From HIV to COVID-19, Molecular mechanisms of pathogens' trade-off and persistence in the community, potential targets for new drug development.

Background: On the staggering emergence of the Omicron variant, numerous questions arose about the evolution of virulence and transmissibility in microbes. Main body of the abstract: The trade-off hypothesis has long speculated the exchange of virulence for the sake of superior transmissibility in a wide array of pathogens. While this certainly applies to the case of the Omicron variant, along with influenza virus, various reports have been allocated for an array of pathogens such as human immunodeficiency virus (HIV), malaria, hepatitis B virus (HBV) and tuberculosis (TB). The latter abide to another form of trade-off, the invasion-persistence trade-off. In this study, we aim to explore the molecular mechanisms and mutations of different obligate intracellular pathogens that attenuated their more morbid characters, virulence in acute infections and invasion in chronic infections. Short conclusion: Recognizing the mutations that attenuate the most morbid characters of pathogens such as virulence or persistence can help in tailoring new therapies for such pathogens. Targeting macrophage tropism of HIV by carbohydrate-binding agents, or targeting the TMPRSS2 receptors to prevent pulmonary infiltrates of COVID-19 is an example of how important is to recognize such genetic mechanisms.

Biomarkers Regulated by Lipid-Soluble Vitamins in Glioblastoma.

Glioblastoma (GBM), a highly lethal form of adult malignant gliomas with little clinical advancement, raises the need for alternative therapeutic approaches. Lipid-soluble vitamins have gained attention in malignant brain tumors owing to their pleiotropic properties and their anti-cancer potential have been reported in a number of human GBM cell lines. The aim of this paper is to systematically review and describe the roles of various biomarkers regulated by lipid-soluble vitamins, such as vitamins A, D, E, and K, in the pathophysiology of GBM. Briefly, research articles published between 2005 and 2021 were systematically searched and selected from five databases (Scopus, PubMed, Ovid MEDLINE, EMBASE via Ovid, and Web of Science) based on the study's inclusion and exclusion criteria. In addition, a number of hand-searched research articles identified from Google Scholar were also included for the analysis. A total of 40 differentially expressed biomarkers were identified from the 19 eligible studies. The results from the analysis suggest that retinoids activate cell differentiation and suppress the biomarkers responsible for stemness in human GBM cells. Vitamin D appears to preferentially modulate several cell cycle biomarkers, while vitamin E derivatives seem to predominantly modulate biomarkers related to apoptosis. However, vitamin K1 did not appear to induce any significant changes to the Raf/MEK/ERK signaling or apoptotic pathways in human GBM cell lines. From the systematic analysis, 12 biomarkers were identified that may be of interest for further studies, as these were modulated by one or two of these lipid-soluble vitamins.

Yellow nail syndrome in an elderly sudanese female: A case report.

Yellow nail syndrome is a rare lymphatic abnormality without clear pathogenesis. Hereby, we report a 70-year-old Sudanese female patient who presented with recurrent cough, recurrent lower limb swelling, and yellowish nail discoloration diagnosed as yellow nail syndrome but unfortunately passed away due to acute respiratory distress syndrome (ARDS).

Compositional characteristics of dairy products and their potential nondairy applications after shelf-life.

Many dairy products are discarded and useless after end of shelf-life, which causes economic and environmental challenges. The objective of this study was to study the compositional characteristics of some dairy products before and after shelf-life, and develop a process to utilize those dairy products after end of shelf-life in non dairy applications (cosmetic cream and soap). Several dairy products, such as sterilized milk, yogurt, soft cheese, hard cheese, cream, and butter were collected from markets in Egypt before shelf-life and after three months of shelf-life. Electrophoresis analysis was conducted to estimate the changes in the protein fractions of protein products (sterilized milk, yogurt, and cheese) before and after expiration. Also, gas chromatography (GS) was performed to compare the fatty acids of fat products (cream and butter) before and after end of shelf-life. Sterilized milk, yogurt, soft, and hard cheese were turned into powder (Expired dairy products powder; EDPP) to be used as a raw material in manufacturing of cosmetic creams. The fat was separated from cream, butter, and hard cheese (Expired dairy products fat; EDPF) to be utilized in making soap. The formulated cosmetic creams were examined in vitro. Functional properties of cream were determined, such as appearance, spreadability, irritancy, and pH. Additionally, the soap quality was tested after manufacture. We found that dairy products, such as milk, yogurt, and cheese after shelf-life can be utilized as raw materials for the production of cosmetic creams, as well as production of soap from butter and cream. The produced products were similar to those in commercial markets. This study is an endeavor to conquer the dairy industry challenges, which are considered a huge loss from the economic and environmental aspects.

Design, synthesis and evaluation of new quinazolin-4-one derivatives as apoptotic enhancers and autophagy inhibitors with potent antitumor activity.

This work presents the design and synthesis of a series of new quinazolin-4-one derivatives, based on the established effectiveness of quinazoline-based small molecules as anticancer agents. Synthesized compounds were more potent against MCF-7 than A-549 with low to submicromolar IC50s. Compound 17 exhibited the best IC50 being equipotent with the positive control doxorubicin (IC50 = 0.06 µM) and better than 5-fluorouracil (IC50 = 2.13 µM). Compound 17 was further tested against MDA-MB-231 and MCF-10A and was found to be > 2 folds more cytotoxic on MCF-7. Significant apoptotic activity was elicited by 17 on MCF-7 where it increased apoptotic cell death along with induction of pre-G1 and G1-phase cell cycle arrest. Similarly, 17 was able to induce apoptosis in MD-MB-231 treated cells associated with a disruption of the cell cycle causing arrest at the pre-G1 and S phases. Investigation of gene expression in MCF-7 demonstrated an increased expression of the proapoptotic genes P53, PUMA, Bax, caspases 3, 8 and 9 and a decrease of the anti-apoptotic gene Bcl2. Also, 17 reduced autophagy giving way for apoptosis to induce cancer cells death. This latter observation was associated with downregulation of EGFR and its downstream effectors PI3K, AKT and mTor. As its biomolecular target, 17 also inhibited EGFR similar to erlotinib (IC50 = 0.072 and 0.087 µM, respectively). Additionally, in vivo testing in a mouse model of breast cancer affirmed the anti-tumor efficacy of 17. Finally, docking of 17 against EGFR ATP binding site demonstrated its ability to bind with EGFR resembling erlotinib.

Neurological manifestation of coeliac disease with particular emphasis on gluten ataxia and immunological injury: a review article.

Coeliac disease (CD) is a gluten-induced enteropathy affecting 1% of the population and has extra intestinal manifestations. One such expression involves nervous system, and CD may present as gluten ataxia (GA), peripheral neuropathy and epileptiform disorder among others. Considerable controversy exists on the exact pathophysiological mechanism of gluten leading to ataxia. It is, however, clear that in intestinal axis tissue transglutaminase 2 (tTG2) is the primary target but in the nervous system, tTG6 may be the causative antigen although its exact role is not clear. Furthermore, it has also been postulated that anti-gangliodise antibodies may play a role in the emergence of central pathology if not the key contender. Moreover, the association of neurological injury with non-coeliac gluten sensitivity (NCGS), a related but pathologically different condition implies an independent mechanism of neuronal injury by gluten in the absence of CD. This review will touch on the salient features of CD and the nervous system and will highlight current controversies in relation to gluten and GA.

In vitro and in vivo evaluation of taste-masked orodispersible tablets of fluoxetine hydrochloride for the treatment of depression.

AIM: Fluoxetine (FLX) has become the first-line drug in the pharmacotherapy of patients with depression. However, it has a strong unpleasant bitter taste, leading to the failure to complete the therapy. In this study, FLX is formulated into orodispersible tablets (ODTs) characterized by a fast release with an acceptable taste. METHOD: FLX ODTs were prepared by the complexation of FLX with ß-cyclodextrin (ß-CD) for taste-masking, using different super disintegrants, namely crospovidone (CP), croscarmellose sodium (Ccs), sodium starch glycolate (SSG), and indion. The FLX powder blend is estimated for pre-and post-compression parameters. The selected tablet formulations based upon drug release at 40 s with acceptable release patterns are investigated for accelerated stability testing and comparative in vivo study with a marketed product. RESULTS: It was found that all FLX-powder blends have good flow properties; all the prepared tablets complied with the pharmacopeial requirements for the unity of content, weight, friability, and hardness. Moreover, all the tablets obtained acceptable taste after complexation with ß-CD. The order of release of the drug, regarding super disintegrants used, was as in the following descending order: CP > Ccs > SSG > indion. Accelerated stability study of selected formulation F2 and F6 showed that; there were no considerable changes in physical properties, drug content, and percentage drug release. Furthermore, also the in vivo study proved the effectiveness of FLX ODTs as an antidepressant. CONCLUSION: The results obtained showed a promising potential of the prepared FLX ODTs for treating depression effectively.

Probiotic yogurt supplemented with nanopowdered eggshell: Shelf-life stability, physicochemical, and sensory characteristics.

The objectives of this study were to produce probiotic yogurt (5.0-7.0 log cfu/g) fortified with nanopowdered eggshell (NPES) at a rate of 0.02, 0.04, and 0.06 mg/ml, as well as, examine the effect of NPES on the physicochemical, microbial, sensory properties, and shelf-life of probiotic yogurt. The NPES was prepared by milling preboiled dried eggshell using a mortar grinder. The size of the milled powder was measured to assure that the diameter of the powder is 27 ± 1.7 nm. Yogurt was manufactured by dividing the pasteurized milk into four aliquots portions. The first portion was utilized as control (T1), while the other three portions were supplemented with 0.02 (T2), 0.04 (T3), and 0.06 (T4) mg/ml NPES. All treatments were inoculated with 5.11 log cfu of Lactobacillus delbruckii ssp. bulgaricus (Lb) and Streptococcus thermophilus (St) combined and 5 log cfu of Bifidobacterium bifidum (Bb) per kg of milk at 40°C until the pH of 4.6 was reached. The acidity, sensory properties, Bb count, total bacterial count (TBC), yeast, and mold counts were examined. The results showed that the acidity was increasing during storage, however, increasing NPES resulted in low acid development (p < .05). The shelf-life of control was ended after 8 d of storage at 4°C because molds were grown on the surface of the sample. The TBC significantly decreased (p < .05) as the concentration of NPES increased. Bb count in probiotic yogurt was also decreasing during storage. Yeast and molds were detected in control after 8 d; however, NPES did not result in molds even after 16 d of storage but yeast was exhibited. The NPES improved the sensory evaluation of probiotic yogurt slightly and increased the shelf-life of probiotic yogurt as compared to control.

Addition of inulin to probiotic yogurt: Viability of probiotic bacteria (Bifidobacterium bifidum) and sensory characteristics.

The objective of this work was to study the effect of different concentrations of inulin (0.2, 0.4, and 0.6%) on the viability of probiotic bacteria (Bifidobacterium bifidum) and sensory characteristics of probiotic yogurt. The yogurt was manufactured with Lactobacillus delbruckii ssp. bulgaricus (Lb), Streptococcus thermophilus (St), and Bifidobacterium bifidum (Bb). Raw milk was received, heated to 90°C, and divided into 4 aliquots portions. All portions were inoculated with 5.11 log cfu of Lb and St combined and 5 log cfu of Bb per kg of milk. The first portion was utilized as control (T1) while 0.2, 0.4, and 0.6% of inulin were added to the second (T2), third (T3), and fourth (T4) portions, respectively. All treatments were incubated at 40°C until a pH of 4.6 was reached. Subsequently, the yogurt was cooled and stored at 4°C for 16 days. Titratable acidity, total bacterial count (TBC), Bb count, yeast count, mold count, and sensory evaluation were determined during the storage. The results showed that the addition of inulin and the storage period have significant effects (p < .05) on the titratable acidity of the yogurt. The storage of control was ended after 8 days at 4°C due to the growth of molds on the surface of the samples. The TBC decreased (p < .05) over time in control from 8.28 to 7.97 log cfu/g. It was also decreased (p < .05) with increasing the concentration of inulin. However, the addition of inulin increased (p < .05) the viability of Bb during the storage, as well as, acted as an antimicrobial against molds in T2, T3, and T4. Additionally, there were no significant differences (p > .05) in the sensory evaluation of all treatments. We conclude that inulin can be utilized in the manufacturing of probiotic yogurt as a prebiotic, which, inturn, enhances the growth of Bb and increase the shelf-life.

Progressive ataxia and cognitive decline in a 67-year-old male: a diagnostic challenge.

We report the case of a 67-year-old male who presented with a six-week history of progressive unsteadiness, cognitive impairment and weight loss, in the context of a recent bereavement. Magnetic resonance imaging (MRI) performed several weeks earlier excluded acute stroke. Examination revealed gross bilateral ataxia, bradyphrenia and physical manifestations of depression. Collateral history suggested rapidly progressing symptoms over three months. Repeat MRI head showed features suggestive of Creutzfeldt-Jakob disease (CJD) including T2 hyperintensities in the basal ganglia. Cerebrospinal ˜fluid (CSF) samples were positive for 14-3-3 protein, S100b and real-time quaking-induced conversion (RT-QuIC) proteins confirming the diagnosis of sporadic CJD (sCJD).

Formulation and in vitro evaluation of a thermoreversible mucoadhesive nasal gel of itopride hydrochloride.

Itopride hydrochloride (ITO HCl) is a prokinetic agent, used in the treatment of gastrointestinal motility disorders. The aim of the study was to develop stable mucoadhesive thermoreversible nasal gel to avoid first pass effect. ITO HCl was incorporated into the blends of thermoreversible polymers like poloxamer 407 and various mucoadhesive polymers in different concentrations to increase the contact of the formulations with nasal mucosa. The compatibility between the drug and the suggested polymers was studied by Fourier transform infrared and differential scanning calorimetry (DSC). The formulations were evaluated for clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, and drug content. In addition, the in vitro drug release and the dissolution efficiency (DE)% were measured. The optimized formulations that showed the highest dissolution efficiency% (DE%) in saline phosphate buffer of pH 6.4 at 35 ± 0.5 °C were chosen for stability testing at temperatures of 4 ± 2 and 25 ± 2 °C/60 ± 5% RH. It was found that F1 and F17 that contain 18% w/v poloxamer 407 and 0.5% w/v of hydroxypropylmethyl cellulose K4M or methyl cellulose (MC), respectively, showed higher stability results as indicated by their higher t90 values (days).