Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis.

Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.

Correlation of APOE polymorphism, expression, and plasma levels with cardiac comorbidities among lipodystrophy in HIV-infected patients.

Lipodystrophy in HIV-infectedpatients(LDHIV) includes morphological and metabolic abnormalities, including lipid and glucose metabolism. ApoE plays a role in the transport and clearance of lipoprotein. In the general population, ApoE 112 (rs429358) and 158 (rs7412) polymorphisms were linked to severe dyslipidemia. Therefore, we investigated ApoE polymorphism using PCR-RFLP in 200 HIV patients (100 with HIV-associated lipodystrophy (HIVLD), 100 without HIVLD), as well as 100 healthy controls. We also assessed ApoE expression using qRT-PCR and measured its level using ELISA. The APOE 4/4, 3/4, and 2/4 genotypes have been associated with a decreased risk of HIV-1 infection. (P=0.0001, OR=0.18; P=0.006, OR=0.87; P=0.006, OR=0.09) when compared between HIV-positive individuals and healthy controls. Conversely, APOE allele 2 was linked to a higher risk of acquiring HIV-1 (P=0.03, OR=3.02). APOE allele 2 was linked to a higher likelihood of HIVLD severity when compared between patients with and without HIVLD(P=0.05, OR=2.82). When comparing patients with HIVLD to healthy controls, the APOE 4/4 and 2/4 genotypes as well as allele 4 were linked with the reduced risk of LDHIV (P=0.0006, OR=0.21; P=0.01, OR=0.18; P=0.0002, OR=0.40). When compared to patients without HIVLD from healthy controls, the APOE 4/4 genotype, 2 and 4 alleles, were linked to a reduced risk of developing HIVLD (P=0.0009, OR=0.14; P=0.0001, OR=0.17; P=0.00001, OR=0.39). When comparing impaired to normal cholesterol levels in patients without HIVLD, the APOE 3/4 genotype was linked with the increased risk of impaired cholesterol levels (P=0.02, OR=3.37). When comparing impaired and normal glucose levels in patients without HIVLD, the APOE 4/4 genotype was associated to an elevated risk of impaired glucose levels (P=0.03, OR=8.27). In multivariate analysis, independent impaired cholesterol, LDL, and glucose levels were associated with a higher risk of lipodystrophy severity (P=0.04, OR=2.33; P=0.001, OR=4.05; P=0.05, OR=2.63). APOE expression was up-regulated in LDHIV with a fold change value of 4.02 compared to those without HIVLD. APOE protein level was found to be higher in patients of the HIVLD group (3.01 mg/dL) compared to those without HIVLD group (2.83 mg/dL). In conclusion, individuals with APOE allele 2 were at higher risk for HIV-1 acquisition and severity of HIVLD, whereas those with APOE allele 4 were at reduced HIVLD severity and development risk. It's possible that APOE's increased level and itsoverexpression are related to the APOE allele 2 in HIVLD patients. The development of LDHIV may be facilitated by the APOE ¾ and 4/4 genotypes as well as abnormalglucose and cholesterol levels.

HMGCR Inhibitor Restores Mitochondrial Dynamics by Regulating Signaling Cascades in a Rodent Alzheimer's Disease Model.

Atorvastatin an HMGCR inhibitor may play a role in enhancing spatial and long-term memory and combating anxious behavior deficits induced by Aß1-42. Behavioral deficit studies, immunoblotting for the antioxidant/apoptotic protein expression, flow cytometry (FACS) for mitochondrial ROS, membrane potential (▲ψm), and histopathological alterations were performed against Aß1-42 toxicity. Aß1-42 was infused directly into the brain through i.c.v for the establishment of the AD model. Atorvastatin (ATOR) was administered orally and was used to treat AD in adult male Wistar rats aged between 200 and 250 g. We confirmed that ATOR administration significantly attenuates the Aß1-42-induced cognitive decline targeted mitochondrial-mediated age-dependent disease progression. Nrf2 stabilizes to interact SOD2 antioxidant enzyme, allowing transcriptional activity by the steep increase in ▲ψm and a reduction in ROS by activating mitochondrial superoxide scavenger and Nrf2-dependent pathway. These findings confirmed that ATOR has the potential efficacy to modulate the interference in cognitive decline induced by Aß1-42.

Biological Effects of Green Synthesized Al-ZnO Nanoparticles Using Leaf Extract from Anisomeles indica (L.) Kuntze on Living Organisms.

The synthesis of Al-ZnO nanoparticles (NPs) was achieved using a green synthesis approach, utilizing leaf extract from Anisomeles indica (L.) in a straightforward co-precipitation method. The goal of this study was to investigate the production of Al-ZnO nanoparticles through the reduction and capping method utilizing Anisomeles indica (L.) leaf extract. The powder X-ray diffraction, UV spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy with EDAX analysis were used to analyze the nanoparticles. X-ray diffraction analysis confirmed the presence of spherical structures with an average grain size of 40 nm in diameter, while UV-visible spectroscopy revealed a prominent absorption peak at 360 nm. FTIR spectra demonstrated the presence of stretching vibrations associated with O-H, N-H, C=C, C-N, and C=O as well as C-Cl groups indicating their involvement in the reduction and stabilization of nanoparticles. SEM image revealed the presence of spongy, spherical, porous agglomerated nanoparticles, confirming the chemical composition of Al-ZnO nanoparticles through the use of the EDAX technique. Al-ZnO nanoparticles showed increased bactericidal activity against both Gram-positive and Gram-negative bacteria. The antioxidant property of the green synthesized Al-ZnO nanoparticles was confirmed by DPPH radical scavenging with an IC50 value of 23.52 indicating excellent antioxidant capability. Green synthesized Al-ZnO nanoparticles were shown in in vivo studies on HeLa cell lines to be effective for cancer treatment. Additionally, α-amylase inhibition assay and α-glucosidase inhibition assay demonstrated their potent anti-diabetic activities. Moving forward, the current methodology suggests that the presence of phenolic groups, flavonoids, and amines in Al-ZnO nanoparticles synthesized with Anisomeles indica (L.) extract exhibit significant promise for eliciting biological responses, including antioxidant and anti-diabetic effects, in the realms of biomedical and pharmaceutical applications.

Innovative disposable in-tip cellulose paper (DICP) device for facile determination of pesticides in postmortem blood samples: A proof-of-concept study.

Accurately identifying and quantifying toxicants is crucial for medico-legal investigations in forensic toxicology; however, low analyte concentrations and the complex samples matrix make this work difficult. Therefore, a simplified sample preparation procedure is crucial to streamline the analysis to minimize sample handling errors, reduce cost and improve the overall efficiency of analysis of toxicants. To address these challenges, an innovative disposable in-tip cellulose paper (DICP) device has been developed for the extraction of three pesticides viz. Chlorpyrifos, Quinalphos and Carbofuran from postmortem blood samples. The DICP device leverages cellulose paper strips housed within a pipette tip to streamline the extraction process, significantly reducing solvent usage, time, and labor while maintaining high analytical accuracy. The extraction of pesticides from postmortem blood using the DICP device involves a streamlined process characterized by adsorption and desorption. The diluted blood samples were processed through the DICP device via repeated aspirating and dispensing calyces to adsorb the pesticides onto the cellulose paper. The adsorbed pesticides are then eluted using acetone, which is collected for GC-MS analysis. The method was meticulously optimized, achieving a limit of quantification in the range of 0.009-0.01 µg mL-1. The intra-day and inter-day precisions were consistently less than 5 % and 10 %, respectively, with accuracy ranging from 94-106 %. Relative recoveries for the analytes were observed to be between 60 % and 93.3 %, and matrix effects were determined to be less than 10 %. The method's sustainability was validated with a whiteness score of 98.8, an AGREE score of 0.64, a BAGI score of 70 and ComplexMoGAPI score of 77. Applicability was demonstrated through successful analysis of real postmortem blood samples and proficiency testing samples, highlighting its potential utility in forensic toxicology.

Ceftriaxone and MC-100093 mitigate fentanyl-induced cardiac injury in mice: Preclinical investigation of its underlying molecular mechanisms.

Drug addiction is considered a worldwide concern and one of the most prevailing causes of death globally. Opioids are highly addictive drugs, and one of the most common opioids that is frequently used clinically is fentanyl. The potential harmful effects of chronic exposure to opioids on the heart are still to be elucidated. Although ß-lactam antibiotics are well recognized for their ability to fight bacteria, its protective effect in the brain and liver has been reported. In this study, we hypothesize that ß-lactam antibiotic, ceftriaxone, and the novel synthetic non-antibiotic ß-lactam, MC-100093, are cardioprotective against fentanyl induced-cardiac injury by upregulating xCT expression. Mice were exposed to repeated low dose (0.05 mg/kg, i.p.) of fentanyl for one week and then challenged on day 9 with higher dose of fentanyl (1 mg/kg, i.p.). This study investigated cardiac histopathology and target genes and proteins in serum and cardiac tissues in mice exposed to fentanyl overdose and ß-lactams. We revealed that fentanyl treatment induced cardiac damage as evidenced by elevated cardiac enzymes (troponin I). Furthermore, fentanyl treatment caused large aggregations of inflammatory cells and elevation in the areas and volumes of myocardial fibers, indicating hypertrophy and severe cardiac damage. Ceftriaxone and MC-100093 treatment, However, induced cardioprotective effects as evidenced by marked reduction in cardiac enzymes (troponin I) and changes in histopathology. Furthermore, ceftriaxone and MC-100093 treatment decreased the levels of hypertrophic genes (α-MHC & ß-MHC), apoptotic (caspase-3), and inflammatory markers (IL-6 & NF-κB). This study reports for the first time the cardioprotective effect of ß-lactams against fentanyl-induced cardiac injury. Further studies are greatly encouraged to completely identify the cardioprotective properties of ceftriaxone and MC-100093.

Neuroinflammation and Neurometabolomic Profiling in Fentanyl Overdose Mouse Model Treated with Novel ß-Lactam, MC-100093, and Ceftriaxone.

Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and ß-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using ß-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography-mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the ß-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that ß-lactams may be promising drugs for treating fentanyl use disorder.

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approach is biomaterial-assisted biotherapy, which takes advantage of biomaterials' special capabilities, such as high biocompatibility and bioactive characteristics. When administered via different routes, drug molecules deal with biological barriers; DDSs help them overcome these hurdles. With their adaptable features and ample packing capacity, biomaterial-based delivery systems allow for the targeted, localised, and prolonged release of medications. Additionally, they are being investigated more and more for the purpose of controlling the interface between the host tissue and implanted biomedical materials. This review discusses innovative nanoparticle designs for precision and non-personalised applications to improve precision therapies. We prioritised nanoparticle design trends that address heterogeneous delivery barriers, because we believe intelligent nanoparticle design can improve patient outcomes by enabling precision designs and improving general delivery efficacy. We additionally reviewed the most recent literature on biomaterials used in biotherapy and vaccine development, covering drug delivery, stem cell therapy, gene therapy, and other similar fields; we have also addressed the difficulties and future potential of biomaterial-assisted biotherapies.

Green composites for sustainable food packaging: Exploring the influence of lignin-TiO2 nanoparticles on poly(butylene adipate-co-terephthalate).

Titanium dioxide (TiO2) is a common pigment used in food packaging to provide a transparent appearance to plastic packaging materials. In the present study, poly(butylene adipate-co-terephthalate) (PBAT) incorporated with lignin-TiO2 nanoparticles (L-TiO2) eco-friendly composite films was prepared by employing an inexpensive melting and hot-pressing technique. The P-L-TiO2 composite films have been studied using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), Thermogravimetric analysis (TGA), and Differential scanning calorimetry (DSC) analysis. The FTIR results and homogeneous, dense SEM images confirm the interaction of L-TiO2 with the PBAT matrix. It has also been found that the addition of L-TiO2 nanoparticles can increase the crystallinity, tensile strength, and thermal stability of PBAT. The addition of L-TiO2 increased the tensile strength and decreased the elongation at break of films. The maximum tensile strength of the film, achieved with 5 wt% L-TiO2, was 47.0 MPa, compared with 24.3 MPa for pure PBAT film. The composite film with 5 wt% L-TiO2 has outstanding oxygen and water vapor barrier properties. As the content of lignin-TiO2 increases, the antimicrobial activity of the composite films also increases; the percentage of growth of all the tested bacteria Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) is significantly reduced. Strawberries were packed to evaluate the suitability of produced composite films as packaging materials, as they effectively preserved pigments from accumulation and extended the shelf-life as compared to commercial polyethylene packaging film.

Sinapic acid-pullulan based inflammation responsive nanomicelles for the local treatment of experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introduced Rebamipide (Reb)-loaded Sinapic acid (SA)-Pullulan (PL) nanomicelles (Reb@SA-PL NMs), a nanotechnology based drug delivery system for the treatment of inflammatory arthritis. PL is a polysaccharide obtained from the fungus Aureobasidium pullulans, and SA is a bioactive polyphenol found in various plants. Both are classified by US-FDA Generally Recognised as Safe (GRAS) materials. Reb@SA-PL NMs found to be cytocompatible. Subsequently, intra-articular administration of Reb@SA-PL NMs enhances the anti-arthritic potential compared to free Reb drug in collagen-induced experimental inflammatory arthritis rat model. Reb@SA-PL NMs reduced the expression of RANKL receptor and Nf-κB. Reb@SA-PL NMs reverses the breakdown of type II collagen, MMP-13, and inhibits the pro-inflammatory markers. Reb@SA-PL NMs prevented bone erosion, cartilage degradation, joint oedema, and synovial inflammation. The results of the study demonstrated that Reb@SA-PL NMs, an enzyme-responsive drug delivery system, has excellent potential for alleviating inflammatory arthritis by blocking MMP-13 and RANKL.

The C-terminus of Rad is required for membrane localization and L-type calcium channel regulation.

L-type CaV1.2 current (ICa,L) links electrical excitation to contraction in cardiac myocytes. ICa,L is tightly regulated to control cardiac output. Rad is a Ras-related, monomeric protein that binds to L-type calcium channel ß subunits (CaVß) to promote inhibition of ICa,L. In addition to CaVß interaction conferred by the Rad core motif, the highly conserved Rad C-terminus can direct membrane association in vitro and inhibition of ICa,L in immortalized cell lines. In this work, we test the hypothesis that in cardiomyocytes the polybasic C-terminus of Rad confers t-tubular localization, and that membrane targeting is required for Rad-dependent ICa,L regulation. We introduced a 3xFlag epitope to the N-terminus of the endogenous mouse Rrad gene to facilitate analysis of subcellular localization. Full-length 3xFlag-Rad (Flag-Rad) mice were compared with a second transgenic mouse model, in which the extended polybasic C-termini of 3xFlag-Rad was truncated at alanine 277 (Flag-RadΔCT). Ventricular cardiomyocytes were isolated for anti-Flag-Rad immunocytochemistry and ex vivo electrophysiology. Full-length Flag-Rad showed a repeating t-tubular pattern whereas Flag-RadΔCT failed to display membrane association. ICa,L in Flag-RadΔCT cardiomyocytes showed a hyperpolarized activation midpoint and an increase in maximal conductance. Additionally, current decay was faster in Flag-RadΔCT cells. Myocardial ICa,L in a Rad C-terminal deletion model phenocopies ICa,L modulated in response to ß-AR stimulation. Mechanistically, the polybasic Rad C-terminus confers CaV1.2 regulation via membrane association. Interfering with Rad membrane association constitutes a specific target for boosting heart function as a treatment for heart failure with reduced ejection fraction.

Exploration of Calocybe indica mushroom phenolic acid-kidney bean protein complex: Functional properties, amino acid profiles, in-vitro digestibility, and application in vegan product development.

The study evaluates the interaction between Calocybe indica mushroom polyphenols (phenolic acid) and kidney bean protein (KBPM), aiming to enhance vegan food quality. The mushrooms exhibited a carbohydrate content of 3.65%, an antioxidant activity of 55.04 ± 0.17%, and a phenolic content of 4.86 mg GAE/g. Caffeic and cinnamic acids were identified through high-pressure liquid chromatography. Various concentrations of KBPM were tested at phenolic acid concentrations of 0.025, 0.050, 0.1, 0.2, 0.4, 0.8, and 1%, among these, KBPM 0.2 demonstrated the highest binding efficiency of 99.40 ± 0.05%. Notably, this complex improved the protein's functional properties, such as solubility by 11.43%, water and oil holding capacities by 10.62% and 22.04%, and emulsion capacity and stability by 3.69% and 5.83%, respectively, compared to the native protein. The protein-phenolic acid complex also enhanced thermal stability, surface charge, amino acid content, and reduced particle size compared to native protein. These enhancements also improved protein digestibility and sensory attributes in a fruit-based smoothie.

Extraction, characterization, and utilization of mung bean starch as an edible coating material for papaya fruit shelf-life enhancement.

This research was aimed to investigate the utilization of mung bean starch as an innovative edible coating material to enhance the shelf-life of cut papaya fruits. The study focused on the extraction process of mung bean starch and its subsequent characterization through various analyses. Particle size (142.3 ± 1.24 nm), zeta potential (-25.52 ± 1.02 mV), morphological images, Fourier transform infrared (FTIR) spectra, and thermal stability (68.36 ± 0.15°C) were assessed to determine the mung bean starch properties. The functional properties, such as bulk density (0.51 ± 0.004 g/cm3) and tapped density (0.62 ± 0.010 g/cm3), angle of repose (21.61°), swelling power (12.26 ± 0.25%), and minimum gelation concentration (4.01 ± 1.25%), were examined to detect its potential as a coating base material. Subsequently, the prepared mung bean starch coating solution (1%, 2%, 3%, 4%, and 5%) was applied to papaya fruits and the coated fruits' physicochemical characteristics evaluated during storage. These characteristics encompassed color, weight loss, pH shifts, total soluble solids, titratable acidity, vitamin C content, fruit firmness, microbial analysis, and sensory attributes. The results revealed that starch coating on papaya maintained its color, reduced weight loss, preserved vitamin C, and delayed firmness loss, enhancing shelf-life when compared to control sample. These findings demonstrated the effectiveness of mung bean starch coatings in preserving papaya fruits. The research made a significant contribution to the use of mung bean starch as a potential coating material for improving the shelf-life of papaya fruits. This finding has great promise for the field of food preservation and quality control.

A review of valorization of agricultural waste for the synthesis of cellulose membranes: Separation of organic, inorganic, and microbial pollutants.

Agricultural waste presents a significant environmental challenge due to improper disposal and management practices, contributing to soil degradation, biodiversity loss, and pollution of water and air resources. To address these issues, there is a growing emphasis on the valorization of agricultural waste. Cellulose, a major component of agricultural waste, offers promising opportunities for resource utilization due to its unique properties, including biodegradability, biocompatibility, and renewability. Thus, this review explored various types of agricultural waste, their chemical composition, and pretreatment methods for cellulose extraction. It also highlights the significance of rice straw, sugarcane bagasse, and other agricultural residues as cellulose-rich resources. Among the various membrane fabrication techniques, phase inversion is highly effective for creating porous membranes with controlled thickness and uniformity, while electrospinning produces nanofibrous membranes with high surface area and exceptional mechanical properties. The review further explores the separation of pollutants including using cellulose membranes, demonstrating their potential in environmental remediation. Hence, by valorizing agricultural residues into functional materials, this approach addresses the challenge of agricultural waste management and contributes to the development of innovative solutions for pollution control and water treatment.

An approach to manufacturing well-being milk chocolate in partial replacement of lecithin by the functional plant-based combination.

Lecithin is constituted of a glycerophospholipid mixture and is abundantly used as an emulsifying agent in various food applications including chocolate production. However, overconsumption of lecithin may create an adverse effect on human health. Thus, this study aims to replace the lecithin with plant-based gums. Different ratios of guar and arabic gum (25%-75%) and their blend (25%-75%) were employed as partial replacement of lecithin. Milk chocolate prepared using 40% guar gum (60GGL [guar gum, lecithin]), 25% arabic gum (75AGL [arabic gum, lecithin]), and a blend of 15 arabic gum and 10 guar gum (65AGGL [arabic gum, guar gum, lecithin]) showed similar rheological behavior as compared to control chocolate (100% lecithin). The fat content of 65AGGL (37.85%) was significantly lower than that of the control sample (43.37%). Rheological behavior exhibited shear-thinning behavior and samples (60GGL-75GGL-80GGL, 65AGL-75AGL, and 65AGGL-75AGGL) showed similar rheological properties as compared to control. The chocolate samples (60GGL and 65AGGL) showed significantly (p < .05) higher hardness values (86.01 and 83.55 N) than the control (79.95 N). As well, gum-added chocolates exhibited higher thermal stability up to 660°C as compared to the control sample. The Fourier transform infrared spectroscopy (FTIR) analysis revealed predominant ß-(1 → 4) and ß-(1 → 6) glycosidic linkages of the gums and lecithin. Sensory evaluation revealed a comparable score of gum-added milk chocolate in comparison to control samples in terms of taste, texture, color, and overall acceptance. Thus, plant exudate gums could be an excellent alternative to lecithin in milk chocolate, which can enhance the textural properties and shelf life.

Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-ß) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-ß mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

The link between Alzheimer's disease and stroke: A detrimental synergism.

Being age-related disorders, both Alzheimer's disease (AD) and stroke share multiple risk factors, such as hypertension, smoking, diabetes, and apolipoprotein E (APOE) Ɛ4 genotype, and coexist in patients. Accumulation of amyloid-ß plaques and neurofibrillary tangled impair cognitive potential, leading to AD. Blocked blood flow in the neuronal tissues, causes neurodegeneration and cell death in stroke. AD is commonly characterized by cerebral amyloid angiopathy, which significantly elevates the risk of hemorrhagic stroke. Patients with AD and stroke have been both reported to exhibit greater cognitive impairment, followed by multiple pathophysiological mechanisms shared between the two. The manuscript aims to elucidate the relationship between AD and stroke, as well as the common pathways and risk factors while understanding the preventive therapies that might limit the negative impacts of this correlation, with diagnostic modalities and current AD treatments. The authors provide a comprehensive review of the link and aid the healthcare professionals to identify suitable targets and risk factors, that may retard cognitive decline and neurodegeneration in patients. However, more intricate research is required in this regard and an interdisciplinary approach that would target both the vascular and neurodegenerative factors would improve the quality of life in AD patients.

Development of ternary polymeric film based on modified mango seed kernel starch, carboxymethyl cellulose, and gum acacia to extend the shelf-life of bun-bread.

Non-conventional starch sources have attracted substantial attention due to their preferred physicochemical and mechanical properties similar to conventional sources. This study aimed to enhance the mechanical properties of mango seed kernel starch (MSKS) based films reinforced with carboxymethyl cellulose (CMC) and gum acacia (GA). Physical modification of MSKS was carried out using microwave-assisted at 180 W for 1 min. SEM results confirmed the oval and irregular shape of starch. The particle size of native starch (NS) (754.9 ± 20.4 nm) was higher compared to modified starch (MS) 336.6 ± 88.9 nm with a surface charge of -24.80 ± 3.92 to -34.87 ± 3.92 mV, respectively. Several functional groups including hydroxyl (OH) and carboxyl (CH) were confirmed in NS and MS. Different ratios of the MS, NS, CMC, and GA were used for the fabrication of films. Results revealed the higher tensile strength of M/C/G-1 (57.45 ± 0.05 nm) and M/C/G-2 (50.77 ± 0.58), compared to control C-4 (100 % native starch) (4.82 ± 0.04) respectively. The ternary complex provided excellent permeability against moisture and the film with a higher starch concentration confirmed the uniform thickness (0.09-0.10 mm). Furthermore, selected films (M/C/G-1 and M/C/G-2) reduced the microbial growth and weight loss of the bun compared to the control (C-4) film. Thus, the ternary complex maintained the freshness of the bun-bread for 14 days. It can be potentially used as a cost-effective and eco-friendly packaging material for food applications.

Role of diosmin in preventing doxorubicin-induced cardiac oxidative stress, inflammation, and hypertrophy: A mechanistic approach.

Chemotherapeutic drugs, such as doxorubicin (Dox), are commonly used to treat a variety of malignancies. However, Dox-induced cardiotoxicity limits the drug's clinical applications. Hence, this study intended to investigate whether diosmin could prevent or limit Dox-induced cardiotoxicity in an animal setting. Thirty-two rats were separated into four distinct groups of controls, those treated with Dox (20 mg/kg, intraperitoneal, i.p.), those treated with diosmin 100 mg plus Dox, and those treated with diosmin 200 mg plus Dox. At the end of the experiment, rats were anesthetized and sacrificed and their blood and hearts were collected. Cardiac toxicity markers were analyzed in the blood, and the heart tissue was analyzed by the biochemical assays MDA, GSH, and CAT, western blot analysis (NF-kB, IL-6, TLR-4, TNF-α, iNOS, and COX-2), and gene expression analysis (ß-MHC, BNP). Formalin-fixed tissue was used for histopathological studies. We demonstrated that a Dox insult resulted in increased oxidative stress, inflammation, and hypertrophy as shown by increased MDA levels and reduced GSH content and CAT activity. Furthermore, Dox treatment induced cardiac hypertrophy and damage, as evidenced by the biochemical analysis, ELISA, western blot analysis, and gene expression analysis. However, co-administration of diosmin at both doses, 100 mg and 200 mg, mitigated these alterations. Data derived from the current research revealed that the cardioprotective effect of diosmin was likely due to its ability to mitigate oxidative stress and inflammation. However, further study is required to investigate the protective effects of diosmin against Dox-induced cardiotoxicity.

A chlorogenic acid-conjugated nanomicelle attenuates disease severity in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.