Performance of ginger constituents against SARS-CoV-2 virus: A therapeutic and theoretical approach.

In the present research, ginger extracted compounds, namely; Gingerol {(1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone} (1), Zingerone {(4-(4-Hydroxy-3-methoxyphenyl)-2-butanone)} (2), and Shogoals {(E)-1-(4-Hydroxy-3- methoxyphenyl) dec-4-en-3-one)} (3) have been investigated as SARS-Cov-2 inhibitors. The interaction of extracted compounds with the virus's spikes may restrict the virus's reproduction or give time to the body's immune system to detect viruses, consequently producing appropriate antibodies. Gaussian 09 with a 6-311G (d, p) basis set, UCA FUKUI, MGL implement, DSV, and LigPlus software were utilized. The active sites for adsorption were identified using the total electron density (TED), FUKUI function, and Millikan charges. Furthermore, docking analysis clearly showed that the inhibition of viral replication depends on binding energy (Eb) and ligand efficiency (LE). A docking study revealed that the inhibition ability of the studied compounds on SARS-CoV-2 was in the order of 2 > 3 > 1.

A mechanoluminescent material, ZnS:Mn,Li, with enhanced brightness for visualizing dental occlusion.

Mechanoluminescent materials are characterized by high luminescence intensity, high repeatability, no external voltage activation, and a good linear relationship between stress and mechanoluminescence intensity within a certain range. Therefore, mechanoluminescent materials have attracted increasing attention from researchers in the fields of stress sensing, encryption and anti-counterfeiting, structural health monitoring, energy-saving lighting, intelligent wearable devices, and other fields. In this study, ZnS:Mn powders with different Mn2+ ratios and different ion doping were synthesized by a high-temperature solid-phase reaction, and the synthesis of various materials was characterized. Then, the optimal mechanoluminescence effect of the ZnS:1%Mn,1%Li material was obtained. The photoluminescence intensity of ZnS:1%Mn,1%Li was 16.7 times higher than that of the sample without doping with Li+, and the mechanoluminescence intensity was 1.64 times higher. Finally, polyethylene terephthalate (PET) film was combined with ZnS:Mn,Li mechanoluminescent powders to prepare flexible three-layer composite film. Based on this, a feasible strategy for the detection of temporomandibular disorders was proposed. The composite film is easy to use, economical, and safe, and has good mechanoluminescent performance, which has potential application value in the field of occlusal force detection and visualization.

A Correlational Study of Hearing Loss and Severity of Diabetic Retinopathy Among Jordanian Patients.

Background Sensorineural hearing loss (SNHL) is a common complication of diabetes, but the underlying mechanisms and risk factors are not fully understood. This study investigated the relationship between several potential risk factors and SNHL in 118 individuals previously diagnosed with diabetes mellitus type 2 (DM2). Methods We did a cross-sectional analysis of data collected from 118 patients with diabetes mellitus at multiple tertiary hospitals in the Jordanian Royal Medical Services (JRMS). The mean age was 60.57 ± 12.8 years, with 56.8% males. Demographic and clinical data were collected, including age, gender, duration of diabetes, presence and duration of hypertension, diabetic retinopathy (DR) severity, tinnitus, and comprehension inability. In addition, a hearing assessment for SNHL was performed using pure-tone audiometry at 0.5, 1, 2, 4, and 8 kHz frequencies. Goodman and Kruskal's γ test and cumulative odds ordinal logistic regression were used to analyze the relationship between these factors and hearing assessment results for SNHL. Results Goodman and Kruskal's γ test showed a statistically significant moderate and positive association between diabetic retinopathy severity and sensorineural hearing loss. Further analysis using logistic regression revealed that retinopathy severity, age, and gender were all significant predictors of hearing loss level in this population. The odds of having a higher level of hearing loss increased by 9.1% for each additional year of age and were higher for males than females. In terms of DR severity, a worsening SNHL had lower odds in individuals with no DR or mild nonproliferative DR compared to those with proliferative DR. Conclusion Our findings have important implications for managing SNHL in individuals with diabetes. They indicate that healthcare providers must closely monitor and manage the risk factors in patients with diabetes. Further research is needed to generalize better the relationship between these risk factors and SNHL, including the potential role of other factors, such as exposure to loud noise or certain medications.

Unlocking integrated waste biorefinery approach by predicting calorific value of waste biomass.

The current study analyzed the high heating values (HHVs) of various waste biomass materials intending to the effective management and more sustainable consumption of waste as clean energy source. Various biomass waste samples including date leaves, date branches, coconut leaves, grass, cooked macaroni, salad, fruit and vegetable peels, vegetable scraps, cooked food waste, paper waste, tea waste, and cardboard were characterized for proximate analysis. The results revealed that all the waste biomass were rich in organic matter (OM). The total OM for all waste biomass ranged from 79.39% to 98.17%. Likewise, the results showed that all the waste biomass resulted in lower ash content and high fixed carbon content associated with high fuel quality. Based on proximate analysis, various empirical equations (HHV=28.296-0.2887(A)-656.2/VM, HHV=18.297-0.4128(A)+35.8/FC and HHV=22.3418-0.1136(FC)-0.3983(A)) have been tested to predict HHVs. It was observed that the heterogeneous nature of various biomass waste considerably affects the HHVs and hence has different fuel characteristics. Similarly, the HHVs of waste biomass were also determined experimentally using the bomb calorimeter, and it was observed that among all the selected waste biomass, the highest HHVs (21.19 MJ kg-1) resulted in cooked food waste followed by cooked macaroni (20.25 MJ kg-1). The comparison revealed that experimental HHVs for the selected waste biomass were slightly deviated from the predicted HHVs. Based on HHVs, various thermochemical and biochemical technologies were critically overviewed to assess the suitability of waste biomass to energy products. It has been emphasized that valorizing waste-to-energy technologies provides the dual benefits of sustainable management and production of cleaner energy to reduce fossil fuels dependency. However, the key bottleneck in commercializing waste-to-energy systems requires proper waste collection, sorting, and continuous feedstock supply. Moreover, related stakeholders should be involved in designing and executing the decision-making process to facilitate the global recognition of waste biorefinery concept.

Repurposing of antibacterial compounds for suppression of Mycobacterium tuberculosis dormancy reactivation by targeting resuscitation-promoting factors B.

Tuberculosis infection has always been a global concern for public health, and the mortality rate has increased tremendously every year. The ability of the resuscitation Mycobacterium tuberculosis (Mtb) from the dormant state is one of the major reasons for the epidemic spread of tuberculosis infection, especially latent tuberculosis infection (LTBI). The element that encourages resuscitation, RpfB (resuscitation-promoting factors B), is mostly in charge of bringing Mtb out of slumber. This reason makes RpfB a promising target for developing tuberculosis drugs because of the effects of latent tuberculosis. Therefore, this work was executed using a computational three-level screening of the Selleckhem antibiotics database consisting of 462 antibiotics against the ligand binding region of the RpfB protein, followed by an estimation of binding free energy for ideal identification and confirmation of potential RpfB inhibitor. Subsequently, three antibiotic drug molecules, i.e., Amikacin hydrate (-66.87 kcal/mol), Isepamicin sulphate (-60.8 kcal/mol), and Bekanamycin (-46.89 kcal/mol), were selected on the basis of their binding free energy value for further computational studies in comparison to reference ligand, 4-benzoyl-2-nitrophenyl thiocyanate (NPT7). Based on the intermolecular interaction profiling, 200 ns molecular dynamic simulation (MD), post-simulation analysis and principal component analysis (PCA), the selected antibiotics showed substantial stability with the RpfB protein compared to the NPT7 inhibitor. Conclusively based on the computational results, the preferred drugs can be potent inhibitors of the RpfB protein, which can be further validated using in vivo research and in vitro enzyme inhibition to understand their therapeutic activity against tuberculosis infection.Communicated by Ramaswamy H. Sarma.

Impact of luminescent-ion doping on the crystallographic and photo-physical properties of the CaMoO4 nanoparticles.

Luminescent lanthanide (Ln3+ = Pr, Nd, Sm, Eu, and Tb)-ions doped calcium molybdate(CaMoO4) nanoparticles(NPs) were prepared by the polyol wet-chemical route. X-ray diffraction (XRD) pattern of all samples showed the formation of a single-phase scheelite type tetragonal structure with an average crystalline size over 21.6-33.4 nm. Thermal stability was evaluated to study the surface-anchored functional groups by weight loss measurement. Fourier transform infrared (FTIR) spectra were recorded to identify the adsorbed functional groups. Aqueous dispersibility and colloidal stability were recorded with the help of the UV/visible absorption spectra. These nanocrystals formed semi-transparent colloidal solutions after being evenly disseminated in aqueous media. The doping of the luminescent ions significantly affects the crystal structure and photoluminescence (PL) properties of the CaMoO4:Ln3+ NPs. In a comparative analysis of the absorption spectra, bandgap, Raman-active modes, and luminescent properties, they were greatly influenced by altering the dopant ion due to the variation in the atomic radius of the element. The doping of smaller atomic radius Ln3+-ions distorts the unit cell, and, subsequently, bond angle/length alters the symmetry of the host crystal. The distorted crystal lattice affects the crystalline, size, lattice parameter, band gap values, Raman active vibrational modes, and luminescent efficiency. The distorted crystal structure of the host lattices facilitates the movement of the oxygen vacancies through charge transfer, resulting in efficiently suppressed emission efficiency.Graphical abstract.

Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies.

Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, ß-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and t-res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies. The mass spectrometer was set to negative ionization mode for the quantification of quercetin and t-res. Phenomenex Luna (C18(2), 100 A, 75 × 4.6 mm, 3 µ) column was utilized to separate the analytes using an isocratic mobile phase consisting of methanol and 0.1% formic acid in water (82:18). Validation of the method was performed using various parameters, including linearity, specificity, accuracy, stability, intra-day, inter-day precision, and the matrix effect. There was no observed significant endogenous interference from the blank serum. The analysis was completed within 5.0 min for each run, and the lower limit of quantification was 5 ng/mL. The calibration curves showed a linear range with a high correlation coefficient (r2 > 0.99). The precision for intra- and inter-day assays showed relative standard deviations from 3.32% to 8.86% and 4.35% to 9.61%, respectively. The analytes in rat serum were stable during bench-top, freeze-thaw, and autosampler (-4 °C) stability studies. After oral administration, the analytes showed rapid absorption but underwent metabolism in rat liver microsomes despite being stable in simulated gastric and intestinal fluids. Intragastric administration resulted in higher absorption of quercetin and t-res, with greater Cmax, shorter half-life, and improved elimination. No prior research has been conducted on the oral pharmacokinetics and stability of anti-diabetic compounds in the Ethanolic extract of Cissus quadrangularis EECQ, making this the first report. Our findings can provide the knowledge of EECQ's bioanalysis and pharmacokinetic properties which is useful for future clinical trials.

Pancreastatin deteriorates hepatic lipid metabolism via elevating fetuin B in ovariectomized rats.

Hepatic steatosis is an important mstetabolic complication in women encountering postmenopausal phase of life. Pancreastatin (PST), has previously been investigated in diabetic and insulin resistant rodents. The present study highlighted the role of PST in ovariectomized rats. Female SD rats were ovariectomized and subsequently fed high fructose diet for 12 weeks. PST inhibitor peptide was intraperitoneally administered for 14 days and further examined for insulin resistance, glucose intolerance development, body mass composition, lipid profile detection and hepatic fibrosis. Gut microbial alterations has also been investigated. Results showed development of glucose intolerance in high fructose fed ovariectomized rats with reduced level of reproductive hormones including estradiol and progesterone. Enhanced lipid production was detected in these rats as they showed increased triglycerides, lipid accumulation in liver tissue (determined by HE staining, Oil Red O staining, Nile Red staining). Sirius Red and Masson's trichome analysis depicted positive results for fibrosis development. We also found gut microbiota alterations in fecal samples of these rats. Furthermore, PST inhibition decreased the expression of hepatic Fetuin B and resumed gut microbial diversity. PST deregulates hepatic lipid metabolism which leads to altered expression of Fetuin B in liver and gut dysbiosis in postmenopausal rats.

Novel ruthenium-doped vanadium carbide/polymeric nanohybrid sensor for acetaminophen drug detection in human blood.

The use of advanced electroactive catalysts enhances the performance of electrochemical biosensors in real-time biomonitoring and has received much attention owing to its excellent physicochemical and electrochemical possessions. In this work, a novel biosensor was developed based on the electrocatalytic activity of functionalized vanadium carbide (VC) material, including VC@ruthenium (Ru), VC@Ru-polyaniline nanoparticles (VC@Ru-PANI-NPs) as non-enzymatic nanocarriers for the fabrication of modified screen-printed electrode (SPE) to detect acetaminophen in human blood. As-prepared materials were characterized using SEM, TEM, XRD, and XPS techniques. Biosensing was carried out using cyclic voltammetry and differential pulse voltammetry techniques and has revealed imperative electrocatalytic activity. A quasi-reversible redox method of the over-potential of acetaminophen increased considerably compared with that at the modified electrode and the bare SPE. The excellent electrocatalytic behaviour of VC@Ru-PANI-NPs/SPE is attributed to its distinctive chemical and physical properties, including rapid electron transfer, striking á´«-á´« interface, and strong adsorptive capability. This electrochemical biosensor exhibits a detection limit of 0.024 µM, in a linear range of 0.1-382.72 µM with a reproducibility of 2.45 % relative standard deviation, and a good recovery from 96.69 % to 105.59 %, the acquired results ensure a better performance compared with previous reports. The enriched electrocatalytic activity of this developed biosensor is mainly credited to its high surface area, better electrical conductivity, synergistic effect, and abundant electroactive sites. The real-world utility of the VC@Ru-PANI-NPs/SPE-based sensor was ensured via the investigation of biomonitoring of acetaminophen in human blood samples with satisfactory recoveries.

Analysis of the nasopharyngeal microbiome and respiratory pathogens in COVID-19 patients from Saudi Arabia.

BACKGROUND: Infection with SARS-CoV-2 may perturb normal microbiota, leading to secondary infections that can complicate the viral disease. The aim of this study was to probe the alteration of nasopharyngeal (NP) microbiota in the context of SARS-CoV-2 infection and obesity and to identify other respiratory pathogens among COVID-19 cases that may affect patients' health. METHODS: A total of 107 NP swabs, including 22 from control subjects and 85 from COVID-19 patients, were processed for 6S amplicon sequencing. The respiratory pathogens causing secondary infections were identified by RT-PCR assay, using a kit that contained specific primers and probes combinations to amplify 33 known respiratory pathogens. RESULTS: No significant (p > 0.05) difference was observed in the alpha and beta diversity analysis, but specific taxa differed significantly between the control and COVID-19 patient groups. Genera of Sphingomonas, Kurthia, Microbacterium, Methylobacterium, Brevibacillus, Bacillus, Acinetobacter, Lactococcus, and Haemophilus was significantly abundant (p < 0.05) in COVID-19 patients compared with a healthy control group. Staphylococcus was found in relatively high abundance (35.7 %) in the COVID-19 patient groups, mainly those treated with antibiotics. A relatively high percentage of Streptococcus was detected in COVID-19 patient groups with obesity or other comorbidities. Respiratory pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Salmonella species, along with Pneumocystis jirovecii fungal species were detected by RT-PCR mainly in the COVID-19 patients. Klebsiella pneumoniae was commonly found in most of the samples from the control and COVID-19 patients. Four COVID-19 patients had viral coinfections with human adenovirus, human rhinovirus, enterovirus, and human parainfluenza virus 1. CONCLUSIONS: Overall, no substantial difference was observed in the predominant NP bacterial community, but specific taxa were significantly changed between the healthy control and COVID-19 patients. Comparatively, an increased number of respiratory pathogens were identified in COVID-19 patients, and NP colonization by K. pneumoniae was probably occurring in the local population.

Impact of diabetes mellitus and co-morbidities on mortality in patients with COVID-19: A single-center retrospective study.

OBJECTIVES: To describe the effect of diabetes mellitus (DM) on clinical outcomes of patients admitted with COVID-19 infection. METHODS: We carried out a single center, observational, retrospective study. We included adult patients with laboratory-confirmed diagnosis of COVID-19 admitted to a tertiary hospital in Jeddah, Saudi Arabia, from April 2020 to December 2020. Electronic medical records were reviewed for demographics, clinical status, hospital course, and outcome; and they were compared between the patients with or without DM. RESULTS: Out of 198 patients included in the study, 86 (43.4%) were diabetic and 112 (56.5%) were non-diabetic. Majority of the patients were males 139 (70.2%) with a mean age of 54.14±14.89 years. In-hospital mortality rate was higher in diabetic patients than in non-diabetic patients (40 vs. 32; p=0.011). The most common comorbidity was hypertension (n=95, 48%) followed by ischemic heart disease (n=35, 17.7%), chronic kidney disease (n=17, 9.6%), and bronchial asthma (n=10, 5.1%). CONCLUSION: The risk of SARS-CoV-2 infection is higher among diabetic patients; particularly, those with preexisting co-morbidities or geriatric patients. Diabetic patients are prone to a severe clinical course of COVID-19 and a significantly higher mortality rate.

Glycosylated Flavonoid Compounds as Potent CYP121 Inhibitors of Mycobacterium tuberculosis.

Due to the concerning rise in the number of multiple- and prolonged-drug-resistant (MDR and XDR) Mycobacterium tuberculosis (Mtb) strains, unprecedented demand has been created to design and develop novel therapeutic drugs with higher efficacy and safety. In this study, with a focused view on implementing an in silico drug design pipeline, a diverse set of glycosylated flavonoids were screened against the Mtb cytochrome-P450 enzyme 121 (CYP121), which is established as an approved drug target for the treatment of Mtb infection. A total of 148 glycosylated flavonoids were screened using structure-based virtual screening against the crystallized ligand, i.e., the L44 inhibitor, binding pocket in the Mtb CYP121 protein. Following this, only the top six compounds with the highest binding scores (kcal/mol) were considered for further intermolecular interaction and dynamic stability using 100 ns classical molecular dynamics simulation. These results suggested a considerable number of hydrogen and hydrophobic interactions and thermodynamic stability in comparison to the reference complex, i.e., the CYP121-L44 inhibitor. Furthermore, binding free energy via the MMGBSA method conducted on the last 10 ns interval of MD simulation trajectories revealed the substantial affinity of glycosylated compounds with Mtb CYP121 protein against reference complex. Notably, both the docked poses and residual energy decomposition via the MMGBSA method demonstrated the essential role of active residues in the interactions with glycosylated compounds by comparison with the reference complex. Collectively, this study demonstrates the viability of these screened glycosylated flavonoids as potential inhibitors of Mtb CYP121 for further experimental validation to develop a therapy for the treatment of drug-resistant Mtb strains.

Profile of the Gut Microbiome Containing Carbapenem-Resistant Enterobacteriaceae in ICU Patients.

Carbapenem-resistant Enterobacteriaceae (CRE) is a risk to public health worldwide and causes epidemic outbreaks in hospitals. The identification of alterations in the gut microbial profile can potentially serve as an early diagnostic tool to prevent harmful bacterial colonization. The purpose of this study was to characterize the gut microbiota profile of CRE-positive stool samples using 16S rRNA gene sequencing and to compare it with that of healthy control groups at King AbdulAziz University Hospital. Our results demonstrate that compared to the control group samples, the CRE-positive and CRE-negative group samples were less diverse and were dominated by a few operational taxonomic clusters of Enterococcus, Sphingomonas, and Staphylococcus. An analysis of samples from CRE-positive patients revealed Pseudomonas as the most abundant taxon. The existence of Pseudomonas in clinical samples undoubtedly indicates the development of resistance to a variety of antimicrobial drugs, with a less diverse microbiota. In our study, we found that the co-occurrence patterns of Klebsiella, Parabacteroides, Proteus and Pseudomonas differed between the CRE-negative and control stool groups.

Bacterial Community and Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Isolates from the Environment of a Health Care Facility in the Western Region of Saudi Arabia.

The escalating transmission of hospital-acquired infections, especially those due to antimicrobial-resistant bacteria, is a major health challenge worldwide. In this study, a culturomic analysis of bacterial community in a tertiary care hospital in the western region of Saudi Arabia is performed using environmental samples. The genome sequencing of four Acinetobacter baumannii was performed on isolates recovered from an intensive care unit (ICU) environment and clinical samples. A total of 361 bacterial isolates from surface and air samples were identified by MALDI-TOF technique or 16S rRNA gene sequencing. The isolates were classified into 70 distinct species, including ESKAPE pathogens. Resistance in Gram-positive isolates was mainly found to be against benzylpenicillin, azithromycin, ampicillin, and trimethoprim/sulfamethoxazole. Carbapenem- and multidrug-resistant isolates of A. baumannii and Klebsiella pneumonia were found on the ICU surfaces. Genome sequencing revealed that the carbapenem-resistant A. baumannii isolate from ICU environment was linked with those of clinical origin. The isolate Ab133-HEnv was classified as a novel sequence type (ST2528) based on a new allele of Oxf_gdhB-286. Three beta-lactam-antibiotic-resistance genes, blaADC-25, blaOXA-23, and blaOXA-66, were found in most of the analyzed genomes. Collectively, the results of this study highlight the spread of antimicrobial-resistant nosocomial pathogens in a health care facility in Saudi Arabia.

Angiotensin (1-7) protects against renal ischemia-reperfusion injury via regulating expression of NRF2 and microRNAs in Fisher 344 rats.

Ischemia-reperfusion (I/R) is considered the primary cause of acute kidney injury and is higher among older individuals. Although ischemic episodes are hard to predict and prevent, detrimental ischemic effects could be mitigated by exogenous intervention. This study aimed to identify the protective role of angiotensin (1-7) [ANG(1-7)] against I/R-induced renal injury in adult versus aged rats. Adult and aged male Fisher 344 rats were subjected to 40 min of bilateral renal ischemia followed by 28 days of reperfusion. ANG(1-7) was administered intraperitoneally in ischemic rats for 28 days with or without the Mas receptor antagonist A779. I/R increased blood pressure, plasma creatinine, urinary 8-isoprostane, and renal infiltration of pro- and anti-inflammatory macrophages and reduced glomerular filtration rate in both adult and aged rats compared with sham rats. In addition to causing glomerular sclerosis and tubular damage, I/R increased the expression of the following pathogenic miRNAs: miR-20a-5p, miR-21-5p, miR-24-3p, and miR-194-5p in both age groups. ANG(1-7) treatment of ischemic rats mitigated oxidative stress and renal inflammation, restored renal structure and function, and reduced high blood pressure. Also, ANG(1-7) suppressed the expression of pathogenic miRNAs. In addition, ANG(1-7) treatment of I/R rats increased the expression of the redox-sensitive transcription factor nuclear factor-erythroid factor 2-related factor 2 (NRF2) and phase II antioxidant enzymes. The beneficial effects of ANG(1-7) were sensitive to A779. Collectively, these data suggest that ANG(1-7) associated with NRF2 activation could alleviate post-I/R-induced kidney injury, and therefore serve as a potential therapeutic compound to protect against biochemical and morphological pathologies of I/R in both adults and aged populations.NEW & NOTEWORTHY This is the first study to show that ANG(1-7) via Mas receptors could activate the redox-sensitive nuclear factor-erythroid factor 2-related factor 2 (NRF2)-phase II antioxidant system and protect against ischemia-reperfusion (I/R)-induced renal injury, identifying ANG(1-7), Mas receptor agonists, or NRF2 activators as potential therapeutic interventions to protect against renal and cardiovascular diseases. Moreover, miRNAs have differential expression in adult versus aged rats, and I/R modulates miRNA expression in both age groups, indicating their involvement in kidney disease.

Facile synthesized NaGdF4 :Yb,Er peanut-shaped, highly biocompatible, colloidal upconversion nanospheres.

A facile method was used for the synthesis of peanut-shaped very emissive NaGdF4 :Yb, Er upconversion nanospheres (UCNSs) at lower temperatures with uniform size distribution. Crystallographic structure, phase purity, morphology, thermal robustness, biocompatibility, colloidal stability, surface chemistry, optical properties, and luminesce properties were explored by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential, thermogravimetric/differential thermal analysis (TGA/DTA), Fourier-transform infrared (FTIR), ultraviolet (UV)-visible and photoluminescence spectroscopic tools. XRD pattern verified the construction of a single-phase, highly-crystalline NaGdF4 phase with a hexagonal structure. Peanut-shaped morphology of the sample was obtained from SEM micrographs which were validated from high-resolution TEM images, to have an equatorial diameter of 170 to 200 nm and a length of 220 to 230 nm, with irregular size, monodispersed, porous structure, and rough surface of the particles. The positive zeta potential value exhibited good biocompatibility along with high colloidal stability as observed from the absorption spectrum. The prepared UCNSs revealed high dispersibility, irregular size peanut-shaped morphology, rough surface, good colloidal stability, and excellent biocompatibility in aqueous media. A hexagonal phase NaGdF4 doped with ytterbium (Yb) and erbium (Er) UCNSs revealed the characteristics of highly dominant emissions located at 520-525, 538-550, and 659-668 nm corresponding to the 2 H11/2 → 4 I15/2 , 4 S3/2 → 4 I15/2 , and 4 F9/2 → 4 I15/2 transition of Er3+ ions, respectively, as a result of energy transfer from sensitizer Yb3+ ion to emitter Er3+ ion.

Development and Evaluation of Biocompatible Topical Petrolatum-liquid Crystal Formulations with Enhanced Skin Permeation Properties.

Transdermal administration represents a major advancement over traditional pharmaceutical dosing methods. However, a frequent issue is inadequate penetration of the active medicinal component through the skin. As a result, in the current research, we assessed the utility of newly developed petrolatum-liquid crystal (LC) ointment formulations and characterized their biocompatibility and function in the transdermal drug delivery system. To begin, we made petrolatum-LC formulations using p-aminobenzoic acid (PABA) as a hydrophilic model molecule. The viscosity, small-angle X-ray scattering (SAXS), particle diameters, and z-potential were measured to assess the physicochemical properties of the formulations. A dialysis release technique was used to evaluate medication release from petrolatum-LC formulations. In vitro testing was performed to determine the potential to enhance skin penetration. The biocompatibility of the produced formulations was further tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and single-cell gel electrophoresis. According to the results, the novel petrolatum-LC formulations are biocompatible and effective in forming hexosomes. PABA skin penetration was significantly enhanced by the new petrolatum-LC formulations. According to this study, petroleum-LC formulations are more efficient than commercial petrolatum in terms of skin permeability improvement and PABA skin concentration.

Age-Related Mitochondrial Impairment and Renal Injury Is Ameliorated by Sulforaphane via Activation of Transcription Factor NRF2.

Age is one of the major risk factors for the development of chronic pathologies, including kidney diseases. Oxidative stress and mitochondrial dysfunction play a pathogenic role in aging kidney disease. Transcription factor NRF2, a master regulator of redox homeostasis, is altered during aging, but the exact implications of altered NRF2 signaling on age-related renal mitochondrial impairment are not yet clear. Herein, we investigated the role of sulforaphane, a well-known NRF2 activator, on age-related mitochondrial and kidney dysfunction. Young (2-4 month) and aged (20-24 month) male Fischer 344 rats were treated with sulforaphane (15 mg/kg body wt/day) in drinking water for four weeks. We observed significant impairment in renal cortical mitochondrial function along with perturbed redox homeostasis, decreased kidney function and marked impairment in NRF2 signaling in aged Fischer 344 rats. Sulforaphane significantly improved mitochondrial function and ameliorated kidney injury by increasing cortical NRF2 expression and activity and decreasing protein expression of KEAP1, an NRF2 repressor. Sulforaphane treatment did not affect the renal NRF2 expression or activity and mitochondrial function in young rats. Taken together, our results provide novel insights into the protective role of the NRF2 pathway in kidneys during aging and highlight the therapeutic potential of sulforaphane in mitigating kidney dysfunction in elders.

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings.

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood-plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood-plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.

In situ Polymerization of Polyaniline/Samarium Oxide - Anatase Titanium Dioxide (PANI/Sm2O3-TiO2) Nanocomposite: Structure, Thermal and Dielectric Constant Supercapacitor Application Study.

Pure and varying weigh ratio of Sm2O3-TiO2 modified polyaniline nanocomposite has been successfully synthesized using in situ polymerization of aniline solution with Sm2O3-TiO2 binary oxide. The nanocomposite have been characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), X-photoelectron microscopy (XPS), Field emission-scanning electron microscope (FE-SEM), transmission electron microscopy (TEM) thermogravimetric analysis (TGA) and LCR meter. The XRD results show synthesis anatase TiO2 phase with tetragonal structure and (monoclinic and cubic) mixture structure of Sm2O3. The FE-SEM and TEM measurements appear preparing spherical nanoparticles that covered fiber morphology of polyaniline and successfully in situ polymerization process. The TGA measurements are obtain high thermal stability for polyaniline after incorporation by Sm2O3-TiO2 binary oxide nanoparticles. LCR measurement is obtained that the DC conductivity, dielectric constant and dielectric loss of nanocomposite is larger than pure polyaniline and the electric properties increase with increasing the concentration of nanoparticles.