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Nonalcoholic fatty liver disease (NAFLD) is a condition that affects about 24% of people worldwide. Increased liver fat, inflammation, and, in the most severe cases, cell death are all characteristics of NAFLD. However, NAFLD pathogenesis and therapy are still not clear enough. Thus, this study aimed to determine the effect of a high-cholesterol diet (HCD) inducing NAFLD on lipolytic gene expression, liver function, lipid profile, and antioxidant enzymes in rabbits and the modulatory effects of probiotic Lactobacillus acidophilus (L. acidophilus) on it. A total of 45 male New Zealand white rabbits, eight weeks old, were randomly divided into three groups of three replicates (5 rabbits/replicate). Rabbits in group I were given a basal diet; rabbits in group II were given a high-cholesterol diet that caused NAFLD; and rabbits in group III were given a high-cholesterol diet as well as probiotics in water for 8 weeks. The results showed that a high-cholesterol diet caused hepatic vacuolation and upregulated the genes for lipoprotein lipase (LPL), hepatic lipase (HL), and cholesteryl ester transfer protein (CETP). Downregulated low-density lipoprotein receptor (LDLr) gene, increased liver enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)], cholesterol, triglycerides (TG), low-density lipoprotein (LDL), glucose, and total bilirubin. On the other hand, it decreased high-density lipoprotein (HDL), total protein, albumin, and liver antioxidants [glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD)]. Supplementing with probiotics helped to return all parameters to normal levels. In conclusion, probiotic supplementation, especially L. acidophilus, protected against NAFLD, and restored lipolytic gene expression, liver functions, and antioxidants to normal levels. [ABSTRACT FROM AUTHOR]

• In silico screening of 35 phytochemicals from Newbouldia laevis against hexokinase 2. • Insight using molecular docking in terms of binding affinities and interacting residues for predicting molecular mechanism. • Assessing the potency of the lead phytochemicals using molecular dynamic simulations and MMPBSA. • Best drug candidates as hexokinase 2 inhibitors were predicted for further pre-clinical and clinical trials. Newbouldia laevis, also known as the African Border Tree or Fever Tree, is a deciduous tree native to West Africa. The plant is valued for its medicinal properties and is used in traditional medicine for its antimicrobial and anti-inflammatory effects. N. laevis, is a storage tank of phytochemicals with huge health benefits and performances globally for the treatment and management of numerous disease conditions. Limited research exists on the usage of N. laevis for hepatocellular carcinoma (HCC) treatment. This study aims to explore the inhibitory activities of phytochemicals from N. laevis against the hexokinase 2 protein, a target in hepatocarcinoma (HCC) treatment. This study presents a unique in silico approach that includes ligand binding site prediction, molecular docking, molecular dynamics simulation, and Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) methods. A total of 35 phytochemicals with available 3D structures were identified through literature mining. The literature review highlighted the significance of hexokinase 2 protein as a target inhibitor in the treatment of hepatocellular carcinoma (HCC). Molecular docking experiment with the all the identified phytochemicals and hexokinase 2 revealed that all the identified phytochemicals had potential inhibitory activities against the target protein. Moreover, chrysarobin, apigenin and ursolic acid were the best inhibitors with lowest binding energy of −8.9 kcal/mol, −8.7 kcal/mol, and −8.5 kcal/mol, respectively. The docking experiment was validated by comparing the binding affinities with known reference drug Cabozantinib-S-malate (−8.3 kcal/mol). Further, molecular dynamics studies of complexes with the best docking scores and reference drug complexes were described in detail here. The results of 100 ns modeling (RMSD, RMSF, Rg and SASA) show extraordinary stability during the establishment of complexes with apigenin and ursolic acid, as well as favorable binding energy, which was determined theoretically by means of the MM/PBSA method, thereby increase the probability of their acting as promising and likely hexokinase 2 inhibitors. Therefore, the study predicted that apigenin and ursolic acid could be used as a potential inhibitor/antagonist for the hexokinase 2 enzyme. [ABSTRACT FROM AUTHOR]

Phytase is crucial in enhancing the bioavailability and release of phosphorus and other nutrients bound to phytic acid, making them more bioavailable for animal absorption. This study was carried out to inspect the effect of supplementing low phosphorus (P) diet with di‐calcium phosphate (DCP) and liquid phytase enzyme (LP), which contains 1500 FTU/kg, on growth performance, intestinal morphometry, proximate body chemical composition, blood profile, immunity status, liver mitochondrial enzyme activities, the expression response and economic returns of Nile tilapia (Oreochromis niloticus). Three triplicate groups of fish (initial weight 5.405 ± 0.045 g, N = 90) were fed on three different diets for 90 days. The first was a control diet with zero DCP; the second was a control diet supplemented with 0.71% DCP; the third was a control diet supplemented with 0.03% LP. The groups were designated as CG, DCP and LP, respectively. Results showed that LP induced considerable improvements (p < 0.05) in FBW, body weight gain, weight gain rate, specific growth rate, HIS, viscero‐somatic index, spleen‐somatic index, feed conversion ratio, blood parameters and the histomorphometry assessment of intestinal villi absorptive capacity, compared with the other groups. Also, whole‐body protein and lipid contents pointedly (p < 0.05) increased by LP, compared with the DCP group. A positive response (p < 0.05) to the phytase enzyme was noted in complexes I, III and IV of the mitochondrial liver complex enzyme activity. Likewise, the relative gene expression levels of (GHr‐1, IGF‐1, FAS and LPL) were notably (p < 0.05) upregulated by phytase enzyme, associated with DCP and control groups. Further, phytase recorded the highest total return and profit percentage. It can be concluded that Nile tilapia benefits from using phytase enzyme 1500 FTU/kg at 0.03% without adding DCP in terms of good performance and profits. [ABSTRACT FROM AUTHOR]

Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole's well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy. [ABSTRACT FROM AUTHOR]

Background. Human life quality and expectancy have increased dramatically over the past 5 decades because of improvements in nutrition and antibiotic's usage fighting against infectious diseases. Yet, it was soon revealed that the microbes adapted to develop resistance to any of the drugs that were used. Recently, there is great concern that commensal bacteria from food and the gastrointestinal tract of humans and animals could act as a reservoir for antibiotic resistance genes. Methodology. This study was intended for evaluating the phenotypic antibiotic resistance/sensitivity profiles of probiotic bacteria from human breast milk and evaluating the inhibitory effect of the probiotic bacteria against both Gram-negative and Gram-positive bacteria. Results. The results point out that some of the isolated bacteria were resistant to diverse antibiotics including gentamycin, imipenem, trimethoprim sulfamethoxazole, and nalidixic acid. Susceptibility profile to certain antibiotics like vancomycin, tetracycline, ofloxacin, chloramphenicol, streptomycin, rifampicin, and bacitracin was also observed. The antimicrobial qualities of cell-free supernatants of some probiotic bacteria inhibited the growth of indicator bacteria. Also, antimicrobial properties of the probiotic bacteria from the present study attributed to the production of organic acid, bacterial adhesion to hydrocarbons (BATH), salt aggregation, coaggregation with pathogens, and bacteriocin production. Some isolated bacteria from human milk displayed higher hydrophobicity in addition to intrinsic probiotic properties like Gram-positive classification, catalase-negative activity, resistance to gastric juice (pH 2), and bile salt (0.3%) concentration. Conclusion. This study has added to the data of the antibiotic and antimicrobial activity of some probiotic bacteria from some samples of Pakistani women breast milk. Probiotic bacteria are usually considered to decrease gastrointestinal tract diseases by adhering to the gut epithelial and reducing population of pathogens and in the case of Streptococcus lactarius MB622 and Streptococcus salivarius MB620 in terms of hydrophobicity and exclusion of indicator pathogenic strains. [ABSTRACT FROM AUTHOR]

Microcystin-leucine-arginine (MCLR) is the most abundant cyanotoxin produced by cyanobacteria. It induces potent cytotoxicity through oxidative stress and DNA damage. Thymoquinone (TQ) is a natural nutraceutical antioxidant derived from black cumin (Nigella sativa). Physical exercise (EX) improves whole-body metabolic homeostasis. Therefore, this study examined the protective role of swimming exercise and TQ against MC-induced toxicity in mice. Fifty-six healthy adult male albino mice (25–30 g) were randomized into seven groups; group (I) was the negative control and received oral physiological saline for 21 days; group (II) received water EX for 30 min daily; group (III) was intraperitoneally injected with TQ (5 mg/kg daily, for 21 days); group (IV) was intraperitoneally administered MC (10 μg/kg daily, for 14 days) and acted as the positive toxic control; group (V) was treated with MC and water EX; group (VI) was injected with MC and TQ; finally, group (VII) was treated with MC with TQ and water EX. In comparison with the control group, the results showed hepatic, renal, and cardiac toxicity in the MCLR-treated group, indicated by a significant increase (p < 0.05) in serum levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transferase (ALT), cholesterol, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-myocardial band (CK-MB), urea, creatinine, interleukin-6, interleukin -1β, and tumor necrosis factor-α levels. In addition, there were significant elevations (p < 0.05) in malondialdehyde (MDA) and nitric oxide (NO) levels and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in hepatic, cardiac, and renal tissues. Treatment with either TQ or water EX significantly improved (p < 0.05) the MC-induced toxicity with superiority of the TQ group in the restoration of normal ranges; however, cotreatment with both TQ and swimming EX showed the most improvement and restoration to normal ranges as a result of increasing EX clinical efficacy by TQ. [ABSTRACT FROM AUTHOR]

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1–MCu9) and Zn II (MZn1–MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development. [ABSTRACT FROM AUTHOR]

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 ± 1.13), while a maximum of 92.87 ± 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 µm. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t½) of 4.54 ± 0.18 h and a Cmax of 128 ± 0.87 (ng/mL); Tmax was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a chronic inflammatory disorder in the intestinal tract as a response to the use of gluten in genetically predisposed individuals. It is a worldwide problem, with a high prevalence rate in North America. This is a descriptive cross-sectional study involving 1090 samples collected from different hospitals of Rawalpindi and Islamabad, Pakistan, from January 2019 to December 2019. In this study, 1090 blood samples screened for seroprevalence of anti-tTG antibodies in CD symptomatic patients via ELISA (enzyme-linked immunosorbent assay). 1090 fecal samples from the same CD patients were collected and tested for the presence of rotavirus (RV) via ELISA and RT-PCR. Of the 1090 patients tested for seroprevalence of anti-tTG antibodies, 112/1090 (10.3%) were found to be positive. Of the 112 anti-tTG-positive patients, 78/112 (70%) were positive for RV via ELISA and 74/112 (66.1%) were RV positive via RT-PCR. A statistically significant association was reported between rotavirus infection and celiac disease (p ˂ 0.05). Anti-tTG antibodies were higher in age group 6 (12-18 years) patients (18.4%) and at minimum in age group 3 (1-3 years) patients (4.8%). However, there was a statistically insignificant relationship between group age and CD prevalence (p > 0.05). The highest CD prevalence was noted during winter season (19.6%) and the lowest (3.0%) during fall/autumn. Our study findings demonstrate that Pakistan has a high prevalence of CD compared to other studies. Further studies in the fields of environmental risk factors and treatment with more advanced serological and histopathological studies are needed in the future. [ABSTRACT FROM AUTHOR]

This research was designed to identify thermodynamically and kinetically stable lipidic self-emulsifying formulations through simple energy dynamics in addition to highlighting and clarifying common ambiguities in the literature in this regard. Proposing a model study, this research shows how most of the professed energetically stable systems are actually energetically unstable, subjected to indiscriminate and false characterization, leading to significant effects for their pharmaceutical applications. A self-emulsifying drug delivery system (SEDDS) was developed and then solidified (S-SEDDS) using a model drug finasteride. Physical nature of SEDDS was identified by measuring simple dynamics which showed that the developed dispersion was thermodynamically unstable. An in vivo study of albino rats showed a three-fold enhanced bioavailability of model drug with SEDDS as compared to the commercial tablets. The study concluded that measuring simple energy dynamics through inherent properties can distinguish between thermodynamically stable and unstable lipidic systems. It might lead to correct identification of a specific lipidic formulation and the application of appropriate characterization techniques accordingly. Future research strategies include improving their pharmaceutical applications and understanding the basic differences in their natures. [ABSTRACT FROM AUTHOR]

Tridax procumbens (TP) is a traditional Indian therapeutic plant and was evaluated for its blood glucose lowering abilities, as well as for its ability to curb diabetic neuropathy (DN). Administrating 45 mg/kg body weight of streptozotocin (STZ) intraperitoneally for four weeks, DN was induced in Wistar rats. After the rats' tails were clipped, the blood glucose levels were measured. Body weight and urine volume were also assessed. Oxidative stress makers such as superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), catalase (CAT), inflammatory cytokines for instance tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were estimated. Further, protein kinase C (PKC-β) and vascular endothelial growth factor (VEGF) were also estimated as angiogenic markers. Behavioral parameters were also evaluated by using cold allodynia using acetone test, hot allodynia using Eddy's hot plate, grip strength test using Rota rod, and hyperalgesia test using Tail flick technique. The statistical assessment of findings was done employing one-way (ANOVA) analysis of variance, and subsequently Turkey as post hoc with GraphPad Prism software package. The ingestion of TP for 1 month in DN rats stemmed in a substantial decline in blood glucose concentrations matched to nontreated rats with DN. There had been a considerable improvement in DN as evident from the finding from biochemical markers. The serum level of antioxidant defense enzymes was significantly increased, while the activities of TBARS had been substantially reduced in the TP treated rats with DN. TP averted DN-triggered surge levels of TNF-α and IL-6 in the serum. Further, PKC-β and VEGF concentrations had been also reduced by the treatment TP. The findings of this research demonstrated that the restorative impact of TP on DN rats might be linked to the anti-inflammatory and antioxidative antiangiogenic retorts. [ABSTRACT FROM AUTHOR]

The current study sought to synthesize silver nanoparticles (AgNPs) from Amaryllis vittata (L.) leaf and bulb extracts in order to determine their biological significance and use the toxic plants for human health benefits. The formation of silver nanoparticles was detected by a change in color from whitish to brown for bulb-AgNPs and from light green to dark brown for leaf-AgNPs. For the optimization of silver nanoparticles, various experimental physicochemical parameters such as pH, temperature, and salt were determined. UV-vis spectroscopy, Fourier transform infrared spectroscopy, X-ray dispersion spectroscopy, scanning electron microscopy, and energy dispersion spectroscopy analysis were used to characterize nanoparticles. Despite the fact that flavonoids in plant extracts were implicated in the reduction and capping procedure, the prepared nanoparticles demonstrated maximum absorbency between 400 and 500 nm. SEM analysis confirmed the preparation of monodispersed spherical crystalline particles with fcc structure. The bioinspired nanoparticles were found to show effective insecticidal activity against Tribolium castaneum and phytotoxic activity against Lemna aequincotialis. In comparison to plant extracts alone, the tested fabricated nanoparticles showed significant potential to scavenge free radicals and relieve pain. Antibacterial testing against human pathogenic strains, i.e., Escherichia coli and Pseudomonas aureginosa, and antifungal testing against Aspergillus niger revealed the significant potential for microbe resistance using AgNPs. As a result of the findings, the tested silver nanoparticles demonstrated promising potential for developing new and effective pharmacological and agricultural medications. Furthermore, the effects of biogenic AgNPs on an in vitro culture of Solanum tuberosum L. plants were investigated, and the findings indicated that bulb-AgNPs and leaf-AgNPs produced biomass and induced antioxidants via their active constituents. As a result, bulb-AgNPs and leaf-AgNPs may be recommended for use in Solanum tuberosum L. tissue culture for biomass fabrication and metabolic induction. [ABSTRACT FROM AUTHOR]

Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. Method: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts' anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. Results: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites. [ABSTRACT FROM AUTHOR]

The objective of the current study was to evaluate the phytochemical and pharmacological potential of the Cornus macrophylla. C. macrophylla belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of C. macrophyll were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of C. macrophylla was studied by 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the C. macrophylla were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of C. macrophylla confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC50 values of 09.54 μg/mL and 7.8 μg/mL against ABTS and DPPH assay respectively. Among all the fractions of C. macrophylla, Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC50 values were 93.35 μg/mL against COX-2 and 75.64 μg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of C. macrophylla. C. macrophylla has promising potential as a source for the development of new drugs against inflammation in the future. [ABSTRACT FROM AUTHOR]

Microglial cells serve as molecular sensors of the brain that play a role in physiological and pathological conditions. Under normal physiology, microglia are primarily responsible for regulating central nervous system homeostasis through the phagocytic clearance of redundant protein aggregates, apoptotic cells, damaged neurons, and synapses. Furthermore, microglial cells can promote and mitigate amyloid β phagocytosis and tau phosphorylation. Dysregulation of the microglial programming alters cellular morphology, molecular signaling, and secretory inflammatory molecules that contribute to various neurodegenerative disorders especially Alzheimer's disease (AD). Furthermore, microglia are considered primary sources of inflammatory molecules and can induce or regulate a broad spectrum of cellular responses. Interestingly, in AD, microglia play a double-edged role in disease progression; for instance, the detrimental microglial effects increase in AD while microglial beneficiary mechanisms are jeopardized. Depending on the disease stages, microglial cells are expressed differently, which may open new avenues for AD therapy. However, the disease-related role of microglial cells and their receptors in the AD brain remain unclear. Therefore, this review represents the role of microglial cells and their involvement in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Nanoparticles play a vital role in cancer treatment to deliver or direct the drug to the malignant cell, avoiding the attacking of normal cells. The aim of the study is to formulate folic-acid-modified chitosan nanoparticles for colon cancer. Chitosan was successfully conjugated with folic acid to produce a folic acid–chitosan conjugate. The folate-modified chitosan was loaded with 5-FU using the ionic gelation method. The prepared nanoparticles were characterized for size, zeta potential, surface morphology, drug contents, entrapment efficiency, loading efficiency, and in vitro release study. The cytotoxicity study of the formulated nanoparticles was also investigated. The conjugation of folic acid with chitosan was confirmed by FTIR and NMR spectroscopy. The obtained nanoparticles were monodispersed nanoparticles with a suitable average size and a positive surface charge. The size and zeta potential and PDI of the CS-5FU-NPs were 208 ± 15, 26 ± 2, and +20 ± 2, respectively, and those of the FA-CS-5FU-NPs were 235 ± 12 and +20 ± 2, respectively, which are in the acceptable ranges. The drug contents' % yield and the %EE of folate-decorated NPs were 53 ± 1.8% and 59 ± 2%, respectively. The in vitro release of the FA-CS-5FU-NPs and CS-5FU-NPs was in the range of 10.08 ± 0.45 to 96.57 ± 0.09% and 6 ± 0.31 to 91.44 ± 0.21, respectively. The cytotoxicity of the nanoparticles was enhanced in the presence of folic acid. The presence of folic acid in nanoparticles shows much higher cytotoxicity as compared to simple chitosan nanoparticles. The folate-modified nanoparticles provide a potential way to enhance the targeting of tumor cells. [ABSTRACT FROM AUTHOR]

The apple is the most widely used fruit globally. Apples are more prone to fungal spoilage, which leads to browning and subsequent changes in their flavor and texture. Browning is also caused by the tyrosinase enzyme. By inhibiting tyrosinase initiation and fungal spoilage in fruits, the natural flavor and texture of fruits can be maintained. Biogenic NPs can act as antioxidants to inhibit tyrosinase and due to oxidative stress, it also catalyzes the deformation of fungal hyphae and spores. Nanotechnology is a research hotspot that has gained considerable interest due to its potential inferences in biosciences and food preservation technology. The present study aims to use biomass from the Fagonia cretica to create bio-inspired manganese oxide MnO2 NPs and to evaluate its bio-catalytic potential for antifungal anti-browning through the inhibition of tyrosinase and its antioxidant potential for preserving apple flavor and texture. The green synthesized nanoparticles were extensively analyzed using UV spectroscopy, XRD, SEM, EDX, and FTIR techniques. Moreover, the synthesized manganese oxide nanoparticles (MnO2 NPs) were evaluated for their bio-catalytic potential as anti-fungal and anti-spoiling agents. The values of antifungal activity among all the samples were 14.2 ± 86 mm, 8.9 ± 6.0 mm, 17.7 ± 1.26, and 20.7 ± 4.38 mm for Penicillium expansum, Monilinia fructigena, Penicillium chrysogenum, and Aspergillus oryzae at 200 µg/well, respectively. Moreover, the biogenic NPs were evaluated for their anti-browning potential through the inhibition of tyrosinase. MnO2 NPs have been shown to have considerable inhibitory effects on tyrosinase up to 64.8 ± 0.16 at 200 µg/mL and (27.2 ± 0.58) at 25 µg/mL. Biogenic MnO2 NPs can also act as antioxidants to inhibit tyrosinase and fungal growth by the formation of free radicals that damage the fungal hyphae and, as a result, slow down browning. The maximum DPPH free radical scavenging activity was 74.5 ± 0.39% at 200 µg/mL, and the minimum was 12.4 ± 0.27 at 25 µg/mL. The biogenic MnO2 NPs are biocompatible and play a potent role in maintaining the flavor and texture of apples. [ABSTRACT FROM AUTHOR]

Investigating the impact of early egg production selection (the first 90 d of laying) on egg production features, cumulative selection response (CSR), and the mRNA expression of gonadotropins (FSHβ and LHβ), and their receptors (FSHR and LHR), in Japanese quails was the goal. The selection experiment involved 1293 females in all, 257 from the base group and 1036 from the 4 selected generations. Age and body weight at sexual maturity (ASM, BWSM), weight of the first egg (WFE), days to the first 10 eggs (DF10E), egg mass for the first 10 eggs (EMF10E), egg weight (EW), egg number at the first 90 d of laying (EN90D), and egg mass at the first 90 d of laying (EM90D) were all recorded. Most egg production traits had heritability estimates that were low to moderate and ranged from 0.17 to 0.33., where the highest estimates were reported for EN90D (0.33) and BWSM (0.32). With the exception of EN90D, low to moderate positive genetic correlations were observed between ASM and other egg production traits (0.17–0.44). The fourth generation showed significantly (P < 0.05) lower ASM and DF10E but higher BWSM, WFE, EN90D, EM10E, and EM90D when compared with the base generation. CSR were significant (P < 0.05) for ASM (−6.67 d), BWSM (27.13 g), WFE (0.93 g), DF10E (−1.25 d), EN90D (7.24 egg), EM10E (10.57 g), and EM90D (140.0 g). FSHβ, LHβ, FSHR , and LHR gene mRNA expression was considerably (P < 0.05) greater in the fourth generation compared to the base generation. In conclusion, selection programs depending on the efficiency of egg production (EN90D) could improve the genetic gain of egg production traits and upregulate the mRNA expression of FSHβ, LHβ, FSHR , and LHR genes in selected quails (fourth generation). These findings might help to enhance breeding plans and create commercial lines of high egg production Japanese quails. [ABSTRACT FROM AUTHOR]

Background: Broilers are continuously stressed because of the rapid growth rate and the environmental issues associated with industrialized poultry production systems, which lead to higher susceptibility for infection with pathogens. It is well known that vitamin E (Vit. E) and selenium (Se) supplementation have protective functions in such stressful conditions. This protocol was to investigate the impact of Vit. E and/or Se on the production performance, some serum biochemistry, and expression of some growth-related gene in the liver tissue of the broilers. The day-old chicks were allotted into four groups according to the supplement; Control group and groups supplemented with Vit. E and/or Se into Vit. E group (100 mg Vit. E/kg diet), Se group (0.3 mg sodium selenite/kg diet), and Vit E + Se group that supplemented with both Vit. E and Se. Results: The data of the present experiment showed that dietary inclusion of Vit. E and/or Se significantly (P ≤ 0.05) improved the production parameters without any side effect on the general health status of the broilers, which indicated by normal serum biochemical parameters. Moreover, the treatments positively affected the expression of some genes related to growth performance including growth hormone receptor (GHR) and insulin-like growth factor 1 (IGF1) in the liver tissue of broilers. Conclusion: Dietary supplementation of Vit. E and/or Se improved the production parameters and upregulate the growth-related genes without effect on the general health status of the broilers. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSLysozymes, efficient alternative supplements to antibiotics, have several benefits in poultry production. In the present study, 120, one–day–old, Ross 308 broiler chickens of mixed sex, were allocated into 2 equal groups, lysozyme treated group (LTG) and lysozyme free group (LFG), to evaluate the efficacy of lysozyme (Lysonir®) usage via both drinking water (thrice) and spray (once). LTG had better (p = 0.042) FCR, and higher European production efficiency factor compared to LFG (p = 0.042). The intestinal integrity score of LTG was decreased (p = 0.242) compared to that of LFG; 0.2 vs. 0.7. Higher (p ≤ 0.001) intestinal Lactobacillus counts were detected in chickens of LTG. Decreased (p ≤ 0.001) IL-1β and CXCL8 values were reported in LTG. The cellular immune modulation showed higher (p ≤ 0.001) opsonic activity (MΦ and phagocytic index) in LTG vs. LFG at 25 and 35 days. Also, higher (p ≤ 0.001) local, IgA, and humoral, HI titers, for both Newcastle, and avian influenza H5 viruses were found in LTG compared to LFG. In conclusion, microbial lysozyme could improve feed efficiency, intestinal integrity, Lactobacillus counts, anti-inflammatory, and immune responses in broiler chickens.Exogenous aqueous and spray microbial lysozyme enhanced growth in commercial broiler chickensThe postbiotic effects of microbial lysozyme modulated intestinal integrity.Anti-inflammatory, as well as local, cellular, and humoral immune response were stimulated by lysozyme supplementation.Exogenous aqueous and spray microbial lysozyme enhanced growth in commercial broiler chickensThe postbiotic effects of microbial lysozyme modulated intestinal integrity.Anti-inflammatory, as well as local, cellular, and humoral immune response were stimulated by lysozyme supplementation. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a widely distributed mycotoxin, causing hepatotoxicity and oxidative stress. One of the most famous unicellular cyanobacteria is Spirulina platensis (SP) which is well known for its antioxidant characteristics against many toxicants. Therefore, this study aimed to investigate the antioxidant potential and hepatoprotective ability of SP against oxidative stress and cytotoxicity in male Wistar albino rats intraperitoneally injected with AFB1. Rats were separated into five groups as follows: negative control administered with saline; SP (1000 mg/kg BW) for two weeks; AFB1 (2.5 mg/kg BW) twice on days 12 and 14; AFB1 (twice) + 500 mg SP/kg BW (for two weeks) and AFB1 (twice) + 1000 mg SP/kg BW (for two weeks). Liver and blood samples were assembled for histological and biochemical analyses. AFB1 intoxicated rats showed a marked elevation in serum biochemical parameters (ALP, ALT, and AST), hepatic lipid peroxidation (MDA and NO), and proliferating cell nuclear antigen (PCNA) indicating DNA damage. Moreover, AFB1 caused suppression of antioxidant biomarkers (SOD, GHS, GSH-Px, and CAT). However, the elevated serum levels of biochemical parameters and PCNA expression were reduced by SP. Moreover, SP lowered oxidative stress and lipid peroxidation markers in a dose-dependent manner. To sum up, SP supplementation is capable of decreasing AFB1 toxicity through its powerful antioxidant activity. [Display omitted] • Aflatoxin B1 induced hepatic oxidative injury. • Aflatoxin B1 induced liver DNA damage. • Spirulina platensis ameliorates Aflatoxin B-induced liver injury. • Spirulina platensis enhances DNA repair due to aflatoxin B- intoxication. • Spirulina platensis had antioxidant and anti-mycotoxin properties. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is one of the fundamental causes of ischemia reperfusion (I/R) damage. I/R refers to the paradoxical progression of cellular dysfunction and death that occurs when blood flow is restored to previously ischemic tissues. I/R causes a significant rise in mitochondrial permeability resulting in the opening of mitochondrial permeability transition pores (MPTP). The MPTP are broad, nonspecific channels present in the inner mitochondrial membrane (IMM), and are known to mediate the deadly permeability alterations that trigger mitochondrial driven cell death. Protection from reperfusion injury occurs when long-term ischemia is accompanied by short-term ischemic episodes or inhibition of MPTP from opening via mitochondrial ATP dependent potassium (mitoK ATP) channels. These channels located in the IMM, play an essential role in ischemia preconditioning (PC) and protect against cell death by blocking MPTP opening. This review primarily focuses on the interaction between the MPTP and mitoK ATP along with their role in the I/R injury. This article also describes the molecular composition of the MPTP and mitoK ATP in order to promote future knowledge and treatment of diverse I/R injuries in various organs. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) toxicity is associated with extensive neuronal degeneration of dorsal root ganglia (DRG). This study aimed to assess the ameliorative effect of bee venom (BV) on methyl mercury chloride (MeHgCl)-induced peripheral neurotoxicity using DRGs in rats. Forty-eight adult male Sprague Dawley rats were allocated into four equal groups: G I: control (gavaged MilliQ water 1 ml/rat), G II: subcutaneously injected with BV (0.5 mg/kg b.wt), G III: gavaged MeHgCl (6.7 mg/kg b.wt), and G IV: received MeHgCl+BV. Dosing was done five times/week for 2 weeks. Ataxic behavior and visual impairments were significantly increased, whereas the movement behavior and motility gait were suppressed in the MeHgCl group. MeHgCl significantly decreased total antioxidant capacity (TAC) in DRG and significantly decreased the serum levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) levels were significantly elevated, whereas interleukin 10 (IL-10) levels were significantly decreased in the MeHgCl group compared with the control group. DRGs of the MeHgCl-exposed rats showed pyknotic shrunken neurons with perineural vacuolations, demyelination of nerve axons, and proliferation of the satellite cells. MeHgCl significantly induced a higher positive index ratio of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin immunostaining in the DRG. BV administration significantly mitigated the MeHgCl-induced alterations in oxidative stress-related indices. BV modified the immunostaining of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin-positive index ratio in the DRG of the MeHgCl group. Our findings acknowledged that BV could enhance in vivo neuroprotective effects against MeHgCl-induced DRGs damage in male rats. • Bee venom ameliorates dorsal root ganglia neural (DRG) degeneration induced by methyl mercury. • Bee venom modifies neuro-behavioral alterations induced by methyl mercury in male rats. • Bee venom suppressed serum inflammatory cytokines induced by methyl mercury in rats. • Bee venom boosts the antioxidants serum levels of SOD, CAT, and GSH altered by methyl mercury. • Methyl mercury altered Iba1, Sox10, neurofilament, pan neuron, and vimentin expression in DRG. [ABSTRACT FROM AUTHOR]

Diabetes has become more common in recent years worldwide, and this growth is projected to continue in the future. The primary concern with diabetes is developing various complications, which significantly contribute to the disease's mortality and morbidity. Over time, the condition progresses from the pre-diabetic to the diabetic stage and then to the development of complications. Years and enormous resources are required to evaluate pharmacological interventions to prevent or delay the progression of disease or complications in humans. Appropriate screening models are required to gain a better understanding of both pathogenesis and potential therapeutic agents. Different species of animals are used to evaluate the pharmacological potentials and study the pathogenesis of the disease. Animal models are essential for research because they represent most of the structural, functional, and biochemical characteristics of human diseases. An ideal screening model should mimic the pathogenesis of the disease with identifiable characteristics. A thorough understanding of animal models is required for the experimental design to select an appropriate model. Each animal model has certain advantages and limitations. The present manuscript describes the animal models and their diagnostic characteristics to evaluate microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme is one of the most deadly malignant tumors, with more than 10,000 cases recorded annually in the United States. Various clinical analyses and studies show that certain chronic diseases, including cancer, interact between cell-reactive radicals rise and pathogenesis. Reactive oxygen and nitrogenous sources include endogenous (physiological processes), and exogenous sources contain reactive oxygen and nitrogen (xenobiotic interaction). The cellular oxidation/reduction shifts to oxidative stress when the regulation mechanisms of antioxidants are surpassed, and this raises the ability to damage cellular lipids, proteins, and nucleic acids. This review is focused on how phytochemicals play crucial role against glioblastoma multiforme and to combat these, bioactive molecules and their derivatives are either used alone, in combination with anticancer drugs or as nanomedicine formulations for better cancer theranostics over the conventional approach. Bioactive molecules found in seeds, vegetables, and fruits have antioxidant, anti-inflammatory, and anticancer properties that may help cancer survivors feel better throughout chemotherapy or treatment. However, incorporating them into the nanocarrier-based drug delivery for the treatment of GBMs, which could be a promising therapeutic strategy for this tumor entity, increasing targeting effectiveness, increasing bioavailability, and reducing side effects with this target-specificity, drug internalization into cells is significantly improved, and off-target organ aggregation is reduced. [Display omitted] • Bioactive molecules are the best approach in GBM. • Bioactive molecules effective against GBM. • Phytonanocarriers enhanced the bioavailability and reduced severe side effects. • Target-specificity and drug internalization into cells is significantly improved. [ABSTRACT FROM AUTHOR]

Oral mucocutaneous cancers (OMCs) are cancers that affect both the oral mucosa and perioral cutaneous structures. Common OMCs are squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and malignant melanoma (MM). Anatomical similarities and conventions which categorizes these lesions blur the magnitude of OMCs in diverse populations. The burden of OMC is high in the sub-Saharan Africa and Indian subcontinents, and the cost of management is prohibitive in the resource-limited, developing world. Hence, there is a pressing demand for the use of cost-effective in silico approaches to identify diagnostic tools and treatment targets for diseases with high burdens in these regions. Due to their ubiquitousness and accessibility, the use of therapeutic efficacy of plant bioactive compounds in the management of OMC is both appropriate and plausible. Furthermore, screening known mechanistic disease targets with well annotated plant bioactive compound libraries is poised to improve the routine management of OMCs provided that the requisite access to database resources are available and accessible. Using natural products minimizes the side effects and morbidities associated with conventional therapies. The development of innovative treatments approaches would tremendously benefit the African and Indian populace and reduce the mortalities associated with OMCs in the developing world. Hence, we discuss herein, the potential benefits, opportunities and challenges of using bioactive compound libraries in the management of OMCs. [Display omitted] • Comprehensive review of the bioactive compounds and their libraries. • Extraction of bioactive phyto-chemicals. • Biomedical Applications of Plant Derived Bioactive Compounds. • Commercially accessible plant derived compounds for treating oral cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: The biological activity of quercetin is diverse, particularly antioxidant, antimicrobial, and antibacterial. The impacts of quercetin nutritional supplementations on growth performance, humoral immunity, gut microbiota and mRNA in broiler chickens were recorded. Quercetin was fed to groups of broiler chickens at concentrations of 200, 400, and 800 ppm, and a control group was supplemented with a basal diet. Results revealed that quercetin dietary supplementation numerically improved the growth performance traits and significantly increased (p < 0.05) the European production efficiency factor (EPEF) in the 200 ppm group. The total coliforms and Clostridium perfringens were decreased (p < 0.05) in quercetin-supplemented groups. Conversely, Lactobacillus counts were increased (p < 0.05), due to improvement of the gut microbiota environment in quercetin-supplemented groups. Moreover, the mRNA expression of intestinal Cu/Zn-superoxide dismutase (SOD1), glutathione peroxidase (GSH-Px) and nutritional transporters, including glucose transporter 2 (GLUT2), peptide transporter 1 (PEPT1), and fatty acid synthase (FAS) genes, were significantly upregulated in quercetin-supplemented groups. Quercetin enhanced intestinal morphometry. We can suggest quercetin supplementation in broiler chickens by levels between 200 and 400 ppm to enhance their development and gut environment. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are the primary cause of disabilities in the elderly people. Growing evidence indicates that oxidative stress, mitochondrial dysfunction, neuroinflammation and apoptosis are associated with aging and the basis of most neurodegenerative disorders. Quercetin is a flavonoid with significant pharmacological effects and promising therapeutic potential. It is widely distributed among plants and typically found in daily diets mainly in fruits and vegetables. It shows a number of biological properties connected to its antioxidant activity. Neuroprotection by quercetin has been reported in many in vitro as well as in in vivo studies. However, the exact mechanism of action is still mystery and similarly there are a number of hypothesis exploring the mechanism of neuroprotection. Quercetin enhances neuronal longevity and neurogenesis by modulating and inhibiting wide number of pathways. This review assesses the food sources of quercetin, its pharmacokinetic profile, structure activity relationship and its pathophysiological role in various NDDs and it also provides a synopsis of the literature exploring the relationship between quercetin and various downstream signalling pathways modulated by quercetin for neuroprotection for eg. nuclear factor erythroid 2-related factor 2 (Nrf2), Paraoxonase-2 (PON2), c-Jun N-terminal kinase (JNK), Tumour Necrosis Factor alpha (TNF-α), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α), Sirtuins, Mitogen-activated protein kinases (MAPKs) signalling cascades, CREB (Cyclic AMP response element binding protein) and Phosphoinositide 3- kinase(PI3K/Akt). Therefore, the aim of the present review was to elaborate on the cellular and molecular mechanisms of the quercetin involved in the protection against NDDs. [ABSTRACT FROM AUTHOR]

Cancer treatment is improving widely over time, but finding a proper defender to beat them seems like a distant dream. The quest for identification and discovery of drugs with an effective action is still a vital work. The role of a membrane protein called P-glycoprotein, which functions as garbage chute that efflux the waste, xenobiotics, and toxins out of the cancer cells acts as a major reason behind the therapeutic failure of most chemotherapeutic drugs. In this review, we mainly focused on a multiple strategies by employing 5-Fluorouracil, curcumin, and lipids in Nano formulation for the possible treatment of colorectal cancer and its metastasis. Eventually, multidrug resistance and angiogenesis can be altered and it would be helpful in colorectal cancer targeting.We have depicted the possible way for the depletion of colorectal cancer cells without disturbing the normal cells. The concept of focusing on multiple pathways for marking the colorectal cancer cells could help in activating one among the pathways if the other one fails. The activity of the 5-Fluorouracil can be enhanced with the help of curcumin which acts as a chemosensitizer, chemotherapeutic agent, and even for altering the resistance. As we eat to survive, so do the cancer cells. The cancer cells utilize the energy source to stay alive and survive. Fatty acids can be used as the energy source and this concept can be employed for targeting the colorectal cancer cells and also for altering the resistant part. [Display omitted] • Colorectal cancer treatment failure is multidrug resistance and reoccurrence. • Resistance exhibits with the action of P-glycoprotein, which results in metastasis. • Lipids, 5-Fluorouracil and curcumin combination relapse colorectal cancer. • This dual drug approach provides a synergistic activity. • Focusing on metastasis with lymph node targeting with lipids. [ABSTRACT FROM AUTHOR]

Cancer is one of the most dreaded diseases characterized by uncontrolled proliferation of abnormal cells that occurs due to impairment of cell division and apoptosis process. Cancer is categorized into several types on the basis of affected organs and breast cancer (BC) is the most predominant cause of mortality among women. Although, several synthetic and semi-synthetic therapies have been developed for the treatment of BC but they exhibit numerous serious adverse effects therefore; pharmacological agents with fewer/no side effects need to be explored. Plants and phytoconstituents perhaps fulfill the aforementioned requirement and could serve as a potential and alternative therapy for BC treatment. The ongoing biomedical research, clinical trials and number of patents granted have further boosted the acceptance of the plants and plant-derived constituents in the effective treatment of BC. Various treatment strategies such as checkpoint inhibitors, targeting micro RNA, apoptotic pathway, BRCA-1 gene, P 53 protein, P13K/Akt/mTOR pathway, notch signaling pathway, hedgehog/gli-1 signaling pathway, poly-ADP ribose polymerase inhibitors, mitogen-activated protein kinase inhibitors etc. are available for BC. In addition to these synthetic and semi-synthetic drug therapies, several natural constituents such as alkaloids, sesquiterpenes, polyphenols, flavonoids and diterpenoids from medicinal plants, vegetables and fruits are reported to possess promising anti-cancer activity. The purpose of the present review is to highlight the various signaling pathways through which plants/herbs show the anti-cancer potential especially against the BC. The literature for the present study was collected from various databases such as Pubmed, Scopus, Chemical Abstracts, Medicinal and aromatic plant abstracts, Web of Science etc. The different patent databases were also reviewed for the anti-cancer (BC) potential of the particular herbs/plants and their formulations. In this review, we have discussed the number of plants along with their patents of different herbal formulations which are being used for the treatment of BC and other types of cancers. We have also delineated the different signaling mechanisms through which they inhibit the growth of BC cells. In nutshell, we can conclude that large numbers of herbs or their extracts are reported for the treatment of BC. But still, there is further need for research in-depth to translate the use of natural products clinically BC treatment. [Display omitted] • 90–95% cases of breast cancer (BC) occurs due to mutation in tumor suppressor genes. • Hormone receptor-positive BC, human epidermal growth factor-2 positive BC, triple-negative BC, Claudin-low subtype BC are types of breast cancer. • Various treatment strategies are available for the treatment of breast cancer. • Signaling mechanisms of various plants are patented for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an incurable, neuropsychiatric, pathological condition that deteriorates the worth of geriatric lives. AD is characterized by aggregated senile amyloid plaques, neurofibrillary tangles, neuronal loss, gliosis, oxidative stress, neurotransmitter dysfunction, and bioenergetic deficits. The changes in GIT composition and harmony have been recognized as a decisive and interesting player in neuronal pathologies including AD. Microbiota control and influence the oxidoreductase status, inflammation, immune system, and the endocrine system through which it may have an impact on the cognitive domain. The altered and malfunctioned state of microbiota is associated with minor infections to complicated illnesses that include psychosis and neurodegeneration, and several studies show that microbiota regulates neuronal plasticity and neuronal development. The altered state of microbiota (dysbiosis) may affect behavior, stress response, and cognitive functions. Chronic stress-mediated pathological progression also has a well-defined role that intermingles at various physiological levels and directly impacts the pathological advancement of AD. Chronic stress-modulated alterations affect the well-established pathological markers of AD but also affect the gut–brain axis through the mediation of various downstream signaling mechanisms that modulate the microbial commensals of GIT. The extensive literature reports that chronic stressors affect the composition, metabolic activities, and physiological role of microbiota in various capacities. The present manuscript aims to elucidate mechanistic pathways through which stress induces dysbiosis, which in turn escalates the neuropathological cascade of AD. The stress–dysbiosis axis appears a feasible zone of work in the direction of treatment of AD. [ABSTRACT FROM AUTHOR]

Mesoporous carbon is a promising material having multiple applications. It can act as a catalytic support and can be used in energy storage devices. Moreover, mesoporous carbon controls body's oral drug delivery system and adsorb poisonous metal from water and various other molecules from an aqueous solution. The accuracy and improved activity of the carbon materials depend on some parameters. The recent breakthrough in the synthesis of mesoporous carbon, with high surface area, large pore-volume, and good thermostability, improves its activity manifold in performing functions. Considering the promising application of mesoporous carbon, it should be broadly illustrated in the literature. This review summarizes the potential application of mesoporous carbon in many scientific disciplines. Moreover, the outlook for further improvement of mesoporous carbon has been demonstrated in detail. Hopefully, it would act as a reference guidebook for researchers about the putative application of mesoporous carbon in multidimensional fields. [ABSTRACT FROM AUTHOR]

Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including IκB kinase β (IκKβ), tumor necrosis factor-alpha (TNF-α), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-κB), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a gradually growing irreversible illness of the brain that almost affects every fifth person (aged > 80 years) in the world. World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030. The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder. Natural inhibitors of acetylcholine (ACh) such as galanthamine and rivastigmine are used commercially in the treatmentof AD. The biomolecules such assesquiterpenes, possess a great structural diversity and are responsible for a plethora of pharmacological properties. The potential of various sesquiterpenes as anticholinesterase has been reviewed in this article. For this purpose, the various databases, mainly PubMed, Scopus, and Web of Science were investigatedwith different keywords such as "sesquiterpenes+acetylcholinesterase" and "sesquiterpenes+cholinesterase+inhibitors" in the surveyed time frame (2010–2020). A vast literature was evident in the last decade, which affirms the potential of various sesquiterpenes in the improvement of cholinergic transmission by inhibiting the AChE. After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9 μM and can be considered as potential candidates for the improvement of learning and memory. Sesquiterpene is an important category of terpenoids, found to possess a large spectrum of biological activities. The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol, etc.) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD. [ABSTRACT FROM AUTHOR]

Thermal stress is known to have harmful effects on livestock productivity and can cause livestock enterprises considerable financial loss. These effects may be aggravated by climate change. Stress responses to nonspecific systemic actions lead to perturbation of molecular pathways in the organism. The molecular response is regulated in a dynamic and synchronized manner that assurances robustness and flexibility for the restoration of functional and structural homeostasis in stressed cells and tissues. MicroRNAs (miRNAs) are micro molecules of small non-coding RNA that control gene expression at the post-transcriptional level. Recently, various studies have discovered precise types of miRNA that regulate cellular machinery and homeostasis under various types of stress, suggesting a significant role of miRNA in thermal stress responses in animals. The miRNAs revealed in this paper could serve as promising candidates and biomarkers for heat stress and could be used as potential pharmacological targets for mitigating the consequences of thermal stress. Stress miRNA pathways may be associated with thermal stress, which offers some potential approaches to combat the negative impacts of thermal stress in livestock. The review provides new data that can assist the elucidation of the miRNA mechanisms that mediate animals' responses to thermal stress. • Heat stress disturbs organisms and damages their molecular pathways. • miRNAs in regulating cellular machinery and homeostasis under heat stress conditions. • miRNAs could serve as promising candidates and biomarkers for heat stress. [ABSTRACT FROM AUTHOR]