluster of nutrition and inflammation variables were also highly correlated with population mortality, wealth, and health indicators. Finally, cardiovascular, fluid management, and dialysis adequacy clusters were associated with education, wealth, and health care resource indicators. CONCLUSION: We identified socioeconomic indicators that were correlated with dialysis variables. This hypothesis-generating study may be helpful in the analysis of how global health indicators may interfere with access to HD, treatment provision, dialytic treatment characteristics, and outcomes.

A comparative study of old versus novel psychoactive substances on craving, perceived stigma and suicidal risk among rural-dwelling patients with substance abuse.

WHAT IS KNOWN ON THE SUBJECT?: According to recent estimates, 10.4% of adults are patients with substance abuse, which is almost double the global rate. Rural areas are typically marginalized, compounded by a lack of access to mental health care, creating a startling disparity in suffering from drug use issues among rural cohorts. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Drawing on data from a descriptive comparative design would provide a distinctive picture related to the similarities and/or differences in relation to craving and how it affects perceived stigma and suicidal risk among patients using old versus novel psychoactive substances. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Substance abuse is a leading public health concern that forces nurses to encompass it into their agendas to tackle this looming problem. Addiction rehabilitation services are frequently run by nurses. They are well-versed in supporting patients during their journey to recovery and enabling them to adjust to a new lifestyle. ABSTRACT: INTRODUCTION: Substance use disorder is a leading public health concern that currently, nations regulatory agencies are grappled with. The noticeable difference in the chemical structures between old and novel psychoactive substances can result in significant clinical complications among patients with substance abuse. AIM: The study aims to compare substance craving, perceived stigma and suicidal risk among patients addicted to old and novel psychoactive substances (NPS). METHOD: A descriptive comparative design was adopted on a sample of 105 patients with substance use who completed The Penn Alcohol Craving Scale (PACS), The Perceived Stigma of Addiction Scale (PSAS) and Suicide Probability Scale (SPS). DISCUSSION: Most participants were male, with 89.5% in the old addictive substance group and 93.8% in the new addictive substance group. A statistically significant difference in the NPS groups' perceptions of stigma (23.4 ± 5.3) compared to the old addictive substance group (20.6 ± 4.2), (t = 3.037, p = .003). IMPLICATION FOR PRACTICE: Participants in the new substance group report more suicidal ideation, negative self-evaluation and hostility than those in the old substance group. Policies and practices should be tailored to the type of drug used and potential risk factors to avoid suicide among patients with substance abuse.

The feasibility of motivational interviewing on adherence to care practices, emotional intelligence, and dispositional optimism among patients with permanent pacemakers.

AIMS: Motivational interviewing (MI) has been recognized as highly effective for treating chronic diseases and various conditions, with encouraging results demonstrating its effectiveness in promoting health behaviour change. The current study was proposed to evaluate the feasibility of MI on adherence to care practices, emotional intelligence (EI), and dispositional optimism among patients with permanent pacemakers. METHODS AND RESULTS: This study was a parallel arm randomized controlled trial. Seventy clients with permanent pacemakers were randomly allocated to a six-session MI intervention (n = 35) or a waiting list control group (n = 35). A statistically significant improvement in the mean scores of adherence to care practices, EI, and dispositional optimism, along with a significant reduction in pessimism, was registered among the study group compared with the control group. CONCLUSION: Following the intervention for 1- and 2-month follow-up measurements, there were statistically significant improvements in self-care practice adherence. After 1 month of intervention, there were statistically significant gains in EI and dispositional optimism, but at the 2-month follow-up measurement, this improvement had somewhat lessened. The findings suggest that MI may be a feasible and practical approach for improving adherence to care practices, EI, and dispositional optimism in patients with permanent pacemakers. REGISTRATION: ClinicalTrials.gov: NCT05883514.

The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1ß levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Effectiveness of Rapid Response Team implementation in a tertiary hospital in Egypt: an interventional study.

BACKGROUND: Rapid response teams (RRTs) help in the early recognition of deteriorating patients in hospital wards and provide the needed management at the bedside by a qualified team. RRT implementation is still questionable because there is insufficient evidence regarding its effects. To date, according to our knowledge, no published studies have addressed the effectiveness of RRT implementation on inpatient care outcomes in Egypt. OBJECTIVE: We aimed to assess the impact of an RRT on the rates of inpatient mortality, cardiopulmonary arrest calls and unplanned intensive care unit (ICU) admission in an Egyptian tertiary hospital. METHODS: An interventional study was conducted at a university hospital. Data was evaluated for 24 months before the intervention (January 2018 till December 2019, which included 4242 admissions). The intervention was implemented for 12 months (January 2021 till December 2021), ending with postintervention evaluation of 2338 admissions. RESULTS: RRT implementation was associated with a significant reduction in inpatient mortality rate from 88.93 to 46.44 deaths per 1000 discharges (relative risk reduction (RRR)=0.48; 95% CI, 0.36 to 0.58). Inpatient cardiopulmonary arrest rate decreased from 7.41 to 1.77 calls per 1000 discharges (RRR, 0.76; 95% CI, 0.32 to 0.92), while unplanned ICU admissions decreased from 5.98 to 4.87 per 1000 discharges (RRR, 0.19; 95% CI, -0.65 to 0.60). CONCLUSIONS: RRT implementation was associated with a significantly reduced hospital inpatient mortality rate, cardiopulmonary arrest call rate as well as reduced unplanned ICU admission rate. Our results reveal that RRT can contribute to improving the quality of care in similar settings in developing countries.

Effect of quercetin-loaded poly (lactic-co-glycolic) acid nanoparticles on lipopolysaccharide-induced memory decline, oxidative stress, amyloidogenesis, neurotransmission, and Nrf2/HO-1 expression.

Neuroinflammation contributes to the pathogenesis of several neurodegenerative disorders. This study examined the neuroprotective effect of quercetin (QUR)-loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles (QUR NANO) against the neurotoxicity induced by lipopolysaccharide (LPS) in mice. A QUR NANO formulation was prepared and characterized by differential scanning calorimetry, X-ray diffraction, entrapment efficiency (EE), high-resolution transmission electron microscopy, field emission scanning electron microscopy, and in vitro drug release profile. Levels of glutathione, malondialdehyde, catalase, inducible nitric oxide synthase (iNOS), amyloid beta 42 (Aß42), ß-secretase, gamma-aminobutyric acid (GABA), and acetylcholine esterase (AChE) were measured in the mouse brain tissues. The gene expression of nuclear factor erythroid-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) were also determined. The prepared QUR NANO formulation showed 92.07 ± 3.21% EE and drug loading of 4.62 ± 0.55. It exhibited clusters of nano-spherical particles with smooth surface areas, and the loading process was confirmed. In vivo, the QUR NANO preserved the spatial memory of mice and protected the hippocampus from LPS-induced histological lesions. The QUR NANO significantly reduced the levels of malondialdehyde, iNOS, Aß42, ß-secretase, and AChE in brain tissue homogenates. Conversely, QUR NANO increased the glutathione, catalase, and GABA concentrations and upregulated the expression of Nrf-2 and HO-1 genes. Remarkably, the neuroprotective effect of QUR NANO was significantly greater than that of herbal QUR. In summary, the prepared QUR NANO formulation was efficient in mitigating LPS-induced neurotoxicity by reducing memory loss, oxidative stress, and amyloidogenesis while preserving neurotransmission and upregulating the expression of Nrf2 and HO-1 genes. This study addresses several key factors in neuroinflammatory disorders and explores the potential of QUR-loaded nanoparticles as a novel therapeutic approach to alleviate these factors.

Long non-coding RNAs: The hidden players in diabetes mellitus-related complications.

BACKGROUND AND AIM: Long non-coding RNAs (lncRNAs) have been recognized as important regulators of gene expression in various human diseases. Diabetes mellitus (DM) is a long-term metabolic disorder associated with serious macro and microvascular complications. This review discusses the potential lncRNAs involved in DM-related complications such as dysfunction of pancreatic beta islets, nephropathy, retinopathy, cardiomyopathy, and peripheral neuropathy. METHODS: An extensive literature search was conducted in the Scopus database to find information from reputed biomedical articles published on lncRNAs and diabetic complications from 2014 to 2023. All review articles were collected and statistically analyzed, and the findings were summarized. In addition, the potential lncRNAs involved in DM-related complications, molecular mechanisms, and gene targets were discussed in detail. RESULTS: The lncRNAs ANRIL, E33, MALAT1, PVT1, Erbb4-IR, Gm4419, Gm5524, MIAT, MEG3, KNCQ1OT1, Uc.48+, BC168687, HOTAIR, and NONRATT021972 were upregulated in several diabetic complications. However, ßlinc1, H19, PLUTO, MEG3, GAS5, uc.322, HOTAIR, MIAT, TUG1, CASC2, CYP4B1-PS1-001, SOX2OT, and Crnde were downregulated. Remarkably, lncRNAs MALAT1, ANRIL, MIAT, MEG3, H19, and HOTAIR were overlapping in more than one diabetic complication and were considered potential lncRNAs. CONCLUSION: Several lncRNAs are identified as regulators of DM-related complications. The expression of lncRNAs is up or downregulated depending on the disease context, target genes, and regulatory partners. However, most lncRNAs target oxidative stress, inflammation, apoptosis, fibrosis, and angiogenesis pathways to mediate their protective/pathogenic mechanism of action and contribute to DM-related complications.

Upregulation of miR-33 and miR-155 by gum acacia mitigates hyperlipidaemia and inflammation but not weight increase induced by Western diet ingestion in mice.

OBJECTIVE: This study, for the first time, investigates the effect of gum acacia (GA) on the expression of miR-33 and miR-155 and its association with the obesity and inflammation induced by Western diet (WD) consumption in mice. METHODS: Animals were divided into: normal diet (ND) group, WD group, GA group and GA + WD group. RESULTS: The WD group exhibited higher total body, liver, visceral fat weights, blood total cholesterol, triglycerides and glucose levels compared to ND group. The liver tissues showed severe inflammation and degeneration with higher hepatic TNF-α level. Interestingly, GA + WD group showed a decrease in the biochemical parameters and hepatic TNF-α level but had no effect on the weight increase. It also showed a significant upregulation of miR-33 and miR-155 compared to WD group. CONCLUSIONS: GA mitigated the hyperlipidaemia and inflammation but not weight increase induced by WD ingestion via upregulation of miR-33 and miR-155 while reducing TNF-α level.