Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies.

Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

Dietary microalgal-fabricated selenium nanoparticles improve Nile tilapia biochemical indices, immune-related gene expression, and intestinal immunity.

BACKGROUND: Feed supplements, including essential trace elements are believed to play an important role in augmenting fish immune response. In this context, selenium nanoparticles (SeNPs) in fish diets via a green biosynthesis strategy have attracted considerable interest. In this investigation, selenium nanoparticles (SeNPs, 79.26 nm) synthesized from the green microalga Pediastrum boryanum were incorporated into Nile tilapia diets to explore its beneficial effects on the immune defense and intestinal integrity, in comparison with control basal diets containing inorganic Se source. Nile tilapia (No. 180, 54-57 g) were fed on three formulated diets at concentrations of 0, 0.75, and 1.5 mg/kg of SeNPs for 8 weeks. After the trial completion, tissue bioaccumulation, biochemical indices, antioxidant and pro-inflammatory cytokine-related genes, and intestinal histological examination were analyzed. RESULTS: Our finding revealed that dietary SeNPs significantly decreased (P < 0.05) serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and cholesterol, while increasing (P < 0.05) high-density lipoproteins (HDL). The Se concentration in the muscle tissues showed a dose-dependent increase. SeNPs at a dose of 1.5 mg/kg significantly upregulated intestinal interleukin 8 (IL-8) and interleukin 1 beta (IL-1ß) gene transcription compared with the control diet. Glutathione reductase (GSR) and glutathione synthetase (GSS) genes were significantly upregulated in both SeNPs-supplemented groups compared with the control. No apoptotic changes or cell damages were observed as indicated by proliferating cell nuclear antigen (PCNA) and caspase-3 gene expression and evidenced histopathologically. SeNPs supplementation positively affects mucin-producing goblet cells (GCs), particularly at dose of 1.5 mg/kg. CONCLUSION: Therefore, these results suggest that Green synthesized SeNPs supplementation has promising effects on enhancing Nile tilapia immunity and maintaining their intestinal health.

Dietary algal-sourced zinc nanoparticles promote growth performance, intestinal integrity, and immune response of Nile tilapia (Oreochromis niloticus).

BACKGROUND: Trace elements play a crucial role in fish nutrition, with zinc (Zn) being one of the most important elements. BIO-sourced zinc nanoparticles were synthesized using the green microalga Pediastrum boryanum (BIO-ZnNPs, 29.35 nm). 30 or 60 mg/ kg dry feed of the BIO-ZnNPs (BIO-ZnNPs30 and BIO-ZnNPs60) were mixed with the Nile tilapia (Oreochromis niloticus) basal diet and fed to the fish for 8 weeks to evaluate their impact on fish growth, digestion, intestinal integrity, antioxidative status, and immunity. RESULTS: A significant enhancement was observed in all investigated parameters, except for the serum protein profile. BIO-ZnNPs at 60 mg/kg feed elevated the activities of reduced glutathione (GSH) and catalase (CAT), enzymatic antioxidants, but did not induce oxidative stress as reflected by no change in MDA level. Fish intestinal immunity was improved in a dose-dependent manner, in terms of improved morphometry and a higher count of acid mucin-producing goblet cells. Interleukin-8 (IL-8) was upregulated in BIO-ZnNPs30 compared to BIO-ZnNPs60 and control fish groups, while no significant expressions were noted in tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFkB), and Caspase3 genes. CONCLUSION: Overall, BIO-ZnNPs inclusion at 60 mg/kg feed showed the most advantage in different scenarios, compared to BIO-ZnNPs at 30 mg/kg feed. The positive effects on growth and intestinal health suggest that BIO-ZnNPs supplementation of aquafeeds has many benefits for farmed fish.

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFRWT, EGFRT790M, and EGFRL858R).

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c. Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFRWT, EGFRT790M, and EGFRL858R where compound 10d was the best inhibitor with IC50 = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC50 = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs.

New 32 hexahydroquinoline (HHQ) analogues 6a­i, 8a­m, 10a­d, and 12a­f having the same features of EGFR inhibitors were synthesised in racemic mixtures.The antiproliferative activities were assessed towards 60 cancer cell lines which were efficiently inhibited by compound 10c.Compound 10d remarkably inhibited EGFR^WT, EGFR^T790M, and EGFR^L858R.Cell cycle analysis and Annexin V-based flow cytometry in the HOP-92 lung cancer cells were performed.The safety profile of compounds 10c and 10d was validated using normal human lung (IMR-90) cells.Molecular docking studies revealed that the S-isomers exhibited higher affinity than R-isomers to active sites.

Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models.

BACKGROUND: The widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature-lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4 nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)-were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model. RESULTS: The application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect. CONCLUSIONS: Overall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.

Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods.

The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. Recently, anisotropic ENM have become of increasing interest, but knowledge of their effects on the immune system is still limited. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres, and, thus, also different surface chemistries, to assess NLRP3 inflammasome activation. Next, the exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gene Set Enrichment Analysis revealed that gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. At the level of individual genes, downregulation of Paraoxonase-2, a protein that controls oxidative stress, was most notable. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation. Future studies should include particle uptake and intracellular localization.

Application of Molecularly Imprinted Polymers in the Analysis of Waters and Wastewaters.

The increase of the global population and shortage of renewable water resources urges the development of possible remedies to improve the quality and reusability of waste and contaminated water supplies. Different water pollutants, such as heavy metals, dyes, pesticides, endocrine disrupting compounds (EDCs), and pharmaceuticals, are produced through continuous technical and industrial developments that are emerging with the increasing population. Molecularly imprinted polymers (MIPs) represent a class of synthetic receptors that can be produced from different types of polymerization reactions between a target template and functional monomer(s), having functional groups specifically interacting with the template; such interactions can be tailored according to the purpose of designing the polymer and based on the nature of the target compounds. The removal of the template using suitable knocking out agents renders a recognition cavity that can specifically rebind to the target template which is the main mechanism of the applicability of MIPs in electrochemical sensors and as solid phase extraction sorbents. MIPs have unique properties in terms of stability, selectivity, and resistance to acids and bases besides being of low cost and simple to prepare; thus, they are excellent materials to be used for water analysis. The current review represents the different applications of MIPs in the past five years for the detection of different classes of water and wastewater contaminants and possible approaches for future applications.

Biochemical and molecular investigation of oxidative stress associated with urolithiasis induced by increased dietary calcium or protein in chickens.

This study was carried out to evaluate the effects of induced urolithiasis by high dietary calcium (Ca) or protein levels on biochemical analyte levels, redox status, selected inflammatory cytokines and histopathology in chickens. A total of 90 one-day-old white Hy-Line chicks were fed basal control diets containing 20% crude protein (CP) and 1% Ca until they reached 44 days of age. After that, the birds were divided into three groups (30 birds per group). All management factors (light, temperature, ventilation, stock density and diet) were identical among the three groups throughout the study except for the dietary Ca and protein percentages. Group I was fed a control diet containing 20% CP and 1% Ca, group II was fed a high-Ca diet containing 5% Ca, and group III was fed a high-protein diet containing 25% CP. Our findings clearly demonstrated that dietary imbalance (caused by high-Ca or high-CP levels) per se in chickens was physiologically harmful, as it was accompanied by post-mortem lesions; biochemical, redox status and histopathological alterations; and upregulation of inflammatory cytokines (interleukin (IL)-1ß and IL-6). In particular, the birds fed the high-Ca diet clearly exhibited the most obvious alterations in most of the endpoints. In conclusion, this study constitutes the first extensive investigation of the effects of high-Ca or high-protein diets induced urolithiasis on growth performance, redox status, inflammatory cytokine levels and pathological characterization in chickens.

Withania somnifera dietary supplementation improves lipid profile, intestinal histomorphology in healthy Nile tilapia (Oreochromis niloticus), and modulates cytokines response to Streptococcus infection.

Despite Withania somnifera (WS), stimulating effects have been investigated on many animal species, its role on lipid profile and intestinal histomorphology in healthy animals, and its modulating role on pro-inflammatory cytokines following infection in fish are yet scarce. In this context, lipid profile, liver, and intestinal histomorphology were measured in Nile tilapia fed with a basal diet or diets containing 2.5 and 5% of supplementary WS for 60 days. Besides, cytokines response was measured at 1, 3,7, and 14 days following Streptococcus iniae (S. iniae) infection after the feeding trial. All lipid profile parameters were nominally lowered, excluding high-density lipoprotein (HDL) that exhibited a significant increase in WS 5% group compared to other groups. Improved gut health integrity was observed, especially in WS 5% group in terms of increased goblet cell numbers, villous height, the width of lamina propria in all parts of the intestine, and a decrease in the diameter of the intestinal lumen of the distal intestine only. A significant down-regulation in the mRNA transcript level of cytokine genes (interleukin 1ß/IL-1ß, tumor necrosis factor α/TNFα, and interleukin 6/IL-6) was demonstrated in the kidney and spleen of WS-supplemented groups following S. iniae infection compared with the control infected (positive control/PC) group. Our findings give new insights for the potential roles of WS dietary inclusion not only on lipid profile and intestinal health integrity improvement in healthy fish under normal rearing but also as a prophylactic against the infection. Thus, WS can be incorporated as a promising nutraceutical in aquaculture.

Pharmaco-vigilance of oral MethylErgometrine prescriptions for delayed and secondary postpartum haemorrhage.

Objectives The objectives of this study were to quantify the prescription of oral methergin tablets in a busy Women's Hospital, assess the stated indications for such prescription and highlight the issues and safety profile of Methergin use especially in the postpartum patient. Methods Review of prescription data for oral Methergin and the corresponding annual figures on primary and secondary postpartum hemorrhage. Results Over a period of 5 years, oral Methergin prescriptions for delayed and secondary postpartum hemorrhage constituted less than 1% of the overall prescription in Obstetrics and Gynaecology, which ranged between 1214 and 2085 per year. The numbers were too few to ascertain any relationship with both types of postpartum hemorrhage. Although stated on the relevant Patient Information leaflet, no local or regional guideline on its use exist. Conclusions Specific and random trend monitoring of medications for continuing safety profile, risk benefit issues, or unapproved indication, may help in identifying, preventing and mitigating any medication safety matters. Clinical pharmacists in collaboration with physicians are well placed in conducting such pharmacovigilance activities to improve medication safety.

Incremental value of right parasternal transthoracic echocardiographic examination over the left parasternal approach in assessing ascending aorta size: Additional benefit of three-dimensional echocardiography.

BACKGROUND: The ascending aorta (AA) has not been well studied using two-dimensional right parasternal transthoracic echocardiographic examination (2DRPE). AIM: The aim of the present study was to assess the incremental value of 2DRPE over two-dimensional left parasternal transthoracic echocardiographic examination (2DLPE) in evaluating the size of AA in adult patients (pts) and, secondly, to determine whether live/real time three-dimensional (3D) RPE provided any additional benefit over 2DRPE. MATERIALS AND METHODS: The AA was successfully imaged by 2DLPE, 2DRPE, and 3D RPE in 87 of 141 (61.7%) pts which comprised of two groups of consecutive pts separated by an interval of 2 weeks. RESULTS: The maximum length of AA visualized by 2DRPE (4.98 ± 0.89) was larger than 2DLPE in 76/87(87%) pts (P < 0.001). Both the maximum systolic AA inner luminal width and leading edge-to-leading edge width by 2DRPE were greater than 2DLPE (P < 0.001). Similar to other noninvasive imaging modalities where mid-AA width is taken at level of right pulmonary artery, mid-AA width could also be taken at this level by 2DRPE in 79/87(91%) pts since this landmark was visualized during 2DRPE. However, this vessel could be visualized in only 2/87 (2%) pts with 2DLPE. 3DRPE conferred additional benefit over 2DRPE. The maximal AA length by 3DRPE was larger than 2DRPE in 60/87(69%) pts, and the maximal inner lumen and leading edge to leading edge widths were larger in 54/87(62%) and 66/87(76%) pts, respectively. CONCLUSION: Our preliminary study demonstrates significant incremental value of 2DRPE over 2DLPE in the assessment of AA. 3DRPE confers an additional advantage over 2DRPE.

Usefulness of right ventricular strain assessment in submassive pulmonary thromboembolism undergoing ultrasound-facilitated thrombolysis.

Massive and submassive pulmonary thromboembolism carry significant morbidity and mortality. We present an elderly female who was diagnosed with a submassive pulmonary embolism by computed tomographic angiography and treated with ultrasound-facilitated thrombolysis (UFT). This case demonstrates the usefulness of right ventricular longitudinal strain measurements by two-dimensional speckle tracking echocardiography in the evaluation of right ventricular function before and after UFT. Evaluation of right ventricle longitudinal strain by speckle tracking echocardiography may supplement other parameters in the assessment of right ventricular function in these patients.

Aqueous Stable Gold Nanostar/ZIF-8 Nanocomposites for Light-Triggered Release of Active Cargo Inside Living Cells.

A plasmonic core-shell gold nanostar/zeolitic-imidazolate-framework-8 (ZIF-8) nanocomposite was developed for the thermoplasmonic-driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF-8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule-release mechanism relies on the use of near-IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface-enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near-IR-triggered cargo release inside cells, thereby leading to DNA staining.

P2X7 receptor antagonism prevents IL-1ß release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy.

Salivary gland inflammation is a hallmark of Sjögren's syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated nonselective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1ß and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome. Here, our results show that in primary mouse submandibular gland (SMG) epithelial cells, P2X7R activation also induces the assembly of the NLRP3 inflammasome and the maturation and release of IL-1ß, a response that is absent in SMG cells isolated from mice deficient in P2X7Rs (P2X7R-/-). P2X7R-mediated IL-1ß release in SMG epithelial cells is dependent on transmembrane Na+ and/or K+ flux and the activation of heat shock protein 90 (HSP90), a protein required for the activation and stabilization of the NLRP3 inflammasome. Also, using the reactive oxygen species (ROS) scavengers N-acetyl cysteine and Mito-TEMPO, we determined that mitochondrial reactive oxygen species are required for P2X7R-mediated IL-1ß release. Lastly, in vivo administration of the P2X7R antagonist A438079 in the CD28-/-, IFNγ-/-, NOD.H-2h4 mouse model of salivary gland exocrinopathy ameliorated salivary gland inflammation and enhanced carbachol-induced saliva secretion. These findings demonstrate that P2X7R antagonism in vivo represents a promising therapeutic strategy to limit salivary gland inflammation and improve secretory function.

Laterally and Temporally Controlled Intracellular Staining by Light-Triggered Release of Encapsulated Fluorescent Markers.

Fluorescent molecular markers were encapsulated. The capsules were additionally modified with plasmonic nanoparticles. The encapsulated markers were endocytosed by cells. Upon light stimulation the plasmonic nanoparticles generated heat, which opened the encapsulation and transiently perforated the endosomal/lysosomal membrane surrounding the capsule, thus allowing for release of the marker into the cytosol. Fluorescence labeling of different intracellular compartments was demonstrated in this way. Most important, the cells do not need to be fixed and perforated, as the molecular markers are introduced into cells by endocytosis and subsequent light-induced release. Thus this technique allows for intracellular fluorescence labeling of living cells.

Clinical and immunological pattern and outcome of Egyptian systemic lupus erythematosus patients: a single center experience.

Objective The objective of this study was to describe the clinical and immunological pattern and disease outcome in Egyptian systemic lupus erythematosus patients. Patients and methods The medical records of 770 systemic lupus erythematosus patients who were followed from 2002-2015 at Kasr Alainy Hospital, Cairo University, were retrospectively reviewed. Results There were 707 (91.8%) females. The mean age at disease onset was 22.1 ± 8.6 and the disease duration was 6.1 ± 4.5 years. The main clinical manifestations were mucocutaneous (90.8% with oral ulcers affecting 52.5%), arthritis (80.3%), nephritis (67.8%), hematologic involvement (64.9%), serositis (55.2%) and neuropsychiatric manifestations (44.3%). The frequencies of antinuclear antibodies were 94.3%, anti-dsDNA 74.8%, anti-Smith 11%, anticardiolipin antibodies 29.5% and lupus anticoagulant 19.8%. Infections, predominantly bacterial, affected 337 (43.8%) patients. Thirty-three (4.3%) patients died. The main causes of death were sepsis and disease activity. The five- and 10-year survival rates for the total cohort were 97.4% and 96.3%, respectively, and were 96% and 92%, respectively for those with nephritis ( p = 0.008). Autoimmune hemolytic anemia, thrombocytopenia, elevated serum creatinine, a higher damage index, infections, a higher glucocorticoid dose and cyclophosphamide use ≥ six months were associated with an increased risk of mortality with odds ratios of 3.69, p < 0.01; 4.12, p < 0.001; 1.54, p < 0.001; 1.43, p < 0.001; 5.08, p < 0.001; 5.04, p < 0.001 and 2.25, p = 0.03, respectively. Conclusion Compared to other cohorts, a relatively lower mean age at systemic lupus erythematosus onset and higher frequencies of oral ulcers, serositis and nephritis were found.

Gold-Based Nanomaterials for Applications in Nanomedicine.

In this review, an overview of the current state-of-the-art of gold-based nanomaterials (Au NPs) in medical applications is given. The unique properties of Au NPs, such as their tunable size, shape, and surface characteristics, optical properties, biocompatibility, low cytotoxicity, high stability, and multifunctionality potential, among others, make them highly attractive in many aspects of medicine. First, the preparation methods for various Au NPs including functionalization strategies for selective targeting are summarized. Second, recent progresses on their applications, ranging from the diagnostics to therapeutics are highlighted. Finally, the rapidly growing and promising field of gold-based theranostic nano-platforms is discussed. Considering the great body of existing information and the high speed of its renewal, we chose in this review to generalize the data that have been accumulated during the past few years for the most promising directions in the use of Au NPs in current medical research.

Renal outcomes among Egyptian lupus nephritis patients: a retrospective analysis of 135 cases from a single centre.

OBJECTIVES: The objective of this paper is to describe renal outcomes in a group of Egyptian patients with lupus nephritis and to identify variable prognostic factors. PATIENTS AND METHODS: The records of 135 patients (129 females, six males) with biopsy-proven lupus nephritis seen between 1999 and 2011 at Kasr Al-Aini Hospital, Cairo University, were reviewed and included in a retrospective analysis. Biopsies were classified according to the WHO classification. Renal outcomes were defined according to the Renal Subcommittee of Renal Insufficiency of the American College of Rheumatology. RESULTS: The mean follow-up period was 55.64 ± 25.68 (range 4-156) months. Thirty-nine patients (29.9%) developed an adverse final outcome. This composite outcome, defined as persistent elevation of serum creatinine ≥ 1.2 mg/dl, chronic renal insufficiency, end-stage renal disease or death, was seen in 12 (8.9%), seven (5.2%), three (2.2%) and 17 (12.6%) patients, respectively. The overall patient survival was 93.5% and 87.5% at five and 10 years, respectively. Factors associated with an adverse outcome included male gender (p = 0.037), hypertension at nephritis onset (p = 0.001), serum creatinine ≥1.2 mg/dl (p < 0.001), urinary casts (p = 0.006), anticardiolipin antibodies (p = 0.03), class IV nephritis (p < 0.001), hyaline thrombosis (0.003), glomerular sclerosis (p = 0.002), tubular atrophy(p < 0.001), interstitial fibrosis (p < 0.001) and a higher chronicity index (p = 0.006). Time-dependent factors associated with an adverse outcome included failure to achieve remission within the first year, uncontrolled hypertension, persistently low C3 and development of flares (p = 0.003, < 0.001, = 0.004, = 0.003, respectively). CONCLUSION: The association of several adverse prognostic factors with the development of poor renal outcome has been confirmed in this study.

P2Y2 nucleotide receptor activation enhances the aggregation and self-organization of dispersed salivary epithelial cells.

Hyposalivation resulting from salivary gland dysfunction leads to poor oral health and greatly reduces the quality of life of patients. Current treatments for hyposalivation are limited. However, regenerative medicine to replace dysfunctional salivary glands represents a revolutionary approach. The ability of dispersed salivary epithelial cells or salivary gland-derived progenitor cells to self-organize into acinar-like spheres or branching structures that mimic the native tissue holds promise for cell-based reconstitution of a functional salivary gland. However, the mechanisms involved in salivary epithelial cell aggregation and tissue reconstitution are not fully understood. This study investigated the role of the P2Y2 nucleotide receptor (P2Y2R), a G protein-coupled receptor that is upregulated following salivary gland damage and disease, in salivary gland reconstitution. In vitro results with the rat parotid acinar Par-C10 cell line indicate that P2Y2R activation with the selective agonist UTP enhances the self-organization of dispersed salivary epithelial cells into acinar-like spheres. Other results indicate that the P2Y2R-mediated response is dependent on epidermal growth factor receptor activation via the metalloproteases ADAM10/ADAM17 or the α5ß1 integrin/Cdc42 signaling pathway, which leads to activation of the MAPKs JNK and ERK1/2. Ex vivo data using primary submandibular gland cells from wild-type and P2Y2R(-/-) mice confirmed that UTP-induced migratory responses required for acinar cell self-organization are mediated by the P2Y2R. Overall, this study suggests that the P2Y2R is a promising target for salivary gland reconstitution and identifies the involvement of two novel components of the P2Y2R signaling cascade in salivary epithelial cells, the α5ß1 integrin and the Rho GTPase Cdc42.

Non-Destructive Evaluation of the Physiochemical Properties of Milk Drink Flavored with Date Syrup Utilizing VIS-NIR Spectroscopy and ANN Analysis.

A milk drink flavored with date syrup produced at a lab scale level was evaluated. The production process of date syrup involves a sequence of essential unit operations, commencing with the extraction, filtration, and concentration processes from two cultivars: Sukkary and Khlass. Date syrup was then mixed with cow's and camel's milk at four percentages to form a nutritious, natural, sweet, and energy-rich milk drink. The sensory, physical, and chemical characteristics of the milk drinks flavored with date syrup were examined. The objective of this work was to measure the physiochemical properties of date fruits and milk drinks flavored with date syrup, and then to evaluate the physical properties of milk drinks utilizing non-destructive visible-near-infrared spectra (VIS-NIR). The study assessed the characteristics of the milk drink enhanced with date syrup by employing VIS-NIR spectra and utilizing a partial least-square regression (PLSR) and artificial neural network (ANN) analysis. The VIS-NIR spectra proved to be highly effective in estimating the physiochemical attributes of the flavored milk drink. The ANN model outperformed the PLSR model in this context. RMSECV is considered a more reliable indicator of a model's future predictive performance compared to RMSEC, and the R2 value ranged between 0.946 and 0.989. Consequently, non-destructive VIS-NIR technology demonstrates significant promise for accurately predicting and contributing to the entire production process of the product's properties examined.