Immunohistochemical Expression of MMR Proteins with Clinicopathological Correlation in Colorectal Cancer in Egypt

BACKGROUND: Microsatellite instability (MSI) is the genetic pathway underlying 15% of sporadic colorectal carcinoma (CRC) and hereditary non-polyposis CRC. MSI-H CRC has a distinct clinicopathological characteristic including excess mucin and signet ring component, proximal colon, Crohn’s like reaction, lymphocytic infiltration, and better survival. AIM: This research aims to screen Egyptian CRC patients for MSI status by IHC testing of expression of the MMR proteins in correlation to its clinicopathological features. MATERIAL AND METHODS: Immunohistochemistry study for mismatch repair proteins (MMR) was done on 115 cases of CRC. Their expressions were assessed and correlated to clinicopathological parameters in an attempt to obtain the most significant predictors of MSI. RESULTS: MSI (low and high) represents 67% of the study cases. The most frequent expression pattern was combined loss of MLH, and PMS2 (38% of MSI) followed by a combined loss of MSH2, and MSH6 (29% of MSI). There was significant correlation of expression pattern of MMR proteins with the laterality, lymphovascular emboli, perineural invasion, grade, T stage, N stage, signet ring component, tumor infiltrating lymphocyte, and peritumoral lesion (0.014, 0.035, 0.012, 0.033, 0.013, 0.000, 0.041, 0.012, and 0.009 respectively). Proximal location (right sided) and lower grade, higher nodal stage, and marked TIL were selected as predictors of MS-H CRC (0.005, 0.031, 0.025, and 0.000 respectively). CONCLUSION: All clinicopathological and histological parameters should be assessed in CRC for the sake of predicting MSI. The optimal approach to MSI evaluation is (IHC) assessment of MMR proteins

Synthesis of some Heterocyclic compounds bearing Coumarin nucleus and their Anti-inflammatory activity

Starting from 6-amino-4-methyl-2H-chromen-2-one 1, a series of some new heterocyclic compounds (2-14) incorporating coumarin moiety was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. The tested coumarin derivatives reduce the edema volume and serum levels of the pro inflammatory cytokines, IL-6 and TNF-α, and have effects on promoting production of anti-inflammatory cytokine, IL-10

The modulation effect of green tea and pumpkin oils on hyperlipidemia, oxidative stress, and hematological abnormalities in an experimental multiple sclerosis rat model

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory condition that can impair the body’s physiological functions. Although many diseases have been successfully treated with herbal treatments for a long time, the majority of the herbs utilized have unclear mechanisms. Therefore, this study aimed to examine the modulation effects of green tea oil (GTO) and pumpkin oil (PO) on hyperlipidemia, oxidative stress, and hematological abnormalities in an experimental multiple sclerosis rat model. Methods Forty albino male Wistar rats (weighing 120–140 g) were divided into four groups of six each: group 1, the control group; group 2, the myelin oligodendrocyte glycoprotein (MOG)-injected group; and groups 3 and 4, the MOG-injected groups treated with GTO and PO at 5 mg/kg b.w., respectively. At the end of the experiments, animals were anesthetized with diethyl ether inhalation, and blood samples were collected from the jugular vein. A Beckman Coulter was then used to determine the differential complete blood counts. The obtained serum was rapidly collected and stored at 20 °C to assess the lipid profile and oxidative stress and antioxidant biomarkers. Results Our findings showed that GTO and PO treatment produced a significant reduction in total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very low-density lipoprotein-cholesterol (VLDL-C) levels. Furthermore, GTO and PO treatment alleviated the elevated cardiovascular risk indices 1 and 2. Thiobarbituric acid reactive substance (TBARS) concentration significantly decreased and glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels significantly increased in rats injected with MOG and treated with GTO and PO. Furthermore, after GTO and PO treatment, the reduced red blood cells (RBCs) count, hemoglobin content (Hb%), lymphocyte percentage, and hematocrit (HCT) of MOG-injected rats increased, while the elevated white blood cells (WBCs), platelet, and neutrophil percentage substantially declined. Conclusion Collectively, our research revealed that GTO and PO may be capable of modulating hyperlipidemia, oxidative stress, and hematological abnormalities in the MS rat model

Improvement effects of green tea and pumpkin oils on myelin oligodendrocyte glycoprotein-induced Multiple sclerosis in rats

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) associated with significant progressive neurodegeneration. There is a lot of interest in the use of plant-based essential oils in traditional medicine to treat and prevent human illnesses, including MS. This research aimed to assess the neuroprotective effects of green tea oil (GTO) and pumpkin oil (PO) against myelin oligodendrocyte glycoprotein (MOG)-induced MS in Wistar rats as well as investigate the underlying molecular mechanisms. The Wistar rats were divided into four groups: group 1, normal control; group 2, MOG-injected; and groups 3 and 4, MOG-injected groups treated with 5 ml/kg body weight each of GTO and PO, respectively. The chemical profiles of components within a GTO and PO were identified using gas chromatography-mass spectrometry (GC–MS). Treatment with GTO and PO substantially improved the decreased dopamine, serotonin, norepinephrine, and acetylcholine levels in the brain of the MOG-injected rats. It also suppressed the elevated epinephrine levels. The histological injuries in the brain cortical tissue of the MOG-injected group were notably improved after supplementing with GTO and PO. Furthermore, brain lipid peroxidation and serum INF-β concentration were significantly lower in the MOG-injected rats treated with GTO and PO. The brain GSH, SOD, GPx, as well as serum coenzyme Q10, and α-tocopherol levels were significantly enhanced by GTO and PO supplementaion. Additionally, GTO and PO administration into MOG-injected rats significantly upregulated Nrf2, Bcl-2, and PCNA while significantly downregulated TNF-α, NF-κB, iNOS, p53, and Bax expression levels. Taken together, these findings suggest that GTO and PO efficiently ameliorate MOG-induced MS via enhancing the antioxidant, anti-inflammatory, and anti-apoptotic effects

Prognostic Value of BRAF, Programmed Cell Death 1 (PD1), and PD Ligand 1 (PDL1) Protein Expression in Colon Adenocarcinoma

Patients with colorectal cancer in different stages show variable outcomes/therapeutic responses due to their distinct tumoral biomarkers and biological features. In this sense, this study aimed to explore the prognostic utility of BRAF, programmed death-1 (PD1), and its ligand (PDL1) protein signatures in colon adenocarcinoma. The selected protein markers were explored in 64 archived primary colon adenocarcinomas in relation to clinicopathological features. BRAF overexpression was found in 39% of the cases and was significantly associated with grade 3, N1, advanced Dukes stage, presence of relapse, and shorter overall survival (OS). PD1 expression in the infiltrating immune cells (IICs) exhibited significant association with T2/T3, N0/M0, early Dukes stage, and absence of relapse. PDL1 expression in IICs is significantly associated with advanced nodal stage/distant metastasis, advanced Dukes stage, and shorter OS. Meanwhile, PDL1 expression in neoplastic cells (NC) was associated with the advanced lymph node/Dukes stage. A positive combined expression pattern of PDL1 in NC/IICs was associated with poor prognostic indices. Tumor PDL1 expression can be an independent predictor of OS and DFS. The multivariate analyses revealed that short OS was independently associated with the RT side location of the tumor, PD1 expression in stromal IICs, and PDL1 expression in NC. In conclusion, overexpression of BRAF in colon adenocarcinoma is considered a poor prognostic pathological marker. In addition, PDL1 expression in NC is considered an independent prognostic factor for DFS/OS. Combined immunohistochemical assessment for BRAF and PD1/PDL1 protein expressions in colon adenocarcinoma might be beneficial for selecting patients for future targeted therapy

Evaluation of inactivated avian influenza virus and Newcastle disease virus bivalent vaccination program against newly circulated H5N8 and NDV strains

ABSTRACT: Avian influenza virus (AIV) and Newcastle disease virus (NDV) are respiratory illness syndromes that have recently been detected in vaccinated flocks and are causing major financial losses in the chicken farming industry. The objective was to evaluate the efficacy of Valley Vac H5Plus NDVg7 vaccine in protecting chickens against the H5N8 and NDV strains that have recently been circulating in comparison with the efficacy of the commercially available bivalent H5+ND7 vaccine. In contrast to the H5+ND7 vaccine, which was made of genetically distinct H5N8/2018 clade 2.3.4.4b genotype group (G5), H9N2/2016, H5N1/2017, and genetically comparable NDV genotype VII 1.1/2019 of the recently circulating challenge viruses, the Valley Vac H5Plus NDVg7 vaccine consisted of the recently isolated (RG HPAI H5N1 AIV/2015 Clade 2.2.1.2, RG HPAIV H5N8/2020 Clade 2.3.4.4b genotype group 6 (G6), and NDV genotype VII 1.1/2012) which were genetically similar to challenged strains. To determine the effectiveness of the Valley Vac H5Plus NDVg7 vaccine, a total of 70-day-old commercial chicks were divided into 7 groups of 10 birds each. Groups (G1 and G4) received Valley Vac H5Plus NDVg7 vaccine. Groups (G2 and G5) groups received commercial H5+ND7 vaccine. While groups (G3 and G6) were kept nonvaccinated, and group (G7) was kept as a nonchallenged and nonvaccinated. After 3-wk post vaccination (WPV), groups G1, G2, and G3 were challenged with A/Duck/ Egypt/SMG4/2019(H5N8) genotype G6. On the other hand, groups G4, G5, G6 were challenged with NDV/EGYPT/18629F/2018 genotype VII 1.1 with an intranasal injection of 0.1 mL. Antibody titer was calculated at the first 3 wk after vaccination, and the viral shedding titer was calculated at 3-, 5-, and 7-days post challenge. Mortality and morbidity rates were monitored daily during the experiment, and for the first 10 d after the challenge, to provide an estimate of the protection rate. The results showed that a single dosage of 0.5 mL per bird of Valley Vac H5Plus NDVg7 vaccine provides 80% protection against both H5N8 and NDV, compared to the bivalent H5+ND7 vaccine, which provided 20 and 80% protection against H5N8 and NDV, respectively. In addition, 0.5 mL per bird of Valley Vac H5Plus NDVg7 vaccine produced a greater immune response against both viruses than commercial vaccination at 1 to 3 WPV with a significant difference at 1 WPV for H5N8 and a comparatively higher immune response for NDV. Furthermore, it reduced virus shedding of H5N8 on the third, fifth, seventh, and tenth days lower than H5+ND7 vaccine with a significant difference on the third day for H5N8 and relatively lower than bivalent H5+ND7 vaccine for NDV with a significant difference on the fifth day. The Valley vaccinated group demonstrated more tissue intactness compared to the commercially vaccinated group against the H5N8 challenge, however the bivalent commercially vaccinated group showed the similar level of tissue integrity against NDV. In conclusion, Valley Vac H5Plus NDVg7  that contains the  genetically similar strain to recently circulating challenged virus (H5N8 genotype G6) provided better protection with greater immune response and decreased the amount of virus shed against H5N8 genotype G6 and showed less histopathological alteration than the commercial bivalent H5+ND7 vaccine that contain genetically distinct (H5N8 genotype G5). However the Valley Vac H5Plus NDVg7 provided the same protection with relatively high immune response and  relatively decreased the amount of virus shed and showed equal tissue integrity than the commercial bivalent H5+ND7 vaccine against NDV genotype VII 1.1 that contain the same genotype of NDV genotype VII 1.1

Immunogenicity and Cross-Protective Efficacy Induced by an Inactivated Recombinant Avian Influenza A/H5N1 (Clade 2.3.4.4b) Vaccine against Co-Circulating Influenza A/H5Nx Viruses

Controlling avian influenza viruses (AIVs) is mainly based on culling of the infected bird flocks or via the implementation of inactivated vaccines in countries where AIVs are considered to be endemic. Over the last decade, several avian influenza virus subtypes, including highly pathogenic avian influenza (HPAI) H5N1 clade 2.2.1.2, H5N8 clade 2.3.4.4b and the recent H5N1 clade 2.3.4.4b, have been reported among poultry populations in Egypt. This demanded the utilization of a nationwide routine vaccination program in the poultry sector. Antigenic differences between available avian influenza vaccines and the currently circulating H5Nx strains were reported, calling for an updated vaccine for homogenous strains. In this study, three H5Nx vaccines were generated by utilizing the reverse genetic system: rgH5N1_2.3.4.4, rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2. Further, the immunogenicity and the cross-reactivity of the generated inactivated vaccines were assessed in the chicken model against a panel of homologous and heterologous H5Nx HPAIVs. Interestingly, the rgH5N1_2.3.4.4 induced high immunogenicity in specific-pathogen-free (SPF) chicken and could efficiently protect immunized chickens against challenge infection with HPAIV H5N1_2.3.4.4, H5N8_2.3.4.4 and H5N1_2.2.1.2. In parallel, the rgH5N1_2.2.1.2 could partially protect SPF chickens against infection with HPAIV H5N1_2.3.4.4 and H5N8_2.3.4.4. Conversely, the raised antibodies to rgH5N1_2.3.4.4 could provide full protection against HPAIV H5N1_2.3.4.4 and HPAIV H5N8_2.3.4.4, and partial protection (60%) against HPAIV H5N1_2.2.1.2. Compared to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2 vaccines, chickens vaccinated with rgH5N1_2.3.4.4 showed lower viral shedding following challenge infection with the predefined HPAIVs. These data emphasize the superior immunogenicity and cross-protective efficacy of the rgH5N1_2.3.4.4 in comparison to rgH5N8_2.3.4.4 and rgH5N1_2.2.1.2

Impacts of turmeric and its principal bioactive curcumin on human health: pharmaceutical, medicinal, and food applications : a comprehensive review

The yellow polyphenolic pigment known as curcumin, originating from the rhizome of the turmeric plant Curcuma longa L., has been utilized for ages in ancient medicine, as well as in cooking and food coloring. Recently, the biological activities of turmeric and curcumin have been thoroughly investigated. The studies mainly focused on their antioxidant, antitumor, anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective impacts. This review seeks to provide an in-depth, detailed discussion of curcumin usage within the food processing industries and its effect on health support and disease prevention. Curcumin’s bioavailability, bio-efficacy, and bio-safety characteristics, as well as its side effects and quality standards, are also discussed. Finally, curcumin’s multifaceted uses, food appeal enhancement, agro-industrial techniques counteracting its instability and low bioavailability, nanotechnology and focused drug delivery systems to increase its bioavailability, and prospective clinical use tactics are all discussed