Preparation, optimization, and characterization of genistein-ginseng long-acting polymeric gel as a breast cancer treatment alternative.

To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion's diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended.

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia.

Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.

Gut microbiota composition in patients with Crohn's disease in Saudi Arabia.

Crohn's disease (CD) entails intricate interactions with gut microbiome diversity, richness, and composition. The relationship between CD and gut microbiome is not clearly understood and has not been previously characterized in Saudi Arabia. We performed statistical analysis about various factors influencing CD activity and microbiota dysbiosis, including diagnosis, treatment, and its impact on their quality of life as well as high-throughput metagenomic V3-V4 16S rRNA encoding gene hypervariable region of a total of eighty patients with CD, both in its active and inactive state with healthy controls. The results were correlated with the demographic and lifestyle information, which the participants provided via a questionnaire. α-diversity measures indicated lower bacterial diversity and richness in the active and inactive CD groups compared to the control group. Greater dysbiosis was observed in the active CD patients compared to the inactive form of the disease, showed by a reduction in microbial diversity. Specific pathogenic bacteria such as Filifactor, Peptoniphilus, and Sellimonas were identified as characteristic of CD groups. In contrast, anti-inflammatory bacteria like Defluviitalea, Papillibacter, and Petroclostridium were associated with the control group. Among the various factors influencing disease activity and microbiota dysbiosis, smoking emerged as the most significant, with reduced α-diversity and richness for the smokers in all groups, and proinflammatory Fusobacteria was more present (p<0.05). Opposite to the control group, microbial diversity and richness were lower in CD participants of older age compared to younger ones, and male CD participants showed less diversity compared to women participants from the same groups. Our results describe the first report on the relationship between microbiota and Crohn's disease progress in Saudi Arabia, which may provide a theoretical basis for the application of therapeutic methods to regulate gut microbes in CD.

Municipal wastewater viral pollution in Saudi Arabia: effect of hot climate on COVID-19 disease spreading.

The viral RNA of SARS-Coronavirus-2 is known to be contaminating municipal wastewater. We aimed to assess if COVID-19 disease is spreading through wastewater. We studied the amount of viral RNA in raw sewage and the efficiency of the sewage treatment to remove the virus. Sewage water was collected before and after the activated sludge process three times during summer 2020 from three different sewage treatment plants. The sewage treatment was efficient in removing SARS-CoV-2 viral RNA. Each sewage treatment plant gathered wastewater from one hospital, of which COVID-19 admissions were used to describe the level of disease occurrence in the area. The presence of SARS-CoV-2 viral RNA-specific target genes (N1, N2, and E) was confirmed using RT-qPCR analysis. However, hospital admission did not correlate significantly with viral RNA. Moreover, viral RNA loads were relatively low, suggesting that sewage might preserve viral RNA in a hot climate only for a short time.

Trace elements-based Auroshell gold@hematite nanostructure: Green synthesis and their hyperthermia therapy.

Hyperthermia is an additional treatment method to radiation therapy/chemotherapy, which increases the survival rate of patients without side effects. Nowadays, Auroshell nanoparticles have attracted much attention due to their precise control over heat use for medical purposes. In this research, iron/gold Auroshell nanoparticles were synthesised using green nanotechnology approach. Auroshell gold@hematite nanoparticles were synthesised and characterised with rosemary extract in one step and the green synthesised nanoparticles were characterised by X-ray powder diffraction, SEM, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy analysis. Cytotoxicity of Auroshell iron@gold nanoparticles against normal HUVEC cells and glioblastoma cancer cells was evaluated by 2,5-diphenyl-2H-tetrazolium bromide method, water bath hyperthermia, and combined method of water bath hyperthermia and nano-therapy. Auroshell gold@hematite nanoparticles with minimal toxicity are safe against normal cells. The gold shell around the magnetic core of magnetite caused the environmental and cellular biocompatibility of these Auroshell nanoparticles. These magnetic nanoparticles with targeted control and transfer to the tumour tissue led to uniform heating of malignant tumours as the most efficient therapeutic agent.

Green Synthesis of Hexagonal Silver Nanoparticles Using a Novel Microalgae Coelastrella aeroterrestrica Strain BA_Chlo4 and Resulting Anticancer, Antibacterial, and Antioxidant Activities.

Microalgae-mediated synthesis of nanoparticles (NPs) is an emerging nanobiotechnology that utilizes the biomolecular corona of microalgae as reducing and capping agents for NP fabrication. This study screened a novel microalgal strain for its potential to synthesize silver (Ag)-NPs and then assayed the biological activities of the NPs. Coelastrella aeroterrestrica strain BA_Chlo4 was isolated, purified, and morphologically and molecularly identified. Chemical composition of the algal extract was determined by GC-MS analysis. Ag-NPs were biosynthesized by C. aeroterrestrica BA_Chlo4 (C@Ag-NPs) and characterized using various techniques. Antiproliferative activity and the biocidal effect of C@Ag-NPs, C. aeroterrestrica algal extract, and chemically synthesized Ag-NPs (Ch@Ag-NPs) were explored, and the scavenging activity of C@Ag-NPs against free radicals was investigated. C@Ag-NPs were hexagonal, with a nanosize diameter of 14.5 ± 0.5 nm and a maximum wavelength at 404.5 nm. FTIR and GC-MS analysis demonstrated that proteins and polysaccharide acted as capping and reducing agents for C@Ag-NPs. X-ray diffraction, energy diffraction X-ray, and mapping confirmed the crystallinity and natural structure of C@Ag-NPs. The hydrodynamic diameter and charge of C@Ag-NPs was 28.5 nm and -33 mV, respectively. C@Ag-NPs showed significant anticancer activity towards malignant cells, with low toxicity against non-cancerous cells. In addition, C@Ag-NPs exhibited greater antioxidant activity and inhibitory effects against Gram-positive and -negative bacteria compared with the other tested treatments. These findings demonstrate, for first time, the potential of a novel strain of C. aeroterrestrica to synthesize Ag-NPs and the potent antioxidant, anticancer, and biocidal activities of these NPs.

Pioglitazone Ameliorates Hippocampal Neurodegeneration, Disturbances in Glucose Metabolism and AKT/mTOR Signaling Pathways in Pentyelenetetrazole-Kindled Mice.

Disturbance of glucose metabolism, nerve growth factor (NGF) and m-TOR signaling have been associated with the pathophysiology of epilepsy. Pioglitazone (PGZ) is an anti-diabetic drug that shows a protective effect in neurodegenerative diseases including epilepsy; however, its exact mechanism is not fully elucidated. The present study aimed to investigate the potential neuroprotective effect of PGZ in pentylenetetrazole (PTZ) kindled seizure in mice. Swiss male albino mice were randomly distributed into four groups, each having six mice. Group 1 was considered the control. Epilepsy was induced by PTZ (35 mg/kg i.p.) thrice a week for a total of 15 injections in all other groups. Group 2 was considered the untreated PTZ group while Group 3 and Group 4 were treated by PGZ prior to PTZ injection at two dose levels (5 and 10 mg/kg p.o., respectively). Seizure activity was evaluated after each PTZ injection according to the Fischer and Kittner scoring system. At the end of the experiment, animals were sacrificed under deep anesthesia and the hippocampus was isolated for analysis of glucose transporters by RT-PCR, nerve growth factor (NGF) by ELISA and mTOR by western blotting, in addition to histopathological investigation. The PTZ-treated group showed a significant rise in seizure score, NGF and m-TOR hyperactivation, along with histological abnormalities compared to the control group. Treatment with PGZ demonstrated a significant decrease in NGF, seizure score, m-TOR, GLUT-1 and GLUT-3 in comparison to the PTZ group. In addition, improvement of histological features was observed in both PGZ treated groups. These findings suggest that PGZ provides its neuroprotective effect through modulating m-TOR signaling, glucose metabolism and NGF levels.

Possible vertical transmission of corona virus disease 19 (COVID-19) from infected pregnant mothers to neonates: a multicenter study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious with various possible routes of transmission, resulting in high mortality globally. Controversy exists regarding the vertical transmission of the SARS-CoV-2 infection to fetuses of COVID-19-infected women. The aim of this study was to investigate the possibility of the vertical transmission of SARS-CoV-2 from COVID-19-infected mothers to their neonates. MATERIALS AND METHODS: We prospectively collected demographical and clinical characteristics of 31 COVID-19 positive pregnant women and their neonates. All mothers and neonates were tested for SARS-CoV-2 infection using the real-time polymerase chain reaction on nasopharyngeal swabs and breast milk samples. Antenatal and placental abnormalities were ultrasonically and histopathologically examined. In cord blood samples, the immunoglobins (Ig) M and IgG were estimated qualitatively. RESULTS: The women's mean age and gestational age were 31 years and 38 weeks, respectively, with 58% undergoing an elective cesarean section. Gestational diabetes was reported in 29% of cases, 64.5% of women were medically free and only 16.12% were symptomatic. A normal antenatal ultrasound was observed in 77.42% of cases. Nine cord blood samples were positive for IgG. Villous infarction (24%), villous agglutination, and chorangiosis (51%), accelerated villous maturation (21%) and reduced and hypercoiling were reported for 6.97% of the umbilical cords. Three newborns had possible vertical transmission of SARS-CoV-2 infection, of which, two were preterm and IUFD. The third neonate was born full-term, admitted to NICU and later discharged in good health. CONCLUSION: Our findings support the possibility of the direct vertical transmission of the SARS-CoV-2 infection to neonates from infected mothers. Further studies with a larger sample size are required to validate the current findings.

Clinical profiles associated with SARS-CoV-2 infection and complications from coronavirus disease-2019 in children from a national registry in Saudi Arabia.

CONTEXT: Exploring clinical characteristics of coronavirus disease-19 (COVID-19) in children may help in prevention and treatment guidelines. AIMS: The aim of the to describe the spectrum of pediatric COVID-19 in Saudi Arabia. SETTINGS AND DESIGN: A multicenter, retrospective, cross-sectional study involving pediatric COVID-19 patients across all Saudi regions. METHODS: All patients aged between 2 months and 18 years with a confirmed diagnosis of COVID-19 were included. The primary end point was the hospitalization. STATISTICAL ANALYSIS USED: Descriptive statistics were used to describe the baseline demographic data and clinical characteristics. Numerical data were explored using Kolmogorov-Smirnov test and Shapiro-Wilk test, while Chi-square or Fisher's exact test were used for categorical data. RESULTS: Among the 654 pediatric COVID-19 patients, 4.7% (n = 31) were hospitalized, with one patient only needing pediatric intensive care admission. Sex, breastfeeding, birth status, and the patients' living environment showed no significant association with hospitalization. Most children (80.3%, n = 525) were symptomatic, with two symptoms that were significantly associated with admission, namely, vomiting (P = 0.007) and nausea (P = 0.026). History of admission within the last year was identified in 10.4% (n = 68) children but had no association with worse outcome. The median duration of hospitalization for the entire group was 5.5 days, with longest hospital stay for age group 7-12 years (median 6 days). CONCLUSIONS: COVID-19 is usually a milder disease in children. Although having preexisting medical conditions was linked to a longer hospitalization, it was not associated with worse outcome. Continuous surveillance will allow additional characterization of the burden and outcomes of pediatric COVID-19-associated hospitalizations.

A review on Saudi Arabian wastewater treatment facilities and available disinfection methods: Implications to SARS-CoV-2 control.

COVID-19 pandemic has severe impacts on human health and economy worldwide. Aerosols and droplets are the major routes of transmission of SARS-CoV-2 coronavirus causing COVID-19 disease. However, wastewater is a possible transmission pathway. Therefore, many studies have been published about the relation of wastewater and COVID-19 disease. Many studies have shown the presence of viral RNA in wastewater throughout the world recently. Therefore, research on wastewater treatments and disinfection methods are needed. Communities must make sure that the virus is not transmitted via treated wastewater. This review focuses on the Saudi Arabian wastewater treatment and disinfection techniques to assess the possibility of SARS-CoV-2 transmission through wastewaters. In view of the current pandemic situation, the wide analysis of wastewater treatments in Saudi Arabia is needed. The review gives guidelines to develop the wastewater treatment in Saudi Arabia.

COVID-19 Pandemic Causing Depression in Different Sociodemographic Groups in Saudi Arabia.

COVID-19 disease was announced as a global pandemic in March 2020 by the World health organization (WHO). Saudi Arabia was among the first countries to enforce restriction measures such as closing schools, remote working, and a travel ban. We aim to evaluate the impact of the COVID-19 pandemic on people's depression in Saudi Arabia. A cross-sectional online survey of 1109 participants was conducted during the curfew between 18th of May and 11th of June 2020. An online questionnaire included questions about the commitment to follow the precautionary measures, knowledge on COVID-19, and depression. Depression was assessed with the Impact of Event Scale-Revised method. Females, unmarried individuals, elderly persons, parents of young children, unemployed, and small families were more likely to be depressed. Education level did not explain the differences in depression. However, the more knowledge the participants had about COVID-19 the better they followed the restrictions. A regression analysis revealed that the commitment of a person to follow the restrictions increased his/her depression symptoms. Attention should be paid to different groups of people in future psychiatric planning.

An analytical study on the awareness, attitude and practice during the COVID-19 pandemic in Riyadh, Saudi Arabia.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by a new variable of the Coronaviridae family. COVID-19 spreads primarily by contacting the virus either from a COVID-19-infected individual through coughing or sneezing or from COVID-19-contaminated surfaces. On March 12, 2020, the World Health Organization (WHO) announced COVID-19 as a pandemic. The government of Saudi Arabia was among the first countries in the world to take quick and serious precautions. The Ministry of Health (MOH) has made the public aware of the virus transmission patterns and the importance of quarantine and curfew. Despite strict measures taken, the awareness of people towards infectious viruses remains the most important factor in limiting the widespread of diseases. METHOD: A cross-sectional survey of 1767 participants, was conducted to explore the awareness, attitude and practice of COVID-19 in relation to socioeconomic data among residents in the city of Riyadh. RESULTS: Of all the participants, 58% showed a moderate level of awareness, 95% presented a high attitude and 81% presented an adequate practice regarding COVID-19. Significant positive correlation between awareness-attitude (r = 0.132, p-value < 0.001) and attitude-practice (r = 0.149, p-value < 0.001) were found. The gender of the participants was the only common characteristic significantly associated with both awareness and practice. This study revealed that males showed a slight increase (60%) in the level of awareness compared to female participants (57%), however, when it comes to the practice towards COVID-19, females showed slightly better practice (82%) than males (80%). The World health organization (WHO) and the Ministry of Health (MOH) were the main sources of information. CONCLUSION: Despite the moderate public awareness, their attitude and practice were better. Therefore, public awareness must be improved to be prepared for epidemic and pandemic situations. A comprehensive public health education program is important to increase awareness and to reach sufficient knowledge.

Controlling COVID-19 Pandemic: A Mass Screening Experience in Saudi Arabia.

A highly accelerating number of people around the world have been infected with novel Coronavirus disease 2019 (COVID-19). Mass screening programs were suggested by the World Health Organization (WHO) as an effective precautionary measure to contain the spread of the virus. On 16 April 2020, a COVID-19 mass screening program was initiated in Saudi Arabia in multiple phases. This study aims to analyze the number of detected COVID-19 cases, their demographic data, and regions most affected in the initial two phases of these mass screening programs. A retrospective cross-sectional study was conducted among the high-risk population as part of the COVID-19 mass screening program across all regions in Saudi Arabia during April and May 2020. A Chi-square-test was used to determine the associations between positive cases and various demographic variables. Out of 71,854 screened individuals, 13.50% (n = 9701) were COVID-19 positive, of which 83.27% (n = 59,835) were males. Among positive cases, in the 30-39 years age group, 6.36% were in the active phase, and 2.19% were in the community phase. Based on our experience, launching mass screening programs is crucial for early case detection, isolation, and pattern recognition for immediate public interventions.