Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Evaluation of the role of EGFR exon 19 747-750 deletion mutation and plasma amino acid profile in the development of lung cancer.

BACKGROUND: Lung cancer (LC) is the most common form of cancer in the world. Of the proteins involved in cell differentiation and proliferation, the epidermal growth factor receptor (EGFR) is among the most significant. Amino acids play a crucial role in cell physiology as metabolic regulators. The benefits of liquid biopsies are their non-invasive nature, ease of collection, and ability to depict the entire tumor's status. The present study is designed to detect the relation between the EGFR exon 19 747-750 deletion mutation and lung cancer and investigate the patterns of alterations of plasma-free amino acids (PFAA) in lung cancer patients of different histopathological types and stages as biomarkers for early detection of lung cancer. METHODS: The study sample comprised 60 lung cancer patients and 60 age- and sex-matched healthy individuals as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the EGFR exon 19 747-750 deletion mutation, and an AA analyzer was used to quantify the plasma free amino acid (PFAA) profile. RESULTS: Compared with controls, LC patients had significantly higher levels of three AAs and significantly lower levels of fifteen AAs. Thirteen AAs varied significantly between stages I and II. In the lung cancer group, the percentage of cases of mutant EGFR exon-19 deletion increased to 30% from 13.3% in the control group. The histological forms of lung cancer did not significantly differ in this rise. Valine and citrulline plasma levels were substantially greater in the mutant than in the wild-type. Lysine, histidine, and methionine were the independent predictors of the LC group in multivariate analysis. CONCLUSION: Lung cancer development is influenced by the EGFR exon 19 747-750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations.

Acetylated oligopeptide and N-acetylcysteine protect against iron overload-induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO-1 and downregulation of MMP-9/TIMP-1 and GFAP.

Iron accumulation in the brain causes oxidative stress, blood-brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron-induced hippocampal damage compared to N-acetyl cysteine (NAC). This 5-week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme-linked immunosorbent assay, spectrophotometry, and qRT-PCR were used to measure MMP-9, tissue inhibitor metalloproteinase-1 (TIMP-1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP-9, TIMP-1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO-1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload-induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.

Does interleukin-33 level correlate with the activity of Pemphigus vulgaris?: A case-control study.

Pemphigus is a group of immune-mediated blistering diseases of skin and mucus membrane caused by destruction of the intercellular junction (desmosomes) by autoantibodies. Pemphigus vulgaris (PV) is considered the most common type of all pemphigus family. Various cytokines play a major role in pemphigus pathogenesis. Interleukin-33 (IL-33) role has been studied in various autoimmune diseases as; psoriasis and rheumatoid arthritis, yet it has not been studied in Egyptian patients with PV. The study aimed to evaluate the possible role of IL-33 in PV by assessing its level in the serum using ELISA and to detect its correlation with activity score using Pemphigus Disease Area Index (PDAI). Forty-four patients with PV and 36 age and sex-matched healthy controls were enrolled in the study. After full history taking and complete dermatological examination, the severity score was calculated using PDAI, then serum samples were taken from each patient and control subjects and subjected to quantitative measurement of serum IL-33 using ELISA. Serum level of IL-33 is significantly raised in PV patients compared to control subjects (P-value = .007). The level of IL-33 was found to be strongly correlated with the activity of the disease measured by PDAI. IL-33 might have a role in PV pathogenesis as shown by its rising level in PV patients. In addition, serum level of IL-33 is strongly correlated with the activity of PV. Thus, we suspect that IL-33 can be used as marker for monitoring PV severity and measuring treatment efficacy.

Acetylated Oligopeptide and N-acetyl cysteine Protected Against Oxidative Stress, Inflammation, Testicular-Blood Barrier Damage, and Testicular Cell Death in Iron-Overload Rat Model.

Multiple organs, including the testes, are damaged by iron overload. It has been shown that N-acetyl cysteine (NAC) influences oxidative stress in iron overload. The present study aimed to evaluate the roles of acetylated peptide (AOP) and NAC in the inhibition of iron-overload induced-testicular damage. At the beginning of the experiment, NAC (150 mg /kg) was given for a week to all 40 rats. Then, four groups were formed by dividing the animals (10 rats/group). Group I included healthy control rats. Group II (iron overload) was given intraperitoneal iron dextran (60 mg/kg/day) 5 days a week for 4 weeks. Group III (NAC) was given NAC orally at a dose of 150 mg/kg/day for 4 weeks in addition to iron dextran. Group IV (AOP) was given AOP orally at a dose of 150 mg/kg/day for 4 weeks besides iron dextran. When the experiment time was over, testosterone serum level, testicular B cell lymphoma-2 (BCL-2) and protein kinase B (PKB) protein levels, nuclear factor kappa-B (NF-κB), and Beclin1 mRNA expression levels, and malondialdehyde (MDA), and reduced glutathione (GSH) were determined by ELISA, quantitative reverse transcription-PCR, and chemical methods. Finally, histopathological examinations and immunohistochemical detection of claudin-1 and CD68 were performed. The iron overload group exhibited decreased testosterone, BCL-2, PKB, claudin-1, and GSH and increased MDA, NF-κB, Beclin1, and CD68, while both NAC and AOP treatments protected against the biochemical and histopathological disturbances occurring in the iron overload model. We concluded that NAC and AOP can protect against testes damage by iron overload via their antioxidant, anti-inflammatory, antiapoptotic, and ant-autophagic properties. The NAC and AOP may be used as preventative measures against iron overload-induced testicular damage.

Impact of porous microsponges in minimizing myotoxic side effects of simvastatin.

Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m2/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.

Significant Interrelations among Serum Annexin A1, Soluble Receptor for Advanced Glycation End Products (sRAGE) and rs2070600 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of death and morbidity; it may be accompanied by oxidative stress and inflammation with or without underlying genetic etiology. Finding circulating biomarkers for COPD that can help early diagnosis and predict exacerbation and association with respiratory functions has been challenging. There were 40 healthy participants and 60 COPD patients in this research. The rs2070600 gene variant was examined by PCR-RFLP. Circulating sRAGE and annexin A1 levels were determined by ELISA. GSH and MDA were determined by spectrophotometry. In COPD patients, sRAGE serum levels were substantially lower, but conversely, annexin A1 levels were much greater than in controls. The rs2070600 gene polymorphism's strong association with COPD was demonstrated by genotyping and allelic frequency distribution. The GA genotype was most distributed in COPD, and it was strongly linked to lower serum sRAGE levels. The interrelation between annexin A1, sRAGE, and COPD could be explained through effects on inflammatory mediators' pathways. The rs2070600 gene polymorphism was found to significantly enhance the risk of COPD. Serum sRAGE and annexin A1 may be considered potential diagnostic tools for COPD. Through impacts on GSH and MDA levels that alter the release of inflammatory factors and, therefore, lung damage, it is possible to explain the relationship between annexin A1, sRAGE, and COPD.

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression.

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.

Association of Treg and TH17 Cytokines with HCV Pathogenesis and Liver Pathology.

Chronic hepatitis C (CHC) infection is considered a high risk for development of end-stage liver diseases, particularly server hepatitis, decompensated liver cirrhosis, and hepatocellular carcinoma. Regulatory T cells (Treg) and T-helper 17 (TH17) associated cytokines presumed to play a pivotal role in the immune pathogenesis of HCV infection and stimulate autoimmune diseases. Herein, we tried to assess the association of Treg and TH 17 cytokines with HCV pathogenesis and liver pathology. Fifty CHC infected patients and twenty HCV free controls were included in this study, IL17, IL21, IL10, IL4, TGF- and IL35 serum levels were assessed in both groups using enzyme linked immunosorbent assay (ELISA). CHC infected patients had statistically significant higher values of all serum cytokine levels when compared to the control group (P < 0.0001) for each. Additionally, serum levels of IL17, IL10 and IL35 were positively correlated with viral load. Also, the serum level of IL17 IL21, IL10 and IL35 was positively correlated with ALT serum levels. Only IL21 and IL10 were positively correlated with AST levels. Serum IL17, IL10, TGF- and IL35 levels were significantly elevated in CHC patients with advanced fibrosis stages. We concluded that CHC infected patients displayed high serum levels of Treg and TH17 associated cytokines. Collectively, these results support the hypothesis that liver damage in CHC infection might be due to an immune-mediated destructive mechanism rather than to the direct cytopathic effect of the virus itself.

The adipokine Chemerin and Fetuin-A Serum Levels in Type 2 Diabetes Mellitus: Relation to Obesity and Inflammatory Markers.

Chemerin and fetuin-A are recently discovered as metabolic regulator hormone in obesity and type 2 diabetes mellitus. However, elevated levels of chemerin and fetuin-A have been associated with insulin resistance and systemic inflammation. The present study aimed to investigate the significance of serum chemerin and fetuin-A levels in obese diabetic patients. Also, to determine whether, chemerin and fetuin-A along with markers of inflammation (IL6 and CRP) and obesity-related parameters in T2DM patients. Serum levels of chemerin and fetuin-A were evaluated using ELISA in 71 T2DM patients and 14 apparently healthy controls. Both groups were subdivided into obese and lean. Serum chemerin and fetuin-A levels were significantly higher in T2DM patients compared to controls (P < 0.001, for both) and significantly higher in obese T2DM in comparison to obese control group (P < 0.01 & P < 0.05, respectively). Serum chemerin and fetuin-A levels correlated positively with HbA1c, HOMA-IR, FBG, IL6 and CRP. In obese patients, serum chemerin and fetuin-A levels correlated positively with BMI and waist circumference. In conclusion, the strong association of chemerin and fetuin-A with insulin resistance and some inflammatory markers may provide an interesting link between obesity, inflammation and diabetes mellitus in human.