Renal resistive index by point of care ultrasound to predict sepsis associated acute kidney injury in critically ill children.

BACKGROUND: Sepsis associated acute kidney injury (AKI) is linked with adverse outcomes in the PICU. Doppler-based renal resistive index (RRI) has shown promising results in adults for prediction of AKI. We aimed to explore the performance of RRI in children with sepsis. METHODS: This prospective observational study (March - November 2022) included children aged 1-12 years with sepsis admitted to the PICU. RRI and urine neutrophil gelatinase associated lipocalin (NGAL) were measured within 12 h of admission. Children were followed up for 3 days. AKI (new and persistent) was defined as any child with KDIGO stage 2 or 3 AKI on day 3. RESULTS: We enrolled 90 children but included 79 in final analysis. Two thirds (n = 53, 67%) had septic shock. Median (IQR) age was 6.2 years (4.1-9.2). RRI decreased with increasing age. Twenty-six (33%) children had AKI on day 3. Mean (SD) RRI was higher in the AKI group [0.72 (0.08) vs. 0.65 (0.07), p < 0.001].The area under ROC curve for RRI to detect AKI among the 1-4 year old group was 0.75 (95% CI:0.51, 0.98; p = 0.05) and among the 5-12 year old group was 0.76 (0.62, 0.89; p = 0.001). An RRI 0.71 predicted AKI with 100% sensitivity and 46.2% specificity among the 1-4-year-old group and RRI 0.69 predicted it with 70% sensitivity and 77.5% specificity in the 5-12-year-old group. RRI and eGFR at admission were independent predictors of AKI on multivariable analysis. Urine NGAL 94.8 ng/ml predicted AKI with 76.9% sensitivity and 77.4% specificity and AUROC was 0.74 (0.62, 0.86) among the 1-12-year-old group. CONCLUSIONS: RRI values varied with age. RRI showed good diagnostic accuracy to detect new/persistent AKI on day 3 in children with sepsis; however, it was less precise as an independent predictor.

Nursing Intervention Strategies and Their Effectiveness on Restless Leg Syndrome and Psycho-Social Problems in Chronic Kidney Disease Patients.

Background: Chronic kidney disease is a global health problem affecting 843.6 million people with 1 million deaths and the 12th leading non-communicable cause of death worldwide. Insomnia is a disturbing problem found in chronic kidney disease patients, leading to physiological problems like fatigue, edema, and restless leg syndrome most of the time. The objective of this study was to assess the effectiveness of nursing intervention strategies on physiological and psycho-social problems. Materials and Methods: A quantitative research approach with quasi-experimental pre-test and post-test design was used to assess the effectiveness of nursing intervention strategies on physiological and psycho-social problems among 30 chronic kidney disease patients, 15 in control and experimental each, admitted in a selected hospital of Punjab. Convenience sampling was used to assign the samples, and data were collected through an interview schedule by using standardized scales. IEC number: 2017/08/5051. Results: The result of the study showed that the baseline restless leg syndrome mean score was 9.67, whereas the psycho-social problem baseline mean score was 79.80, and after post-test, the mean score was reduced to 7.67 in physiological and 66.87 in psycho-social problems in the experimental group. Intervention was found to be effective in reduction of physiological and psycho-social symptoms of chronic kidney disease patients significantly (P ≤ 0.05). Conclusions: The study showed that nursing intervention strategies were effective in reduction of physiological and psycho-social symptoms.

Pearl millet flour and green gram milk based probiotic beverage.

The probiotic beverage was developed using germinated and ungerminated pearl millet flour and green gram milk. The germinated and ungerminated pearl millet flour was added to green gram milk at different concentrations (0.5-2.5 %) along with sugar and cardamom. The mixtures were then inoculated with probiotic bacteria Lactobacillus acidophilus incubated at 37 °C for 6 h. Characterization of probiotic beverages was carried out during storage at (4 ± 1)°C for 21 days. The germinated flour beverage had high acidity as compared to the ungerminated flour beverage. The probiotic count in germinated and ungerminated flour beverages ranged from 8.19 to 8.77 × 107 and 8.04 to 8.52 × 107 log CFU/mL, respectively. Antioxidant activity, polyphenol content increased with an increase in the concentration of flour in the beverage. The LC-MS analysis found the existence of vitexin and isovitexin as the main polyphenolic compounds in the probiotic beverage. Non-dairy probiotic beverage prepared with 0.5 % germinated millet flour gave the best taste, color, texture, and rheological properties.

Estimation of dietary intake of sodium, potassium, phosphorus and protein in healthy Indian population and patients with chronic kidney disease.

Introduction: Poor nutritious diet is a major risk element for non-communicable diseases (NCD), which are of considerable public health concern. Given the diverse dietary patterns in India, precise determination of nutrient consumption is crucial for disease management. The present study assessed the dietary intake of sodium, potassium, protein, and phosphorus among North Indians. Methods: This cross-sectional study included healthy adults and adults with stage 2 to 4 chronic kidney disease (CKD). We analysed sodium, protein, potassium and phosphorus intakes using one-time 24-h urinary excretion. Dietary intake was also analysed in subgroups based on sex, body mass index, blood pressure and abdominal obesity. We evaluated the performance of various equations available to estimate sodium intake using a spot urine sample with respect to the sodium excretion measured in a 24-h urine sample. Descriptive statistics was used along with t-test for statistical significance. Results: A total of 404 subjects (182 adult healthy subjects and 222 adults with CKD) with a mean age of 47.01 ± 11.46 years were studied. Mean dietary intakes of sodium, salt, potassium, protein and phosphorus were 2.94 ± 1.68 g/day, 7.42 ± 4.24 g/day, 1.43 ± 0.59 g/day, 47.67 ± 14.73 g/day and 0.86 ± 0.39 g/day, respectively. There were no differences in nutrient consumption between adults who were healthy and those with CKD. Consumption of sodium, salt, protein, potassium, and phosphorus among healthy population vs. those with CKD were 2.81 ± 1.60 vs. 3.05 ± 1.73 g/day (p = 0.152), 7.08 ± 4.04 vs. 7.70 ± 4.37 g/day (p = 0.143), 47.16 ± 14.59 vs. 48.08 ± 14.86 g/day (p = 0.532), 1.38 ± 0.59 vs. 1.48 ± 0.58 g/day (p = 0.087) and 0.86 ± 0.41 vs. 0.87 ± 0.37 g/day (p = 0.738), respectively. Men had higher consumption of these nutrients than women. Compared to non-hypertensives, hypertensive subjects had higher consumption of salt (8.23 ± 4.89 vs. 6.84 ± 3.59 g/day, p = 0.002) and potassium (1.51 ± 0.63 vs. 1.38 ± 0.55 g/day, p = 0.024), however, no difference were found in protein and phosphorus intakes. In terms of performance of equations used to estimate 24-h sodium intake from spot urinary sodium concentration against the measured 24-h urinary sodium excretion, INTERSALT 2 equation exhibited the least bias [1.08 (95% CI, -5.50 to 7.66)]. Conclusion: The study shows higher-than-recommended salt and lower-than-recommended potassium intake in the north Indian population compared to those recommended by guidelines. The dietary protein intake is below the recommended dietary allowance. These findings help the development of targeted policies for dietary modification to reduce the risk of the development and progression of CKD.

Augmented mannose-binding lectin levels in primary membranous nephropathy: A pilot study.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.

Augmenting the quality and storage stability of soymilk by incorporation of untreated and ozonated oat 1,4-ß-D-glucan.

The study aimed to improve the quality and storage stability of novel plant-based soymilk with the incorporation of untreated (UtßG) and modified oat derived 1,4-ß-D-glucan (OzßG) at varying concentrations (0, 1, and 2 % labelled as S0, S1 and S2). The treated soymilk was characterized for physical, chemical, nutritional, rheological, particle size, zeta potential, sensory and storage stability characteristics. The results revealed that 1, 4-ß-D-glucan incorporation increased the acidity (0.67 to 0.73 %), viscosity (3.4 to 4.7 Cp) and ash content (0.74 to 0.92 %), however color remains natural. The frequency sweep and shear experiments showed that the 1,4-ß-D-glucan modified the rheological parameters of the soymilk. The sensory analysis (n = 30) indicated that texture, mouthfeel and overall acceptability (8.38). Compared to OzßG-treated soymilk, UtßG soymilk, especially S2, exhibited superior thickening and rheological properties. The storage study indicated minimal phase separation in 1,4-ß-D-glucan-incorporated samples, maintaining stability for 15 days under refrigerated conditions without compromising overall quality. Thus, this study provides valuable insights into the potential application of 1,4-ß-D-glucan for improving the technological quality of soymilk that highlights possible implications for its commercialization potential.

IL-23/IL-17 in a Paradoxical Association with Primary Membranous Nephropathy.

Primary membranous nephropathy (PMN), an autoimmune disease, is the most common cause of nephrotic syndrome in middle-aged non-diabetic adults. PMN pathophysiology includes Th1/Th2 paradigm. The IL-23/IL-17 pathway is implicated in autoimmune kidney disorders, but no study has examined its relationship with PMN. In several unrelated studies, PMN patients reported to have paradoxical IL-17 levels. This manuscript describes the best possible association of IL-23/IL-17 axis with PMN. Biopsy-proven PMN patients and age, gender-matched healthy controls were enrolled. Serum-PLA2R (Euroimmune, Germany), IL-23 and IL-17 (R&D; USA), was measured using ELISA along with biochemical parameters. Appropriate statistical tools were used for analysis. One hundred eighty-nine PMN patients (mean age 41.70 ± 12.53 years) and 100 controls (mean age 43.92 ± 10.93 years) were identified. One hundred forty were PLA2R-related. PMN patients had median proteinuria, serum albumin, and creatinine of 6.12 (3.875, 9.23) g/day, 2.32 (1.96, 2.9) g/dl, and 0.89 (0.7, 1.1) mg/dl, respectively. IL-17, but not IL-23, was significantly increased in PMN patients compared to controls (IL-17, median: 12.07 pg/ml (9.75, 24.56) vs median: 9.75 pg/ml (8.23, 17.03) p = 0.0002); (IL23, median: 6.04 pg/ml (4.22, 10.82) vs median: 5.46 pg/ml (3.34, 9.96) p = 0.142). IL-17 and IL-23 correlated significantly (p 0.05) in PMN patients, and similar trend was seen when grouped into PLA2R-related and -unrelated groups. The levels of IL-23 (p = 0.057) and IL-17 (p = 0.004) were high in MN patients that did not respond to the treatment. The current finding may indicate or suggest the involvement of IL-23/IL-17 PMN pathogenesis. A comprehensive investigation is needed to evaluate IL-23/IL-17 axis with renal infiltrating immune cells, and external stimuli.

Effect of cooking and storage temperature on resistant starch in commonly consumed Indian wheat products and its effect upon blood glucose level.

Background/objectives: The health benefits provided by resistant starch have been well documented; however, few studies are available on the resistant starch content of wheat products in India. Moreover, few studies have examined the in vivo efficacy of resistant starch in wheat products in improving glucose levels. This study was conducted to evaluate the effect of cooking and storage temperature on the formation of resistant starch in Indian wheat products and its effect on blood glucose levels in humans and rats. Methods: Wheat products were prepared by common cooking methods including roasting (Chapati), boiling (Dalia), Shallow frying (Paratha), and Deep frying (Poori). They were then stored at different temperatures including freshly prepared within 1 h (T1), stored for 24 h at room temperature (20-22°C) (T2), kept at 4°C for 24 h (T3) and reheated after storing at 4°C for 24 h (T4). The products were then analyzed for proximate composition (moisture, crude protein, crude fat, ash crude fibre, and carbohydrates). The effect of different cooking methods and storage temperatures on Resistant, non-resistant and total starch, total dietary fibre (soluble and insoluble), in vitro starch digestion rate (rapidly and slowly digestible starch), amylose and amylopectin content were analysed using standard operating procedures. The effect of products found to have higher resistant starch was studied on the post prandial blood glucose response of 10 healthy individuals using change in by analysing their glycemic index and glycemic load of wheat products. Further, the effect of resistant starch rich chapati on the blood glucose level of rats was also studied. Tukey's test in factorial CRD was used to assess the effect of cooking and temperature on various parameters. Results: The amount of resistant starch was found to be high in dalia (boiling, 7.74%), followed by parantha (shallow frying, 4.94%), chapati (roasting, 2.77%) and poori (deep frying 2.47%). Under different storage temperatures, it was found high in products stored at 4°C (T3), followed by products stored at room temperature (T2), reheated products (T4) and lesser in freshly prepared products (T1). The glycemic index and glycemic load were found low in chapati (43, 32.3) and dalia (41.1, 28.6) stored at 4°C (T3) compared to others. The resistant starch content found in chapati stored at T3 was found to be more effective at reducing blood glucose levels in rats from 291.0 mg/100 mL to 225.2 mg/100 mL in 28 days of study compared to freshly prepared chapati (T1) and stored at room temperature (T2). Conclusion: Cooking methods including boiling, roasting and shallow frying increased the amount of resistant starch in foods, but cooking methods such as deep frying decreased the amount of resistant starch in food. Products stored at 4°C and at room temperature for 24 h increased the amount of resistant starch whereas the products that were freshly cooked and reheated decreased the amount of resistant starch in foods. At 4°C the stored products have a high amount of insoluble dietary fibre, slowly digestible starch, high amylose and low glycemic index. They take time to digest, meaning that they slowly increase blood glucose levels. The effect of insoluble dietary fibre and resistant starch in the inhibition of glucose diffusion in the small intestine is suggested to be due to the absorption or inclusion of the smaller sugar molecules. In vivo research showed that fibre and resistant starch in the digestive system of rats acts as the main factors in slowing glucose absorption and reducing a rise in blood glucose levels by promoting glycogen synthesis and inhibition of gluconeogenesis.

Fatty acid profiling and oxidative stability of biscuits available in the market of the city of Ludhiana, India.

India has occupied third position in biscuit manufacturing with an average production of 1.95 million tonnes. The major ingredients in biscuit manufacturing are refined wheat flour, sugar and fat. Fat to be used must be chosen carefully as it affects quality of final product in terms of fatty acid composition and oxidative stability. Therefore, the present work was planned to study fatty acid profile of highly consumed baked products of biscuit family such as biscuits and cookies available in market. The study was carried out to do fatty acid profiling of a range of highly consumed baked products of biscuit family as a primary objective and also, to determine oxidative stability of these products by analysing peroxide value and free fatty acid content. The most commonly consumed packaged and unpackaged bakery products were selected and were bought from the local market of Ludhiana city on the basis of a survey conducted on 200 subjects. The selected products were analysed for fatty acid composition and oxidative stability using standard methods. Fatty acid profiling of 22 bakery products of biscuit family was done. Palmitic acid was the most abundant among all fatty acids in packaged and unpackaged samples. Peroxide value of all the products even after storage period of three months was found below the permissible limits (< 10 meq/kg). Free fatty acids value of all the products also did not cross acceptable level of 0.5 percent. Out of total selected eight brands, six were national and two were international. Amount of palmitic acid was higher in the products belonging to local brands.

Camouflage Detection and Its Association with Cognitive Style: A Functional Connectivity Study.

Background: Individual differences exist in performance in tasks that require visual search, such as camouflage detection (CD). Field dependence/independence (FD/I), as assessed using the Group Embedded Figures Test (GEFT), is an extensively studied dimension of cognitive style that classifies participants based on their visual perceptual styles. Materials and Methods: In the present study, we utilized fMRI on 46 healthy participants to investigate the underlying neural mechanisms specific to the cognitive styles of FD/FI while performing a CD task using both activation magnitude and an exploratory functional connectivity (FC) analysis. Group differences between high and low performers on the two extremes of the accuracy continuum of GEFT were studied. Results: No statistically significant group differences were observed using whole-brain voxel-wise comparison. However, the exploratory FC analysis revealed an enhanced communication between various regions subserving the cognitive traits required for visual search by FI participants over and above their FD counterparts. Conclusion: These enhanced connectivities suggest additional recruitment of cognitive functions to provide computational support that might facilitate superior performance in CD task by the participants who display a field-independent cognitive style.

Acute Oxidative Stress Can Paradoxically Suppress Human NRF2 Protein Synthesis by Inhibiting Global Protein Translation.

The NRF2 transcription factor is a master regulator of the cellular oxidant/electrophile response and a drug target for the prevention/treatment of chronic diseases. A major mechanism of NRF2 activation is its escape from rapid degradation, and newly synthesized NRF2 induces cytoprotective protein expression through its cognate antioxidant response elements (AREs). However, oxidative stress can also inhibit global protein translation, thereby potentially inhibiting NRF2 protein accumulation. H2O2 has been shown to be a relatively weak inducer of NRF2 in comparison with electrophiles. In the current study, we evaluated whether levels of H2O2 that activate the NRF2/ARE pathway inhibit NRF2 protein synthesis in HaCaT keratinocytes. A weak maximum induction was observed for H2O2 in comparison with electrophiles, both for NRF2 protein accumulation and ARE reporter activation (~10-fold compared to ≥100-fold activation). At similar H2O2 concentrations, both NRF2 protein synthesis and global protein synthesis were inhibited. The manganese porphyrin antioxidant MnTMPyP rescued both global protein synthesis and NRF2 protein synthesis from H2O2 inhibition and increased ARE reporter activation. Similar results were observed for the diphenol di-tert-butylhydroquinone (dtBHQ). In conclusion, induction of the NRF2/ARE pathway by H2O2 and dtBHQ-derived oxidative species can be limited by inhibition of NRF2 protein synthesis, likely by arrest of global protein synthesis.

Antimicrobial-Resistant Escherichia coli, Enterobacter cloacae, Enterococcus faecium, and Salmonella Kentucky Harboring Aminoglycoside and Beta-Lactam Resistance Genes in Raw Meat-Based Dog Diets, USA.

The practice of feeding raw meat-based diets to dogs has grown in popularity worldwide in recent years. However, there are public health risks in handling and feeding raw meat-based dog diets (RMDDs) to dogs since there are no pathogen reduction steps to reduce the microbial load, which may include antimicrobial-resistant pathogenic bacteria. A total of 100 RMDDs from 63 suppliers were sampled, and selective media were used to isolate bacteria from the diets. Bacterial identification, antimicrobial susceptibility testing, and whole-genome sequencing (WGS) were conducted to identify antimicrobial resistance (AMR). The primary meat sources for RMDDs included in this study were poultry (37%) and beef (24%). Frozen-dry was the main method of product production (68%). In total, 52 true and opportunistic pathogens, including Enterobacterales (mainly Escherichia coli, Enterobacter cloacae) and Enterococcus faecium, were obtained from 30 RMDDs. Resistance was identified to 19 of 28 antimicrobials tested, including amoxicillin/clavulanic acid (23/52, 44%), ampicillin (19/52, 37%), cephalexin (16/52, 31%), tetracycline (7/52, 13%), marbofloxacin (7/52, 13%), and cefazolin (6/52, 12%). All 19 bacterial isolates submitted for WGS harbored at least one type of AMR gene. The identified AMR genes were found to mediate resistance to aminoglycoside (gentamicin, streptomycin, amikacin/kanamycin, gentamicin/kanamycin/tobramycin), macrolide, beta-lactam (carbapenem, cephalosporin), tetracycline, fosfomycin, quinolone, phenicol/quinolone, and sulfonamide. In conclusion, the results of this study suggest that feeding and handling RMDDs may pose a significant public health risk due to the presence of antimicrobial-resistant pathogens, and further research and intervention may be necessary to minimize these risks.

Lyophilized mixed micelles of exemestane: A novel paradigm to improve its absorption and anticancer activity.

The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp-EXE-MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1 H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT-PCR and Western blot analysis) in MCF-7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp-EXE-MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp-EXE-MMs showed sustained release behavior as compared to EXE-suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase-3, p53, and CYP19A1 in MCF-7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp-EXE-MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.

Assessment of anti-psoriatic activity of bakuchiol-loaded solid lipid nanoparticles-based gel: design, characterization, and mechanistic insight via NF-kB signaling pathway.

The aim of the current study is to evaluate the anti-psoriatic potential of bakuchiol (Bak) loaded solid lipid nanoparticles (SLNs) via modulating inflammatory and oxidative pathways. Bak-loaded SLNs were prepared using hot homogenization method and characterized by various spectroscopic techniques. Bak-SLNs suspension was formulated into gel using Carbopol. Different in vivo assays were executed to explore the role of inflammatory markers and oxidative enzymes in psoriasis. DLS (dynamic light scattering) analysis showed suitable particle size, zeta potential, and polydispersity index (PDI) of developed formulation. TEM (transmission electron microscopy) reveal the spherical shape of Bak-SLNs particles. The release studies confirmed the sustained release of Bak-SLNs-based gel. UV-B-induced psoriatic Wistar rat model showed significant anti-psoriatic effect of Bak via regulating inflammatory markers (NF-kB, IL-6, IL-4, and IL-10) and levels of anti-oxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-S-transferase (GST). Furthermore, RT-qPCR analysis confirms that Bak downregulates the expression of inflammatory markers, while histology and immunohistology results also confirm the anti-psoriatic effect of Bak. The study indicates that Bak-loaded SLNs-based gel significantly downregulates the level of cytokines and interleukins involve in NF-kB signaling cascade; hence, it can prove to be a novel therapeutic approach to cure psoriasis.

Neuromodulatory effect of 4-(methylthio)butyl isothiocyanate against 3-nitropropionic acid induced oxidative impairments in human dopaminergic SH-SY5Y cells via BDNF/CREB/TrkB pathway.

Mitochondrial impairment, energetic crisis and elevated oxidative stress have been demonstrated to play a pivotal role in the pathological processes of Huntington's disease (HD). 3-Nitropropionic acid (3-NPA) is a natural neurotoxin that mimics the neurological dysfunctions, mitochondrial impairments and oxidative imbalance of HD. The current investigation was undertaken to demonstrate the neuroprotective effect of 4-(methylthio)butyl isothiocyanate (4-MTBITC) against the 3-NPA induced neurotoxicity in human dopaminergic SH-SY5Y cells. The experimental evidence of oxidative DNA damage by 3-NPA was elucidated by pBR322 DNA nicking assay. In contrast, the 4-MTBITC considerably attenuated the DNA damage, suggesting its free radical scavenging action against 3-NPA and Fenton's reagent. The dose and time-dependent increase of 3-NPA revealed its neurotoxic dose as 0.5 mM after 24 h of treatment of SH-SY5Y cells in MTT assay. In order to determine the optimal dose at which 4-MTBITC protects cell death, the 3-NPA (IC50) induced cells were pretreated with different concentrations of 4-MTBITC for 1 h. The neuroprotective dose of 4-MTBITC against 3-NPA was found to be 0.25 µM. Additionally, the elevated GSH levels in cells treated with 4-MTBITC indicate its propensity to eliminate reactive species generated as a result of 3-NPA-induced mitochondrial dysfunction. Likewise, it was determined through microscopic and flow cytometric experiments that 3-NPA's induced overproduction of reactive species and a decline in mitochondrial membrane potential (MMP) could be efficiently prevented by pre-treating cells with 4-MTBITC. To elucidate the underlying molecular mechanism, the RT-qPCR analysis revealed that the pre-treatment of 4-MTBITC effectively protected neuronal cells against 3-NPA-induced cell death by preventing Caspase-3 activation, Brain-derived neurotrophic factor (BDNF) upregulation, activation of cAMP response element-binding protein (CREB) and Nrf2 induction. Together, our findings lend credence to the idea that pre-treatment with 4-MTBITC reduced 3-NPA-induced neurotoxicity by lowering redox impairment, apoptotic state, and mitochondrial dysfunction. The present work, in conclusion, presented the first proof that the phytoconstituent 4-MTBITC supports the antioxidant system, BDNF/TrkB/CREB signaling, and neuronal survival in dopaminergic SH-SY5Y cells against 3-NPA-induced oxidative deficits.

Role of polyphenolic compounds and their nanoformulations: a comprehensive review on cross-talk between chronic kidney and cardiovascular diseases.

Chronic kidney disease (CKD) affects a huge portion of the world's population and frequently leads to cardiovascular diseases (CVDs). It might be because of common risk factors between chronic kidney disease and cardiovascular diseases. Renal dysfunction caused by chronic kidney disease creates oxidative stress which in turn leads to cardiovascular diseases. Oxidative stress causes endothelial dysfunction and inflammation in heart which results in atherosclerosis. It ends in clogging of veins and arteries that causes cardiac stroke and myocardial infarction. To develop an innovative therapeutic approach and new drugs to treat these diseases, it is important to understand the pathophysiological mechanism behind the CKD and CVDs and their interrelationship. Natural phytoconstituents of plants such as polyphenolic compounds are well known for their medicinal value. Polyphenols are plant secondary metabolites with immense antioxidant properties, which can protect from free radical damage. Nowadays, polyphenols are generating a lot of buzz in the scientific community because of their potential health benefits especially in the case of heart and kidney diseases. This review provides a detailed account of the pathophysiological link between CKD and CVDs and the pharmacological potential of polyphenols and their nanoformulations in promoting cardiovascular and renal health.