Association of interleukin-17F (rs763780) single nucleotide polymorphism with multiple sclerosis and optic neuritis.

IL-17F single nucleotide polymorphism (SNP) can affect IL-17F expression and activity and this can lead to the increased susceptibility to several autoimmune diseases. The aim was to investigate the association of IL-17F (rs763780) SNP with the development of multiple sclerosis (MS) in a cohort of Egyptian patients and to evaluate the effect of this polymorphism on the disease course. IL-17F (rs763780) gene polymorphisms was typed by TaqMan genotyping assay for 231 Egyptians divided into 102 MS patients and 129 healthy controls with matched age and sex. The IL-17F rs763780 C containing genotypes (CT+CC) and C allele have statistically significant increased frequency in MS patients when compared with controls (p = 0.005 and 0.004 respectively) especially in females' patients (p = 0.005 and 0.006 respectively). The heterozygous CT genotype was associated with the presence of optic neuritis (p = 0.038). The multivariable regression analysis revealed significant associations between smoking, the higher frequency of attacks and the prediction of higher EDSS score (p = 0.032, 0.049 respectively). It can be concluded that the IL-17F rs763780 C containing genotypes (CT and CC) and C allele may be risk factors for the development of MS in the studied Egyptian cohort by a gender-dependent mechanism that contributes to tendency for predisposition in females and optic neuritis is more common in patients carrying the CT heterozygous genotype.

Chemical, electrochemical, and quantum investigation into the use of an organophosphorus derivative to inhibit copper corrosion in acidic environments.

In order to protect the copper against corrosion, a novel corrosion inhibitor known as diphenyl ((2-aminoethyl) amino) (4-methoxyphenyl) methyl) phosphonate (DAMP) was developed. Acid solutions of HCl and H2SO4 were the aggressive solutions employed in this study. Analysis using the FT-IR, 1H-NMR, 31P-NMR, 13C-NMR and BET confirmed that the DAMP was successfully synthesized. The anti-corrosion capabilities of DAMP are evaluated using a combination of chemical, electrochemical and quantum studies. The DAMP has been found to be crucial in preventing the corrosion of copper in both HCl and H2SO4 acid. This was obviously implied by the observation that the corrosion rate of copper in acid solutions decreased when DAMP was added. It is significant to note that 180 ppm produced the highest levels of inhibiting efficiency (96.6% for HCl and 95.2% for H2SO4). The tendency of DAMP to adsorb on the surface of copper through its hetero-atoms (O, N, and P) is the main factor for the anti-corrosion capabilities of DAMP. Results from SEM/EDX tests supported this. The actual adsorption takes place via various active centers, physical and chemical mechanisms that are coordinated with the estimated quantum parameters. Additionally, the adsorption of DAMP adheres to the Langmuir isotherm.

Spatio-Temporal Pattern of Tuberculosis Distribution in Romania and Particulate Matter Pollution Associated With Risk of Infection.

The study proposes a dynamic spatio-temporal profile of the distribution of tuberculosis incidence and air pollution in Romania, where this infectious disease induces more than 8,000 new cases annually. The descriptive analysis for the years 2012-2021 assumes an identification of the structuring patterns of mycobacterium tuberculosis risk in the Romanian population, according to gender and age, exploiting spatial modeling techniques of time series data. Through spatial autocorrelation, the degree of similarity between the analyzed territorial systems was highlighted and the relationships that are built between the analysis units in spatial proximity were investigated. By modeling the geographical distribution of tuberculosis, the spatial correlation with particulate matter (PM2.5) pollution was revealed. The identification of clusters of infected persons is an indispensable step in the construction of efficient tuberculosis management systems. The results highlight the link between the distribution of tuberculosis, air pollution and socio-economic development, which requires a detailed analysis of the epidemiological data obtained in the national tuberculosis surveillance and control program from the perspective of geographical distribution.

Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma.

Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of GPNMB in the in vivo tumor microenvironment results in significantly smaller tumor volumes and generates a pro-inflammatory innate and adaptive immune cell microenvironment. The impact of host-derived GPNMB on tumor growth was confirmed in two distinct murine glioma cell lines in organotypic brain slices from GPNMB-KO and control mice. Using published data bases of human glioma, the elevated levels in TAMs could be confirmed and the GPNMB expression correlated with a poorer survival.

Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans.

BACKGROUND: Candida albicans is a fungal pathogen causing human infections. Here we investigated differential gene expression patterns and functional enrichment in C. albicans strains grown under different conditions. METHODS: A systematic GEO database search identified 239 "Candida albicans" datasets, of which 14 were selected after rigorous criteria application. Retrieval of raw sequencing data from the ENA database was accompanied by essential metadata extraction from dataset descriptions and original articles. Pre-processing via the tailored nf-core pipeline for C. albicans involved alignment, gene/transcript quantification, and diverse quality control measures. Quality assessment via PCA and DESeq2 identified significant genes (FDR < = 0.05, log2-fold change > = 1 or <= -1), while topGO conducted GO term enrichment analysis. Exclusions were made based on data quality and strain relevance, resulting in the selection of seven datasets from the SC5314 strain background for in-depth investigation. RESULTS: The meta-analysis of seven selected studies unveiled a substantial number of genes exhibiting significant up-regulation (24,689) and down-regulation (18,074). These differentially expressed genes were further categorized into 2,497 significantly up-regulated and 2,573 significantly down-regulated Gene Ontology (GO) IDs. GO term enrichment analysis clustered these terms into distinct groups, providing insights into the functional implications. Three target gene lists were compiled based on previous studies, focusing on central metabolism, ion homeostasis, and pathogenicity. Frequency analysis revealed genes with higher occurrence within the identified GO clusters, suggesting their potential as antifungal targets. Notably, the genes TPS2, TPS1, RIM21, PRA1, SAP4, and SAP6 exhibited higher frequencies within the clusters. Through frequency analysis within the GO clusters, several key genes emerged as potential targets for antifungal therapies. These include RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101 which exhibited higher occurrence within the identified clusters. CONCLUSION: This comprehensive study significantly advances our understanding of the dynamic nature of gene expression in C. albicans. The identification of genes with enhanced potential as antifungal drug targets underpins their value for future interventions. The highlighted genes, including TPS2, TPS1, RIM21, PRA1, SAP4, SAP6, RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101, hold promise for the development of targeted antifungal therapies.

The ionic liquids upon perchlorate to promote the C-C/C-O bonds cleavage in alkali lignin under photothermal synergism.

Transforming lignin into aromatic monomers is critically attractive to develop green and sustainable energy supplies. However, the usage of the additional catalysts like metal or base/acid is commonly limited by the caused repolymerized and environmental issues. The key step is to mediate electron transfer in lignin to trigger lignin C-C/C-O bonds cleavage without the catalysts mentioned above. Here, we report that the ionic liquids [BMim][ClO4] was found to trigger lignin electron transfer to cleave the C-C/C-O bonds for aromatic monomers without any additional catalyst. The proton transfer from [BMim]+ to [ClO4]- could polarize the anion and decrease its structure stability, upon which the active hydroxyl radical generated and induced lignin C-C/C-O bonds fragmentation via free radical-mediated routes with the assistance of photothermal synergism. About 4.4 wt% yields of aromatic monomers, mainly composed of vanillin and acetosyringone, are afforded in [BMim][ClO4] under UV-light irradiation in the air at 80 °C. This work opens the way to produce value-added aromatic monomers from lignin using an eco-friendly, energy-efficient, and simple route that may contribute to the sustainable utilization of renewable natural resources.

YouTube as a source of patient information on awake craniotomy: Analysis of content quality and user engagement.

•Most YouTube videos on awake craniotomy are of poor educational value.•Intraoperative musical performances by patients are the strongest driver of video popularity.•User engagement of awake craniotomy videos is not linked to their educational quality.•Patients must be aware of the high prevalence of misleading content on YouTube.•Patients may require guidance in choosing the best resources online.

Immunomodulatory and anti-cancer potential of cloves (Syzygium aromaticum) bud extract and its phytogenic silver nanoparticles.

Clove plant (Syzygium aromaticum) is one of the Myrtaceae family. It's a common flavor in food and the traditional medicine. The study's objective was to ascertain whether the clove bud aqueous extract (CAE) and CAE + nanosilver have any biological effects on immune cells and HT-29 colon cancer cell line. Nanosilver was produced through green synthesis approach using CAE. Produced nanosilver was characterized via electron microscope (scanning, SEM) and ultraviolet-visible spectroscopy. CAE and CAE + nanosilver were examined for their active biomolecules using FTIR analysis, p53 contents using real-time PCR, apoptosis and cell cycle arrest power on HT-29 cancer cell line via flow cytometerty and immunomodulatory potential utilizing MTT assay. Results cleared that a spherical nanosilver with a diameter range of 53 nm was formed by CAE. There were several active biomolecules in CAE and CAE + nanosilver. CAE and CAE + nanosilver increased the p53 protein expression and apoptotic cell number in HT-29 colon cancer cells. CAE and CAE + nanosilver could arrest HT-29 cells at the phase G2/M. CAE and CAE + nanosilver stimulated quiescent and PHA-pre-treated splenic cells at higher concentrations, and CAE suppressed quiescent splenic cell when diluted. In conclusion, the safe edible Syzygium aromaticum plant can be utilized to make anti-tumor agent, essentially for colon tumor. As Syzygium aromaticum plant could stimulate immune cells, it can be used as immune-stimulatory agent that can help fight tumor and tumor development.

Overview of solar thermal applications of heat exchangers with thermophysical features of hybrid nanomaterials.

With their notable thermal characteristics, fluids incorporating nanoparticles have significant importance in industrial processes. Due to the higher proficiency of hybrid nanofluid, this study is organized to observe the flow phenomenon and thermal characteristics of kerosene-oil-based hybrid ferrofluid in relation to the modified versions of two imperative Yamada-Ota and Xue models. A performance-based comparison is conducted for an incompressible hybrid ferrofluid in relation to the upgraded Yamada-Ota and Xue models. The magnetized flow mechanism in two dimensions is explored over a stretchable, curved sheet. With the ordinary kerosene oil liquid, the ferroparticles, namely cobalt ferrite and magnetite, are merged to form (CoFe2O4-Fe3O4/kerosene oil) hybrid ferrofluid. Mass and heat transport mechanisms are scrutinized with the execution of activation energy, convective constraints, Joule heating, exponential heat sources, and thermal radiation. Suitable ansatzes are utilized to achieve the dimensionless pattern of the equations that regulate the problem. To numerically explore the dimensionless equations, a powerful bvp4c strategy is implemented. On behalf of both considered models, the characteristics of hybrid ferrofluid relative to pertinent parameters are graphically investigated and comparatively analyzed. This study ensures that the improved Yamada-Ota model yields more proficient outcomes in comparison to the Xue model. Moreover, the concentration field demonstrates an escalating trend with the enhanced activation energy parameter.

Neurofibromin 1 mutations impair the function of human induced pluripotent stem cell-derived microglia.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by germline mutations in the neurofibromin 1 (NF1) gene. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could reflect the effect of NF1 mutation on microglia function. Using heterozygous Nf1-mutant mice, we previously demonstrated that impaired purinergic signaling underlies deficits in microglia process extension and phagocytosis in situ. To determine whether these abnormalities are also observed in human microglia in the setting of NF1, we leveraged an engineered isogenic series of human induced pluripotent stem cells to generate human microglia-like (hiMGL) cells heterozygous for three different NF1 gene mutations found in patients with NF1. Whereas all NF1-mutant and isogenic control hiMGL cells expressed classical microglia markers and exhibited similar transcriptomes and cytokine/chemokine release profiles, only NF1-mutant hiMGL cells had defects in P2X receptor activation, phagocytosis and motility. Taken together, these findings indicate that heterozygous NF1 mutations impair a subset of the functional properties of human microglia, which could contribute to the neurological abnormalities seen in children with NF1.

The Effect of Helicobacter pylori Density on Serum Vitamin B12 and Folate Levels in Patients With Non-atrophic Gastritis.

Introduction Chronic infection with Helicobacter pylori (Hp) is an essential cause of gastrointestinal pathologies in adults. Despite being a microorganism proven to play a role in vitamin B12 deficiency by causing gastric atrophy, Hp's role in patients with non-atrophic gastritis has not been fully explained. Our study investigated whether the presence and density of Hp is related to vitamin B12 and folate deficiencies in patients with non-atrophic gastritis. Methods This retrospective cohort study analyzed the following parameters, vitamin B12, folate, and mean red blood cell volume (MCV) in the hemogram; these were measured simultaneously in patients diagnosed with non-atrophic gastritis who had undergone gastroscopy to investigate Hp levels. Patients with conditions that could have caused vitamin B12 and folate deficiencies were excluded from the study. The study included 244 patients who met the criteria. The Sydney classification was used for histopathologic grading and staging of gastric biopsies of patients with gastritis. Results There was no relationship between the presence and density of Hp with vitamin B12 levels. However, folate levels were significantly lower in Hp-positive patients than in Hp-negative patients (p = 0.017). Folate levels were substantially lower in patients with chronic pan-mucosal gastritis than in patients with chronic inactive gastritis (p = 0.034). Statistically, a significant difference was found between folate levels on the basis of neutrophil activity and inflammation score (p = 0.011 and p <0.001, respectively). Conclusions Although there was no statistically significant relationship between the presence and density of Hp and vitamin B12, our study found an association between folate levels and Hp density. This may be associated with the time for the depletion of vitamin B12 and folate stores and the relatively early stage of gastritis. In cases with vitamin B12 and folate deficiencies, appropriate studies should be performed for specific epidemiological reasons in respective fields.

Management of sunflower charcoal-rot and maize late-wilt diseases using the aqueous extract of vermicompost (vermitea) and environmental-safe biochar derivative (wood vinegar).

In Egypt, sunflower charcoal-rot caused by Macrophomina phaseolina and maize late-wilt caused by Magnaporthiopsis maydis are the most prevalent, and can lead to huge yield losses of both crops under epidemic conditions. In this study, the potential use of vermitea and wood vinegar for management of both diseases was investigated. Data revealed that, among the 17 bacterial strains obtained from vermitea, three strains named VCB-2, VCB-7 and VCB-11 were chosen for having the greatest in vitro inhibitory effect against M. phaseolina and M. maydis, with fungal inhibition values of 54.2; 61.7, 65.2; 74.0 and 57.1; 87.0% against both pathogens, respectively. These strains were identified as Bacillus amyloliquefaciens, Serratia marcescens and Bacillus velezensis, respectively. Wood vinegar significantly reduced the colony diameter of M. phaseolina and M. maydis in in vitro trials conducted on potato dextrose agar medium amended with the desired concentrations of 0.5, 1.0, 1.5, 2.0, and 2.5%. The efficiency increased with increasing wood vinegar concentration, and 2.0% was the most effective (100% suppression). Data from greenhouse experiments showed that the application of vermitea or wood vinegar tended to decrease the incidence (% dead plants) of sunflower charcoal-rot (by 61.1 and 66.7%) and maize late-wilt (by 70.6%). These treatments had positive impacts on the plant growth parameters, photosynthetic pigments and antioxidative enzymes of sunflower and maize plants. Data from field experiments showed that the application of vermitea or wood vinegar decreased the incidence of charcoal-rot (by 72.8 and 72.0%) and late-wilt (by 88.7 and 87.0%) as well as increased the production sunflower and maize plants.

Surgical Management of Temporal Lobe Epilepsy Secondary to Epidermoid Cysts: A Case Report With Review of the Literature.

Epidermoid cysts represent roughly 1% of all intracranial tumors. They are frequently located in the cerebellopontine angle but rarely extend to the supratentorial brain. Epilepsy is an extremely uncommon manifestation of this neoplasm. We suggest the surgical management of a 35-year-old male who presented with a six-month history of intractable temporal lobe epilepsy. His seizures were characterized by a focal onset in the form of déjà vu experiences, followed by a secondarily generalized tonic-clonic seizure. Imaging revealed a heterogeneous cystic mass in the right cerebellopontine angle, extending supratentorially causing a mass effect on the mesial temporal region. Gross total resection was achieved through a combined subtemporal-retrosigmoid approach. Histopathology revealed an epidermoid cyst. The patient was entirely seizure-free at the three-month follow-up. Epidermoid cysts may present with epileptic seizures. Seizure freedom can be achieved with surgical management in most cases. The patient's symptoms, imaging findings, and epileptogenic focus must be considered to select the appropriate surgical strategy.

Darcy flow of convective and radiative Maxwell nanofluid over a porous disk with the influence of activation energy.

This study reveals an incompressible steady Darcy flow of Maxwell nanofluid by a porous disk with the impact of activation energy. The liquid flow is due to a stretchable rotating disk. The heat equation also includes the impact of heat source/sink and radiation for the purpose of heat transportation. The von Karman transformations are utilized to gain the dimensionless form of ordinary differential equations (ODEs). The solutions are visualised in the form of graphical results using bvp 4c method in Matlab software. The ranges of the associated physical parameters as, 0.0≤ß≤0.9, 0.0≤M≤0.9, 0.0≤λ≤1.5, 0.1≤R≤0.9, -0.2≤s≤1.3, 0.3≤Bi≤0.6, 0.0≤γ≤0.15, 0.1≤Nt≤2.0, 0.2≤Nb≤0.8, 0.0≤Rd≤0.3, 0.0≤σ≤1.5, and 0.0≤E≤0.9 are provided for the graphical solutions developed for the problem. The data of Nussetl and Sherwood numbers are presented here with regard to various physical parameters. According to the numerical results, increasing the Deborah number has a trend to decrease the radial curves. Moreover, the temperature distribution is increased considerably for rising the radiation parameter and the higher rate of the rotation parameter shows a weaker concentration trend. To validate the numerical approach, an excellent comparison is established using a tabular description. To sum up, the current study effectively fills a gap in the antecedent literature.

Neurosurgical Education Using Cadaver-Free Brain Models and Augmented Reality: First Experiences from a Hands-On Simulation Course for Medical Students.

Background and Objectives: Neurosurgery has been underrepresented in the medical school curriculum. Advances in augmented reality and 3D printing have opened the way for early practical training through simulations. We assessed the usability of the UpSurgeOn simulation-based training model and report first experiences from a hands-on neurosurgery course for medical students. Materials and Methods: We organized a two-day microneurosurgery simulation course tailored to medical students. On day one, three neurosurgeons demonstrated anatomical explorations with the help of life-like physical simulators (BrainBox, UpSurgeOn). The surgical field was projected onto large high-definition screens by a robotic-assisted exoscope (RoboticScope, BHS Technologies). On day two, the students were equipped with microsurgical instruments to explore the surgical anatomy of the pterional, temporal and endoscopic retrosigmoid approaches. With the help of the RoboticScope, they simulated five clipping procedures using the Aneurysm BrainBox. All medical students filled out a digital Likert-scale-based questionnaire to evaluate their experiences. Results: Sixteen medical students participated in the course. No medical students had previous experience with UpSurgeOn. All participants agreed that the app helped develop anatomical orientation. They unanimously agreed that this model should be part of residency training. Fourteen out of sixteen students felt that the course solidified their decision to pursue neurosurgery. The same fourteen students rated their learning experience as totally positive, and the remaining two rated it as rather positive. Conclusions: The UpSurgeOn educational app and cadaver-free models were perceived as usable and effective tools for the hands-on neuroanatomy and neurosurgery teaching of medical students. Comparative studies may help measure the long-term benefits of UpSurgeOn-assisted teaching over conventional resources.

Effect of dual tasking on postural control in individuals with schizophrenia.

OBJECTIVE: To investigate the effect of dual tasking on postural control in individuals with schizophrenia. METHODS: Fifteen outpatients with schizophrenia and 15 healthy controls were included. Postural control was assessed with postural sway velocity (PSV) using Balance Master System during three different tasks: single task (standing on a force platform), cognitive task (categorical verbal fluency) and motor task (holding a cup of water) in four conditions: on firm surface with eyes open (1) and closed (2), on foam surface with eyes open (3) and closed (4). RESULTS: Individuals with schizophrenia presented higher PSV during single standing on foam surface with eyes open and closed. During the cognitive task, they showed higher PSV on foam surface with eyes closed. During the motor task PSV in schizophrenia group was higher on firm surface with eyes closed and on foam surface with eyes open and closed. Individuals with schizophrenia showed higher PSV during cognitive task on firm surface with eyes closed compared to the single task. CONCLUSIONS: Dual tasking results in a deterioration in postural control in individuals with schizophrenia. A cognitive task specifically alters postural control in the absence of visual information suggesting a possible sensorimotor dysfunction in this population.

Surf Redfish-Based ZnO-NPs and Their Biological Activity with Reference to Their Non-Target Toxicity.

The marine environment is a rich source of bioactive compounds. Therefore, the sea cucumber was isolated from the Red Sea at the Al-Ain Al-Sokhna coast and it was identified as surf redfish (Actinopyga mauritiana). The aqueous extract of the surf redfish was utilized as an ecofriendly, novel and sustainable approach to fabricate zinc oxide nanoparticles (ZnO-NPs). The biosynthesized ZnO-NPs were physico-chemically characterized and evaluated for their possible antibacterial and insecticidal activities. Additionally, their safety in the non-target organism model (Nile tilapia fish) was also investigated. ZnO-NPs were spherical with an average size of 24.69 ± 11.61 nm and had a peak at 350 nm as shown by TEM and UV-Vis, respectively. XRD analysis indicated a crystalline phase of ZnO-NPs with an average size of 21.7 nm. The FTIR pattern showed biological residues from the surf redfish extract, highlighting their potential role in the biosynthesis process. DLS indicated a negative zeta potential (-19.2 mV) of the ZnO-NPs which is a good preliminary indicator for their stability. ZnO-NPs showed larvicidal activity against mosquito Culex pipiens (LC50 = 15.412 ppm and LC90 = 52.745 ppm) and a potent adulticidal effect to the housefly Musca domestica (LD50 = 21.132 ppm and LD90 = 84.930 ppm). Tested concentrations of ZnO-NPs showed strong activity against the 3rd larval instar. Topical assays revealed dose-dependent adulticidal activity against M. domestica after 24 h of treatment with ZnO-NPs. ZnO-NPs presented a wide antibacterial activity against two fish-pathogen bacteria, Pseudomonas aeruginosa and Aeromonas hydrophila. Histopathological and hematological investigations of the non-target organism, Nile tilapia fish exposed to 75-600 ppm ZnO-NPs provide dose-dependent impacts. Overall, data highlighted the potential applications of surf redfish-mediated ZnO-NPs as an effective and safe way to control mosquitoes, houseflies and fish pathogenic bacteria.

Three-dimensional MHD flow of hybrid material between rotating disks with heat generation.

In this study, we investigate the flow of electrically conducting hybrid nanofluid (Ag+Cu/H2O), due to rotating disks, along with thermal slip, heat generation, and viscous dissipation. The nonlinear differential system is modelled and transformed into dimensionless partial differential equations using suitable dimensionless variables. To obtain solutions for the considered model, a finite difference toolkit is implemented, and numerical solutions are achieved. Graphical results are presented to display the influences of different dimensionless variables on flow velocity and temperature. This research contributes to a better understanding of hybrid nanofluid flows and can inform the design of cooling systems and other practical applications.

Green innovation behaviour: Impact of industry 4.0 and open innovation.

Developing nations have motivated contemporary manufacturing companies to embrace green innovation and focus on smart technology that is sustainable to harness the growing economy and uplift the people. Although, scientific research in this direction has been neglected, and at the same time there are challenges to the attainment while meeting the need of the people. This study aims to investigate the impact of Industry 4.0, open innovation and green innovation performance on green innovation behaviour. To this end, a theoretical model was established. A quantitative research approach was applied in which survey data were utilized to capture 247 responses from different manufacturing companies in Malaysia. The model was tested using SmartPLSver3.0 to measure the structural relationship between variables. The findings indicate that Industry 4.0 and green innovation performance positively impact green innovation behaviour, compared to open innovation which has no impact. The impact of green innovation performance is found to be stronger when compared to Industry 4.0 and open innovation. Likewise, green innovation performance exhibits a substantial mediating impact between the exogenous variables and green innovation behaviour. The policy implication and conclusions are further discussed in the last section of the study.

Valuable effects of lactobacillus and citicoline on steatohepatitis: role of Nrf2/HO-1 and gut microbiota.

Non-alcoholic steatohepatitis (NASH) is a more dangerous form of chronic non-alcoholic fatty liver disease (NAFLD). In the current investigation, the influence of citicoline on high-fat diet (HFD)-induced NASH was examined, both alone and in combination with Lactobacillus (probiotic). NASH was induced by feeding HFD (10% sugar, 10% lard stearin, 2% cholesterol, and 0.5% cholic acid) to rats for 13 weeks and received single i.p. injection of streptozotocin (STZ, 30 mg/kg) after 4 weeks. Citicoline was given at two dose levels (250 mg and 500 mg, i.p.) at the beginning of the sixth week, and in combination with an oral suspension of Lactobacillus every day for eight weeks until the study's conclusion. HFD/STZ induced steatohepatitis as shown by histopathological changes, elevated serum liver enzymes, serum hyperlipidemia and hepatic fat accumulation. Moreover, HFD convinced oxidative stress by increased lipid peroxidation marker (MDA) and decreased antioxidant enzymes (GSH and TAC). Upregulation of TLR4/NF-kB and the downstream inflammatory cascade (TNF-α, and IL-6) as well as Pentaraxin, fetuin-B and apoptotic markers (caspase-3 and Bax) were observed. NASH rats also had massive increase in Bacteroides spp., Fusobacterium spp., E. coli, Clostridium spp., Providencia spp., Prevotella interrmedia, and P. gingivalis while remarkable drop in Bifidobacteria spp. and Lactobacillus spp. Co-treatment with citicoline alone and with Lactobacillus improve histopathological NASH outcomes and reversed all of these molecular pathological alterations linked to NASH via upregulating the expression of Nrf2/HO-1 and downregulating TLR4/NF-kB signaling pathways. These results suggest that citicoline and lactobacillus may represent new hepatoprotective strategies against NASH progression.