The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model.

Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.

Neck Pain Disability and Smartphone Addiction Among College Students Before and During COVID-19 Confinement: A Pilot Study.

The COVID-19 pandemic has resulted in an increase in the use of smartphone technology, which can be associated with several negative health effects such as neck pain disability. The present study explored the association between smartphone addiction and disability associated with neck pain among female health science students before and 2 months after the start of COVID-19 confinement. Data were obtained for this pilot study from 39 students before the pandemic and 2 months after the start of confinement using two self-administered questionnaires, the Neck Disability Index and Smartphone Addiction Scale Short Version. The results showed that while there was an increase in smartphone use after the start of confinement, the before and after confinement difference was negligible. Surprisingly, smartphone addiction and neck pain disability seemed to decrease after the start of the confinement. Further, while there was a moderate but significant correlation between smartphone addiction and neck pain disability before the COVID-19 confinement, this correlation was insignificant after the start of confinement. These findings could be explained by other factors, such as the position in which the devices were used, but they need to be investigated further through larger multicenter cohorts with long-term follow-up.

Chitosan-based films blended with moringa leaves and MgO nanoparticles for application in active food packaging.

This study aims to address the issue of environmental pollution caused by non-biodegradable petroleum-based food packaging by exploring the application of biodegradable films. Film casting was employed to fabricate food packaging films from chitosan (CS) and polyvinyl alcohol (PVA) polymers blended with moringa extract (MoE) and various concentrations of magnesium oxide nanoparticles (MgO NPs). The films were characterized through multiple techniques, including UV spectroscopy, Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDX), X-ray Diffraction (XRD), and Fourier-transform Infrared Spectroscopy (FTIR). The study investigated the physicomechanical properties, water solubility, water vapor transmission rate, oxygen permeability, migration test, biodegradability, contact angle, anti-fogging, antibacterial and antifungal activity, and application of the films for food packaging. The results showed that blending CS/PVA films with MoE and MgO NPs significantly improved their mechanical properties. The highest tensile strength of 98 MPa was observed in the CPMMgO-0.5 film. The solubility of the films was low, with CPMMgO-0 and CPMMgO-0.25 demonstrating the lowest solubility as weight decreased by 3.41 % and 3.47 %, respectively. The water vapor transmission rate and oxygen permeability decreased with increasing MgO NP concentrations, with the CPMMgO-0.5 film exhibiting the lowest values. The films also demonstrated good biodegradability, anti-fogging ability, antibacterial and antifungal activity, and low water solubility, enabling bead encapsulation over 14 days in good condition. Moreover, the thermal stability of the films was improved, extending the shelf life of bread. Therefore, the fabricated films provide a promising alternative to non-degradable plastic packaging, which heavily contributes to environmental pollution.

Comparative Real Life Egyptian Experience of the Combination of Sofosbuvir Plus Daclatasvir or Simeprevir for 12 Weeks in Naïve Cirrhotic Patients Infected with HCV Genotype 4.

BACKGROUND: Chronic infection with HCV is progressive worldwide health problem and the core reason for liver cirrhosis, portal hypertension, or hepatocellular carcinoma. HCV-G4 represents the most common threat to transplantation of the liver in Egypt. New interferon-free regimens have been started consuming direct-acting antiviral oral tablets for HCV cure. OBJECTIVES: In the current study, comparing the safety and efficacy of DAAs combination regimens including sofosbuvir with daclatasvir or sofosbuvir with simeprevir plus ribavirin for naïve cirrhotic Egyptian patients infected with HCV-G4 was our main goal. METHODS: We recruited 150 naïve cirrhotic HCV patients from the Tropical patients' clinic at Fayoum General Hospital. They were classified randomly into two groups, group one (n=75 patients) were administrated Sofosbuvir plus simeprevir (400 mg and 150 mg once daily respectively ) for twelve weeks, and group two (n=75 patients) were administrated Sofosbuvir plus Daclatasvir (400 mg and 60 mg once daily respectively) with ribavirin (1-1.2 gm daily weight-based) for twelve weeks. Clinical follow-up, laboratory investigations, and viral PCR were measured to detect treatment efficacy, safety, and any adverse events. RESULTS: Sustained virological response rates (SVR12) were 92%and 90.7% in the first and second groups, respectively. The major unfavorable events were fatigue, arthralgia, and weight loss without statistically meaningful differences between study groups. However, anemia and headache were significantly widespread in the second group (P=0.0161 and 0.0495, respectively). We observed four patients with photosensitivity in group I and not observed in the second group. CONCLUSION: The current study revealed that DAAs are safe and effective in the cure of naïve cirrhotic patients chronically infected by HCV-G4 with better results in those treated with sofosbuvir plus simeprevir regimen.

Novel zinc-silver nanocages for drug delivery and wound healing: Preparation, characterization and antimicrobial activities.

Metal organic framework (MOF)-nanocages (MOF-NCs) in the form of zinc-based nanoparticles (NPs) were synthesized as drug carriers for the purpose of wound healing. The prepared NCs (single and bi-metallic with silver-MOF) were based on zinc and they were loaded with ascorbic acid (vitamin C) as a model drug which accelerates wound healing. The NCs were then investigated by several characterization techniques such as XRD, TEM, FTIR and BET surface area. Furthermore, the release behavior of the loaded ascorbic acid from the developed NCs was measured in phosphate buffer solution (PBS). NCs antibacterial activity was tested against strain of gram-positive bacteria (Staphylococcus aureus ATCC- 29213, Streptococcus pyogenes ATCC-19615 and Bacillus subtilis ATCC-6633), gram-negative bacteria strain (Pseudomonas aeruginosaATCC-27853and Escherichia coli ATCC-25922) and fungi (Candida albicans ATCC-10231).The physicochemical features of the NCs were confirmed by the results obtained from XRD and FTIR measurements. The particle size of the NCs was confirmed to be in the range of 30-50 nm. Prolonged drug release that was combined with impressive antibacterial activities, and good wound healing rates were also recognized for the zinc based NCs in comparison to commonly used Ag NPs. It is concluded that the current NCs are potentially suitable for wound healing and drug delivery applications.

Middle-East OBGYN graduate education (MOGGE) foundation practice guidelines: use of labor charts in management of labor. Practice guideline no. 04-O-21.

Since the 50 s of the last century, labor charts have been proposed and appraised as a tool to diagnose labor abnormalities and guide decision-making. The partogram, the most widely adopted form of labor charts, has been endorsed by the world health organization (WHO) since 1994. Nevertheless, recent studies and systematic reviews did not support clinical significance of application of the WHO partogram. These results have led to further studies that investigate modifications to the structure of the partogram, or more recently, to reconstruct new labor charts to improve their clinical efficacy. This guideline appraises current evidence on use of labor charts in management of labor specially in low-resource settings.

Efficacy and Safety of Ombitasvir plus Paritaprevir, Ritonavir and Ribavirin in Non-cirrhotic Treatment-naïve and Treatment-experienced Egyptians with Chronic HCV Genotype-4 Infection.

Hepatitis C virus genotype 4 (HCV-GT4) is a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. A combination of three new direct-acting antivirals ombitasvir, paritaprevir, and ritonavir has been recommended for treatment of HCV-GT4 infection. The current study was aimed to assess the efficacy and safety of this combination plus ribavirin in non-cirrhotic, treatment-naïve and -experienced Egyptians with HCV-GT4 infection in a real-world setting. A total of 255 Egyptians with HCV-GT4 infection were enrolled, including 82 treatment-experienced and 173 treatment-naïve patients. All of them completed 12-week treatment protocol of ombitasvir, paritaprevir and ritonavir as an oral dose combination with ribavirin. Virological response (VR) was measured, as well as the biochemical parameters related to treatment efficacy and adverse events at baseline and after treatment, at 4 (VR4) and 12 (VR12) weeks post-treatment. The results showed that the VR4 rates were 98.8% in both groups, and VR12 rates were 97.7% and 96.3% in treatment-naïve and -experienced patients, respectively, with no significant differences found between the groups concerning VR4 (P=0.9) and VR12 (P=0.3). The most common adverse events were headache and fatigue, which were significantly more common (P=0.001 and 0.003, respectively) in treatment-experienced than in treatment-naïve group. The quadruple regimen was well-tolerated, and the reported adverse events were generally mild to moderate. This real-world setting study confirms that the combination of ombitasvir, paritaprevir, ritonavir, and ribavirin is highly effective in the treatment of HCV- GT4 infection with a good safety and tolerability profile.

The combined antibacterial and anticancer properties of nano Ce-containing Mg-phosphate ceramic.

AIM: This paper was mainly aimed at synthesis of Ce-containing nano-Mg-phosphate ceramic as a multifunctional material. MATERIALS AND METHODS: Two ceramics based on Mg3(PO4)2 and Ce0.2Mg2.8(PO4)2 formulas (MP and MP-C, respectively) were synthesized. The synthesized powders were characterized by XRD, TEM, Zeta potential, and FTIR. Also, their dissolution behavior was tested in Tris-HCl buffer solution. Moreover, the antimicrobial efficacy was evaluated against gram-positive bacteria (Bacillus sphaericus MTCC 511 &Staphylococcus aureus MTCC 87) and gram-negative bacteria (Enterobacter aerogenes MTCC 111 &Pseudomonas aeruginosa MTCC 1034) using dick diffusion assay and microdilution method. Furthermore, the cell viability test was performed for the ceramics on Vero cells (African green monkey kidney cells), and their antitumor activity was determined by PC3 cell line (prostatic cancer). Also, the cellular uptake was determined by the flow cytometry. KEY FINDINGS: The results showed that the substitution of Mg by Ce decreased the particle size from 40 to 90 nm for MP sample to 2-10 nm for MP-C sample and increased the degradation rate. Both samples showed excellent antimicrobial activities. Moreover, MP demonstrated more cell viability than MP-C on Vero cells at high concentrations, whereas, MP-C showed more antitumor activity on PC3 cells than MP sample. Moreover, MP-C showed a higher cell uptake than MP due to its smaller size and more negative charge. SIGNIFICANCE: Mg-phosphate ceramic can be used in this study successfully as a delivery system for cerium ions and showed a high antitumor activity, which makes it highly recommended as safe and effective cancer treatment materials.

Evaluation of the diagnostic and therapeutic roles of non-coding RNA and cell proliferation related gene association in hepatocellular carcinoma.

Micro RNA-34a-5p (miR-34a-5p) is an important molecule that can act as a modulator of tumor growth. It controls expression of a plenty of proteins controlling cell cycle, differentiation and apoptosis and opposing processes that favor viability of cancer cells, their metastasis and resistance to chemotherapy. Bioinformatics analysis indicated that minichromosome maintenance protein 2 (MCM2) is a target gene of miR-34a-p. In this study, RT-qPCR was employed to detect the expression of miR-34a-5p and MCM2 in 10 hepatocellular carcinoma (HCC) tissues. The functional role of miR-34a-5p in HCC was investigated and the interaction between miR-34a-5p and MCM2 was explored. Results showed miR-34a-5p expression in HCC tissues was significantly lower than in non HCC liver tissues (P < 0.05), but MCM2 expression in HCC tissues was markedly higher than in non HCC liver tissues (P < 0.05). In addition, miR-34a-5p expression was negatively related to MCM2 expression. To confirm effect of miR-34a-5p on tumor growth and its possible effect on MCM2, miR-34a-5p mimic and inhibitor was transfected into HCC cell lines (HepG2). MTS assay, showed miR-34a-5p over-expression could inhibit the proliferation of HCC cells. RT-qPCR was done to detect the expression of miR-34a-5p and MCM2 in HepG2 cells before and after transfection. Results showed that MCM2 expression in HCC tissues was markedly lower in mimic transfected group than in inhibitor transfected group and control group (P < 0.05) while miR-34a-5p expression in HepG2 cells was significantly higher in mimic transfected group than in inhibitor transfected group and control group (P < 0.05). Thus, miR-34a-5p may inhibit the proliferation of HCC cells via regulating MCM2 expression. These findings provide an evidence for the emerging role of microRNAs as diagnostic markers and therapeutic targets in HCC.

In vitro drug release behavior of Ce-doped nano-bioactive glass carriers under oxidative stress.

Ce-containing bioactive glasses are known to decrease reactive oxygen activities inside the body. That is because of their excellent catalytic activities which come from the fast interchange of Ce3+/Ce4+ oxidation states. This research was mainly aimed at preparing new Ce-doped nano-bioactive glasses based on 60SiO2-(10-x)B2O3-25CaO-5P2O5-xCeO2, in mole% (x = 0 and 5 mol%) as multifunctional bone fillings. Moreover, the glasses were used as a delivery system for ciprofloxacin to intensely solve the bone infection complications. Nevertheless, there were no previous works studied of the nature immersing solution effect on the drug release behavior from Ce-doped nano-bioactive glass carriers. Therefore, phosphate-free and phosphate-containing buffer solutions with/without superoxide species (H2O2) were used to investigate the efficacy of this drug delivery system in different environment. The results showed that Ce addition enhanced the formation of apatite layer and cell viability. Moreover, the percentage of released drug was apparently affected by the glass composition and nature of soaking fluid, specifically, in the media containing superoxide species (H2O2). In conclusion, the prepared Ce-doped glass nanoparticles illustrated multifunctional bone filling material, but when it intended to be utilized as a drug delivery system, the nature of surrounding medium have to be taken into consideration.

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4+CD28null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4+CD28null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4+CD28null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4+CD28null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4+CD28null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4+CD28null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4+CD28null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

The transmembrane domain of the Staphylococcus aureus ESAT-6 component EssB mediates interaction with the integral membrane protein EsaA, facilitating partially regulated secretion in a heterologous host.

The ESAT-6-like secretion system (ESS) of Staphylococcus aureus plays a significant role in persistent infections. EssB is a highly conserved bitopic ESS protein comprising a cytosolic N-terminus, single transmembrane helix and a C-terminus located on the trans-side of the membrane. Six systematic truncations covering various domains of EssB were constructed, followed by bacterial two-hybrid screening of their interaction with EsaA, another conserved integral membrane component of the ESS pathway. Results show that the transmembrane domain of EssB is critical for heterodimerization with EsaA. In vivo crosslinking followed by Western blot analysis revealed high molecular weight species when wild-type EssB and EsaA were crosslinked, but this band was not detected in the absence of the transmembrane domain of EssB. Heterologous overproduction of EssB, EsaA and five other components of the ESS pathway in Escherichia coli BL21(DE3), followed by fractionation experiments led to a remarkable increase in the periplasmic protein content, suggesting the assembly of partially regulated secretion mechanism. These data identify the transmembrane domain of EssB as indispensable for interaction with EsaA, thereby facilitating protein secretion across bacterial membranes in a fashion that requires other components of the ESS pathway.