A stability indicating RP-HPLC-UV assay method for the simultaneous determination of hydroquinone, tretinoin, hydrocortisone, butylated hydroxytoluene and parabens in pharmaceutical creams.

Multicomponent drugs are medications that combine two or more active pharmaceutical ingredients in a single dosage form. These dosage forms improve the patient compliance, reduce the risk of drug interactions, and simplify dosing regimens. However, quality control of these multicomponent dosage forms can be challenging, especially if the final product contains four or more ingredients that are active (comprise stabilizers, preservatives, excipients, and other components). This problem can be more pronounced if the excipients can interfere with the analysis. In this work, a stability indicating assay method was developed and validated (according to the ICH International Guidelines) for the simultaneous determination of hydroquinone (HQ), tretinoin (TRT), hydrocortisone (HCA), butylated hydroxytoluene (BHT), methyl paraben (MP) and propyl paraben (PP) in commercially available pharmaceutical creams. The proposed method is based on gradient elution using X-Bridge C18 (150 × 4.6 mm, 5 µm) column with a flow rate of 1 mL/min. The linear ranges (µg/mL) were 240-560 for HQ, 24-56 for MP, 132-308 for HCA, 6-14 for PP, 12-28 for BHT, 6.6-15 for TRT. During the validation process, the intra- and interday precision and trueness (evaluated as recovery) were found to be below 2.0% and between 100-102%, respectively. System suitability tests (SST) allow validating the herein proposed procedure specifically for pharmaceutical and industrial applications. SST test shows that the reported procedure fulfill with the Guidelines, allowing excellent separation of the analytes with very sensitive, accurate (precise and true) and reproducible quantitation of each analytes. The method was successfully applied in forced degradation studies of the six analytes. Specifically, acid degradation slightly affected HCA and BHT (91% recovery), while alkaline degradation drastically reduced HCA recovery (5.5%) and moderately affected BHT (85%). Photodegradation primarily influenced TRT quantity, and oxidative degradation intensified the BHT peak (130%).

Caffeine-folic acid-loaded-chitosan nanoparticles combined with methotrexate as a novel HepG2 immunotherapy targeting adenosine A2A receptor downstream cascade.

BACKGROUND: Methotrexate (MTX) is a common chemotherapeutic drug that inhibits DNA synthesis and induces apoptosis. Treatment with MTX increased CD73 expression, which leads to higher levels of extracellular adenosine. Adenosine levels are also high in the tumor microenvironment through Cancer cells metabolism. That promotes the survival of cancer cells and contributes to tumor immune evasion through the Adenosine 2a Receptor. A2A receptor antagonists are an emerging class of agents that treat cancers by enhancing immunotherapy, both as monotherapy and in combination with other therapeutic agents. Caffeine is an adenosine receptor antagonist. Herein, we demonstrate the ability of a novel well prepared and characterized nano formula CAF-FA-CS-NPs (D4) for A2aR blockade when combination with MTX to improve its antitumor efficacy by enhancing the immune system and eliminating immune suppression. METHODS: CAF-FA-CS-NPs (D4) were prepared and characterized for particle size, loading efficiency, and release profile. Molecular docking was used to validate the binding affinity of caffeine and folic acid to A2A receptor. The effects of the nano formula were evaluated on human liver cancer cells (HepG2), breast cancer cells (MCF-7), and MDA-MB-231, as well as normal human cells (WI-38). Different combination ratios of MTX and D4 were studied to identify the optimal combination for further genetic studies. RESULTS: Molecular docking results validated that caffeine and folic acid have binding affinity to A2A receptor. The CS-NPs were successfully prepared using ionic gelation method, with caffeine and folic acid being loaded and conjugated to the nanoparticles through electrostatic interactions. The CAF loading capacity in D4 was 77.9 ± 4.37% with an encapsulation efficiency of 98.5 ± 0.37. The particle size was optimized through ratio variations. The resulting nanoparticles were fully characterized. The results showed that (D4) had antioxidant activity and cytotoxicity against different cancer cells. The combination of D4 with MTX (IC50 D4 + 0.5 IC50 MTX) resulted in the downregulation of Bcl-2, FOXP3, CD39, and CD73 gene expression levels and upregulation of Bax and A2AR gene expression levels in HepG2 cells. CONCLUSIONS: This study suggests that CAF-FA-CS-NPs (D4) in combination with MTX may be a promising candidate for cancer immunotherapy, by inhibiting A2aR signaling and leading to improved immune activation and anti-tumor activity of MTX.

Analytical Methods for the Determination of Quercetin and Quercetin Glycosides in Pharmaceuticals and Biological Samples.

Flavonoids are plant-derived compounds that have several health benefits, including antioxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. Quercetin is a flavonoid that is widely present in various fruits, vegetables, and drinks. Accurate determination of quercetin in different samples is of great importance for its potential health benefits. This review, is an overview of sample preparation and determination methods for quercetin in diverse matrices. Previous research on sample preparation and determination methods for quercetin are summarized, highlighting the advantages and disadvantages of each method and providing insights into recent developments in quercetin sample treatment. Various analytical techniques are discussed including spectroscopic, chromatographic, electrophoretic, and electrochemical methods for the determination of quercetin and its derivatives in different samples. UV-Vis (Ultraviolet-visible) spectrophotometry is simple and inexpensive but lacks selectivity. Chromatographic techniques (HPLC, GC) offer selectivity and sensitivity, while electrophoretic and electrochemical methods provide high resolution and low detection limits, respectively. The aim of this review is to comprehensively explore the determination methods for quercetin and quercetin glycosides in diverse matrices, with emphasis on pharmaceutical and biological samples. The review also provides a theoretical basis for method development and application for the analysis of quercetin and quercetin glycosides in real samples.

The Potential Roles of Ficus carica Extract in the Management of COVID-19 Viral Infections: A Computer-Aided Drug Design Study.

INTRODUCTION: The conventional processes of drug discovery are too expensive, time-consuming and the success rate is limited. Searching for alternatives that have evident safety and potential efficacy could save money, time and improve the current therapeutic regimen outcomes. METHOD: Clinical phytotherapy implies the use of extracts of natural origin for prophylaxis, treatment, or management of human disorders. In this work, the potential role of common Fig (Ficus carica) in the management of COVID-19 infections has been explored. The antiviral effects of Cyanidin-3-rhamnoglucoside which is abundant in common Figs have been illustrated on COVID-19 targets. The immunomodulatory effect and the ability to ameliorate the cytokine storm associated with coronavirus infections have also been highlighted. This work involves various computational studies to investigate the potential roles of common figs in the management of COVID-19 viral infections. RESULTS: Two molecular docking studies of all active ingredients in common Figs were conducted starting with MOE to provide initial insights, followed by Autodock Vina for further confirmation of the results of the top five compounds with the best docking score. CONCLUSION: Finally, Molecular dynamic simulation alongside MMPBSA calculations were conducted using GROMACS to endorse and validate the entire work.

Smartphone-based point-of-care testing of the SARS-CoV-2: A systematic review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable diagnostic tests for comprehending and controlling the epidemic by tracking the world population. Given how crucial it is to monitor and manage the pandemic, researchers have recently concentrated on creating quick detection techniques. Although PCR is still the preferred clinical diagnostic test, there is a pressing need for substitutes that are sufficiently rapid and cost-effective to provide a diagnosis at the time of use. The creation of a quick and simple POC equipment is necessary for home testing. Our review's goal is to provide an overview of the many methods utilized to identify SARS-CoV 2 in various samples utilizing portable devices, as well as any potential applications for smartphones in epidemiological research and detection. The point of care (POC) employs a range of microfluidic biosensors based on smartphones, including molecular sensors, immunological biosensors, hybrid biosensors, and imaging biosensors. For example, a number of tools have been created for the diagnosis of COVID-19, based on various theories. Integrated portable devices can be created using loop-mediated isothermal amplification, which combines isothermal amplification methods with colorimetric detection. Electrochemical approaches have been regarded as a potential substitute for optical sensing techniques that utilize fluorescence for detection and as being more beneficial to the Minimizing and simplicity of the tools used for detection, together with techniques that can amplify DNA or RNA under constant temperature conditions, without the need for repeated heating and cooling cycles. Many research have used smartphones for virus detection and data visualization, making these techniques more user-friendly and broadly distributed throughout nations. Overall, our research provides a review of different novel, non-invasive, affordable, and efficient methods for identifying COVID-19 contagious infected people and halting the disease's transmission.

Lymphocyte to monocyte ratio predicts survival and is epigenetically linked to miR-222-3p and miR-26b-5p in diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. 10-20% of the patients present with bone marrow (BM) involvement which predicts a worse survival. This study aimed to determine the prognostic significance of serum miR-222-3p, miR-26b-5p, EBV-miR-BHRF1-2-5p, and EBV-miR-BHRF1-2-3p and correlate their levels to clinical and haematological markers in DLBCL with special emphasis on the lymphocyte-monocyte ratio (LMR) and neutrophil-monocyte ratio. We also studied the role of BM BMI1 and PIM2 proteins in predicting BM infiltration. Serum miRNAs were studied on 40 DLBCL and 18 normal individuals using qRT-PCR. BMI1 and PIM2 proteins were studied on BM biopsies by immunohistochemistry. The results were correlated with clinical and follow-up data. All the studied miRNAs were dysregulated in DLBCL serum samples. BMI1 and PIM2 were expressed in 67% and 77.5% of BM samples, respectively. LMR was significantly associated with disease-free survival (DFS) (P = 0.022), miR-222-3P (P = 0.043), and miR-26b-5p (P = 0.043). EBV-miR-BHRF1-2-3p was significantly correlated to haemoglobin level (P = 0.027). MiR-222-3p, miR-26b-5p, and EBV-miR-BHRF1-2-5p expressions were significantly correlated to each other (P = 0.001). There was no significant correlation between the studied markers and follow-up data. LMR is a simple method for predicting survival in DLBCL. MiR-222-3p and miR-26b-5p may be implicated in an immunological mechanism affecting patients' immunity and accordingly influence LMR. The correlation between miR-222-3p, miR-26b-5p, and EBV-miR-BHRF1-2-5p may indicate a common mechanism among the 3 miRNAs that may explain DLBCL pathogenesis.

Susceptibility phase imaging of deep gray matter: Presenting the effects of slice orientation.

Susceptibility-weighted image (SWI) is a T2* gradient echo sequence, which is highly sensitive to substances that have magnetic properties. The phase and magnitude of SWI can play an important role in the diagnosis of several diseases. The phase data is highly affected by spatial variations in the main magnetic field of the magnetic resonance imaging (MRI) scanner. The axial acquisition is the frequent plane alignment while acquiring SWI in diagnostic imaging. Clinical requirements often lead to changing of the alignment angles due to variability in patient positioning and anatomy. For many patients undergoing brain MRI, the line of the anterior and posterior commissure AC-PC can vary in direction with respect to the transverse plane of the MRI system. We investigated whether there exist significant effect on phase data of SWI, and this is due to oblique orientation. The obtained results showed significant differences in phase values between axial and anatomically alignments.

High Abdominal Perfusion Pressure Using Umbilical Cord Flap in the Management of Gastroschisis.

Background: Gastroschisis management remains a controversy. Most surgeons prefer reduction and fascial closure. Others advise staged reduction to avoid a sudden rise in intra-abdominal pressure (IAP). This study aims to evaluate the feasibility of using the umbilical cord as a flap (without skin on the top) for tension-free repair of gastroschisis. Methods: In a prospective study of neonates with gastroschisis repaired between January 2018 to October 2020 in Tanta University Hospital, we used the umbilical cord as a flap after the evacuation of all its blood vessels and suturing the edges of the cord with the skin edges of the defect. They were guided by monitoring abdominal perfusion pressure (APP), peak inspiratory pressure (PIP), central venous pressure (CVP), and urine output during 24 and 48 h postoperatively. The umbilical cord flap is used for tension-free closure of gastroschisis if PIP > 24 mmHg, IAP > 20 cmH2O (15 mmHg), APP <50 mmHg, and CVP > 15cmH2O. Results: In 20 cases that had gastroschisis with a median age of 24 h, we applied the umbilical cord flap in all cases and then purse string (Prolene Zero) with daily tightening till complete closure in seven cases, secondary suturing after 10 days in four cases, and leaving skin creeping until complete closure in nine cases. During the trials of closure, the range of APP was 49-52 mmHg. The range of IAP (IVP) was 15-20 cmH2O (11-15 mmHg), the range of PIP was 22-25 cmH2O, the range of CVP was 13-15 cmH2O, and the range of urine output was 1-1.5 ml/kg/h. Conclusion: The umbilical cord flap is an easy, feasible, and cheap method for tension-free closure of gastroschisis with limiting the PIP ≤ 24 mmHg, IAP ≤ 20 cmH2O (15 mmHg), APP > 50 mmHg, and CVP ≤ 15cmH2O.

Bile pulmonary embolism-related sudden death following an abdominal firearm injury: An autopsy case report and review of literature.

Bile pulmonary embolism (BPE) is a rare type of non-thrombotic pulmonary embolism (NTPE). For bile emboli to pass through the bloodstream to the lungs, there must be a connection created between the biliary and the venous vessels. This article reports a fatal BPE in a 12-year-old child who died 14 days following an abdominal firearm injury. The right lobe of the liver had a yellowish-green stained lacerated track along with bile collection. Both lungs were congested with peripheral dark areas in all lobes. Microscopically, many interstitial pulmonary arterioles were occluded by bile emboli along with the presence of hemorrhagic infarcts. Other than the present case, only 21 cases of BPE were published in the literature until the present day. The history of hepatic trauma and/or hepatobiliary disease in association with pulmonary manifestations points to BPE as a possible diagnosis. However, visualization of bile emboli within the pulmonary vessels is pathognomonic for BPE.

Direct acting anti-hepatitis C combinations as potential COVID-19 protease inhibitors.

The coronavirus pandemic could be the most threatening outbreak in the twenty-first century. According to the latest records of world health organization, more than 130 millions have been infected by COVID-19, with more than 2.9 million reported deaths. Yet, there is no magic cure for treatment of COVID-19. The concept of drug repurposing has been introduced as a fast, life-saving approach for drug discovery. Drug repurposing infers investigating already approved drugs for new indications, using the available information about pathophysiology of diseases and pharmacodynamics of drugs. In a recent work, more than 3000 FDA approved drugs were tested using virtual screening as potential antiviral agents for COVID-19. In this work, the top ranked five hits from the previous docking results together with drugs of similar chemical feature and/or mechanistic destinations were further tested using AutoDock Vina. The results showed that anti-HCV combinations could be potential therapeutic regimens for COVID-19 infections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00691-6.

Isolated Thoracoschisis: Case Report and Review of Literature.

A full-term male baby presented at day 2 postnatal with Riedel liver lobe, stomach, and much of the bowel herniating through a thoracic wall defect located just above and lateral to the left nipple. Operative conversion into a gastroschisis-like defect with construction of a silo bag was done. On thorough review of literature, it was found that this is only the second male infant reported with isolated thoracoschisis.

The detection of steroid sulfatase gene deletion (STS) in Egyptian males with X-linked ichthyosis.

BACKGROUND: Ichthyosis is a disorder of keratinization characterized by diffuse uniform and persistent scales resulting from abnormal epidermal differentiation or metabolism. The identification of steroid sulfatase (STS) as the cause of X-linked ichthyosis (XLI) points to the importance of this enzyme in skin desquamation. Fluorescent in situ hybridization (FISH) analysis is a good diagnostic technique with which to detect a common deletion of the STS gene. OBJECTIVE: In this study, the authors set out to detect the X-linked type of ichthyosis, diagnosed by detection of STS gene deletions among Egyptian males. METHODOLOGY: Egyptian males complaining of X-linked ichthyosis were clinically examined, evaluating pedigree analysis of the family, cytogenetic studies using G-banding technique and FISH using locus specific probe for steroid sulfatase (STS) gene which is located at chromosome Xp22.3. RESULTS: Of patients, 11.11 percent had nocturnal enuresis and 33.33 percent showed STS gene deletion by FISH analysis. CONCLUSION: This study underlines a difficulty in diagnosing X-linked ichthyosis on the clinical features or familial pedigree analysis in Egypt and the importance of cytogenetic and molecular cytogenetic studies for diagnosis. FISH analysis is a good, reliable and rapid diagnostic tool with which to detect STS gene deletion. Since FISH will not detect partial deletion or point mutations, the authors recommend further molecular studies to reach the proper diagnosis of X-linked ichthyosis.