Clinical, biochemical, and molecular characterization of mucopolysaccharidosis type III in 34 Egyptian patients.

Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disorder characterized by progressive neurocognitive deterioration. There are four MPS III subtypes (A, B, C, and D) that are clinically indistinguishable with variable rates of progression. A retrospective analysis was carried out on 34 patients with MPS III types at Cairo University Children's Hospital. We described the clinical, biochemical, and molecular spectrum of MPS III patients. Of 34 patients, 22 patients had MPS IIIB, 7/34 had MPS IIIC, 4/34 had MPS IIIA, and only 1 had MPS IIID. All patients presented with developmental delay/intellectual disability, and speech delay. Ataxia was reported in a patient with MPS IIIC, and cerebellar atrophy in a patient with MPS IIIA. We reported 25 variants in the 4 MPS III genes, 11 of which were not previously reported. This is the first study to analyze the clinical and genetic spectrum of MPS III patients in Egypt. This study explores the genetic map of MPS III in the Egyptian population. It will pave the way for a national registry for rare diseases in Egypt, a country with a high rate of consanguineous marriage and consequently a high rate of autosomal recessive disorders.

Enhancing the antioxidant properties of functional herbal beverages using Ultrasonic-Assisted extraction: Optimized formulation and synergistic combinations of taurine and vit. C.

Functional herbal beverages are gaining popularity in the beverage industry due to their natural antioxidants. However, the high concentration of antioxidants in these beverages can lead to increased toxicity, limiting their use. Moreover, the composition of tap water, including mineral salts and hydrogen carbonate ions, hampers the extraction process of polyphenolic compounds, thereby reducing the antioxidant properties. This study aims to address these challenges by enhancing antioxidant properties, reducing toxic effects, and improving the extraction process. Low-dose herbal extracts of green tea, rosemary, milk thistle, and sage were extracted using 100 ml of boiling water as a solvent, with ultrasonication employed for 20 min. Taurine, vit. C, and their combination were added to the extracts. The antioxidant properties, polyphenol, and flavonoid content were evaluated. The results demonstrated that the low-dose herbal tea combined with taurine and vit. C exhibited higher antioxidant activity compared to high-dose tea. Notably, the combination of taurine and vit. C showed the strongest synergistic effect. The addition of vit. C to these combinations eliminated any antagonism and resulted in a robust synergistic effect. The optimal conditions for enhancing antioxidant properties were determined as follows: an herbal type of 0.030 ≈ 0 (sage), vit. C concentration of 0.045 g/100 ml, and taurine concentration of 0.179 g/100 ml. The measured responses for reducing power, DPPH, and ABTS were 0.152 µg vit. C equivalent/ml, 67.778 %, and 87.630 %, respectively. This study provides valuable insights into optimizing the antioxidant properties of herbal beverages through the synergistic combinations of taurine and vit. C. By employing proper preparation techniques and including taurine and vit. C, the antioxidant capacity of these beverages can be significantly improved, potentially offering health benefits against degenerative diseases.

Development of a functional cake with probiotics and micro-encapsulated essential oils: Evaluation of nutritional properties, liver protection, and immune boosting.

This study used probiotics and micro-encapsulated clove and cinnamon oils to develop a functional cream-stuffed cake based on sweet potatoes flour and rice flour instead of wheat flour. The cake was evaluated for its physical, chemical, and sensory properties and its antioxidant capacity. The protective effect of the cake against liver injury and immunosuppression induced by thioacetamide injection in male rats was also evaluated. The study found that eugenol and cinnamaldehyde were the majority of volatile compounds in the essential oils used in the cake, with values of 78.73 % and 81.57 %, respectively, as determined by GC-MS analysis. The viable counts of added probiotics in the cake ranged from 13.15 to 11.21 log CFU/g and were still above the threshold for health benefits. The cake had an increased dietary fiber and protein content while containing a low-fat percentage compared to a commercial cake sample. The innovative cake also contained higher levels of water-soluble and fat-soluble vitamins and minerals such as iron, calcium, potassium, and zinc. The antioxidant capacity of the cake was evaluated, and it was found to contain 1827.23 mg GAE/100 g of total phenols and 97.13 mg QE/100 g of flavonoids. The cake was also found to have antioxidant activity and was effective in protecting the liver from oxidative stress and inflammation and reducing immunodeficiency associated with liver damage.

Ameliorative effects of vitamins-loaded flavoured nanophytosomes fortified with star anise volatile oil against CsA-Induced liver and kidney injury in rats: Application in functional ice cream.

This study investigated the effect of flavoured nanophytosomes loaded with vitamins A, E, D, B complex, folic acid, and C, as well as zinc on the immunosuppressive cyclosporin A (CsA)-induced liver and kidney injury in male rats. The vitamins flavoured nanophytosomes (VFnPs) were characterized in terms of particle size, zeta potential, encapsulation efficiency. Ice cream was flavoured with star anise volatile oil to mask the VFnPs' flavour and unacceptable taste. The study found that treatment with CsA alone resulted in increased (P > 0.05) levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, while the levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1ß, and TLR4 decreased (P > 0.05). However, the group that received CsA simultaneously with VFnPs showed a significant (P > 0.05) decrease in the levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, and increased (P > 0.05) levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1ß, and TLR4. The increase in the ratio of VFnPs had little effect on the physiochemical and sensory evaluation of the ice cream. Finally, the study suggests that VFnPs could potentially protect against CsA-induced liver and kidney injury and serve as a promising natural therapy for treating such conditions.

Production of natural flavor compounds using Bacillus subtilis-fermented soybean meal extract and their biological potential: a comprehensive in vitro study.

This study aims to investigate the production of natural flavor compounds through the utilization of Bacillus subtilis-fermented soybean meal extract and evaluate their biological potential. The experiment involved a comprehensive in vitro investigation to assess the capabilities and effects of the produced flavor compounds. The resulting flavor compounds were subjected to various in vitro tests to assess their properties, including cytotoxicity, antioxidant activity, anticancer potential, antiviral activity, and antimicrobial activity. To enhance the fermentation process, soybean meal extract was fortified with a combination of L-Lysine and L-Threonine. Gas chromatography-mass spectrometry (GC/MS) analysis was conducted on the fermented soybean meal using two strains of Bacillus subtilis, namely NRCH123 and NRCZ144. This analysis revealed the presence of various volatile compounds in all extracts, including Butylated hydroxytoluene. The fermented soybean extract with bacillus subtilis NRCZ144 (B2) fortified with a combination of 2.5% (w/w) L-Lysine and 2.5% w/w L-threonine (SLT2) exhibited a rich profile of flavor compounds, with Eucalyptol being identified as the predominant compound. The antioxidant activity of the SLT2 extract was found to be 72.04% at a concentration of 100 µg/mL, indicating significant antioxidant potential. Furthermore, when tested against the human liver cancer cell line HepG2, the extract demonstrated anticancer activity with an IC50 value of 2.26 µg/mL. The extract exhibited potent cytotoxicity, with an IC50 value of 1.02 µg/mL. Importantly, the SLT2 extract displayed strong antibacterial and antifungal activity, even at very low concentrations. The extract's antimicrobial properties indicate its potential for inhibiting the growth of bacteria and fungi.

Clinical and genetic spectrum of mitochondrial DNA depletion syndromes: A report of 6 cases with 4 novel variants.

Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a heterogeneous group of rare autosomal recessive genetic disorders characterized by a decrease in the number of mtDNA copies inside the organ involved. There are three distinct forms of MDS including the hepatocerebral, the myopathic and the encephalomyopathic forms. The diversity in the clinical and genetic spectrum of these disorders makes the diagnosis challenging. Here, we describe the clinical phenotype and the genetic spectrum of 6 patients with MDS including 4 novel variants and compare them with previously reported cases. SUBJECT AND METHODS: Six patients from six unrelated families were included in this study. All the patients were subjected to a detailed history, thorough general and neurologic examination, basic laboratory investigations including lactic acid and ammonia, amino acids, acylcarnitine profiles and brain MRI. Whole-exome sequencing was performed for all of them to confirm the suspicion of mitochondrial disorder. RESULTS: In our series, four patients presented with the hepatocerebral form of MDS with the major presenting manifestation of progressive liver cell failure with severe hypotonia and global developmental delay. Four variants in the DGUOK gene and the MPV17 have been identified including 2 novel variants. One patient was identified in the myopathic form presenting with myopathy associated with two novel variants in the TK2 gene. One patient was diagnosed with encephalomyopathic form presenting with persistent lactic acidosis and global delay due to a homozygous variant in the FBXL4 gene. CONCLUSION: MDS has a wide spectrum of heterogeneous clinical presentations and about nine different genes involved. Whole exome sequencing (WES) has resulted in faster diagnosis of these challenging cases as the phenotype overlap with many other disorders. This should be considered the first-tier diagnostic test obviating the need for more invasive testing like muscle biopsies.

Genotype-phenotype associations in familial Mediterranean fever: a study of 500 Egyptian pediatric patients.

INTRODUCTION: Familial Mediterranean fever (FMF) is the most prevalent monogenic autoinflammatory disease, caused by recessively inherited MEFV gene mutations. The most frequent MEFV mutations differ in penetrance and disease severity. We investigated the genotype-phenotype associations of the three most frequent MEFV gene mutations (M680I, M694V, and V726A) in Egyptian FMF children, regarding clinical features, severity, and colchicine response. METHODS: We conducted a retrospective analysis of the medical registries of 500 FMF pediatric patients from Metropolitan Cairo between 2010 and 2015. The diagnosis was based on the Tel-Hashomer clinical diagnostic criteria. Clinical data and baseline investigations were collected. Mutation analysis was performed by the amplification-refractory mutation system (ARMS)-PCR method. RESULTS: Males represented 54% and ages ranged from 2 to 18 years. The most frequent symptoms were abdominal pain, fever, and arthralgia. Clinical features mostly associated with M694V mutation either homozygous or heterozygous whether simple, double, or triple. Of the patients, 94.6% completely responded to colchicine. Among patients benefiting from colchicine, 42.5% had M694V/V726A, 21.6% had M694V/V726A/M680I, and 21.1% had M694V genotype. Simple heterozygous M694V or V726A mutations conveyed a moderate phenotype in 57.1% and 50% of cases, respectively. Homozygous M694V mutation showed moderate and severe phenotypes in 21.7% and 65.2% of cases, respectively. Compound M694V/V726A mutation associated with moderate or severe disease in 48.3% and 33.8% of cases, respectively. CONCLUSION: This study encompasses the largest group of Egyptian pediatric FMF up to date to explore their genotype-phenotype associations. Our results support the notion that the genotype influences the phenotype as regards clinical manifestations, disease severity, and colchicine response. KEY POINTS: • This study encompasses the largest group of Egyptian pediatric patients affected by FMF up to date to explore their genotype-phenotype associations. • Our results support the notion that the genotype influences the phenotype as regards the clinical manifestations, the disease severity, and the response to colchicine treatment.

A comparative study on flavour components and therapeutic properties of unfermented and fermented defatted soybean meal extract.

Microbial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography-mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and δ-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362 ± 0.05 and 2.11 ± 0.02 mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763 ± 0.05 and 3.795 ± 0.03 mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331 ± 0.04 and 3.971 ± 0.02 mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 µg/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1 mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1 mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.