Chitosan-dipotassium orthophosphate lyophilizate: a novel in situ thermogel carrier system of allogeneic platelet lysate growth factors

The clinical success of platelet-rich plasma (PRP) is constrained by its limited mechanical strength, rapid disintegration by lytic enzymes, and the consequent short-term release of bioactive growth factors (GFs). Recently, attempts to formulate PRP and other hemoderivatives, such as platelet lysate (PL) have been underway. The current study aimed to formulate allogeneic freeze-dried human platelet lysate (HPL) onto lyophilized chitosan - dipotassium hydrogen orthophosphate (CS/DHO) thermo-sensitive scaffolds. A systemic approach was employed to optimize freeze-drying (FD) procedures targeting predefined critical quality attributes (CQAs). Thermal behavior, vibrational spectroscopy, morphological and moisture content analyses were used to detect possible protein destabilization during formulation and suboptimal cake properties. The effect of CS/DHO concentrations on thermo-responsiveness and release kinetics were investigated. Finally, six-months stability and cytotoxicity studies were carried out. An optimized lyophilizate was attainable with residual moisture of less than 5% and thermoresponsive to 33 °C in less than 3 min. HPL proteins were sustainedly released over five days in a pH-sensitive manner. The stability study indicated plausible physical and biochemical stability. Cell viability testing supported the cytocompatibility of the system. Finally, the lyophilizate variant of CS/DHO thermogel overcomes limited storage stability previously posed as a challenge in freshly prepared thermogels. The developed system overcomes the drawbacks of currently used PRP treatment and provides a novel GF-rich scaffold for wound repair.     

The efficacy and safety of extended adjuvant temozolomide following concurrent radio-chemotherapy among Egyptian patients with newly diagnosed glioblastoma multiforme

Although concurrent radio-chemotherapy and adjuvant temozolomide (TMZ) treatment for 6 cycles has been established as a standard of care for newly diagnosed glioblastoma multiforme (GBM) patients, the recommended duration of adjuvant TMZ remains a matter of debate. Hereby, we aimed to report for the first time our experience from Upper Egypt through comparing survival and toxicity profile between two treatment modalities of adjuvant TMZ (> six cycles versus six cycles) and delineating factors of prognostic significance in Egyptian patients with newly diagnosed GBM treated by radiation therapy with concomitant and adjuvant TMZ. Between June 2016 and February 2018, the medical records of 121 patients were eligible to be retrospectively reviewed to extract the study relevant data. All patients received concurrent radio-chemotherapy, followed by TMZ for 6 cycles in 29 patients (Group 1) and for >6 cycles in 26 patients (Group 2). Patients in Group 1 had a median PFS of 15 months (95% CI: 10.215-19.785), while those in Group 2 had a median PFS of 18 months (95% CI: 16.611-19.389). After a median follow up duration of 20 months (range: 12-41), the median OS was 18 months (95% CI: 13.420-22.580) in Group 1 and 22 months (95% CI: 18.777-25.223) in Group 2. There was no statistically significant correlation between the number of chemotherapy cycles and PFS (P=0.513) or OS (P=0.867). The extent of surgical resection was the only independent prognostic factor for both PFS (P=0.015) and OS (P=0.028) by multivariate analysis. Three grade ≥3 hematologic toxicity were encountered in 3 patients. One in the six-cycle group (neutropenia), and two in the extended cycles group (one had neutropenia and the other one developed thrombocytopenia). No statistically significant difference in the toxicity profile between both groups. The results of our study suggest that extended TMZ therapy is safe and tolerable, however it did not significantly improve PFS or OS as compared to the standard six-cycle course. Larger randomized studies are required to shed more light on this issue.     

Metabolome-based profiling of African baobab fruit (Adansonia digitata L.) using a multiplex approach of MS and NMR techniques in relation to its biological activity

Adansonia digitata L. also known as African baobab is one of the most important fruit-producing trees, widely distributed in the African continent. Baobab fruits are known to possess potential health benefits and nutritional value. This study aimed to holistically dissect the metabolome of A. digitata fruits using a novel comparative protocol using three different analytical platforms. Ultra high performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-HRMS/MS), and headspace solid-phase microextraction/gas chromatography coupled to mass spectrometry (HS-SPME/GC-MS) were respectively employed for phytonutrients and aroma profiling, whereas GC-MS post silylation provided an overview of nutrients i.e., sugars. UHPLC-HRMS/MS analysis allowed for the assignment of 77 metabolites, among which 50% are reported for the first time in the fruit. While GC-MS of silylated and aroma compounds led to the identification of 74 and 16 compounds, respectively. Finally, NMR-based metabolite fingerprinting permitted the quantification of the major metabolites for future standardization. In parallel, in vivo antidiabetic potential of the baobab fruit using a streptozotocin (STZ) induced diabetic rat model was assessed. Histopathological and immune-histochemical investigations revealed hepatoprotective and renoprotective effects of A. digitata fruit along with mitigation against diabetes complications. Moreover, the administration of A. digitata fruits (150 mg kg⁻¹) twice a week lowered fasting blood glucose levels.

Metabolites profiling of Adansonia digitata L. in relation to its biological activity.     

Study of the gut Microbiome Profile in Children with Autism Spectrum Disorder: a Single Tertiary Hospital Experience

The role of gut microbiome was recently raised in the pathogenesis of neurodevelopmental disorders including autism spectrum disorder (ASD). The aim of this study was to elucidate changes in gut microbiome in Egyptian autistic children and its possible correlation with the severity of autism and gastrointestinal (GI) symptoms. The gut bacterial microbiome of 41 ASD children, 45 siblings, and 45 healthy controls were analyzed using quantitative SYBR Green real-time PCR technique targeting 16S rRNA of selected bacteria. The gut microbiome of ASD children and their siblings contained a higher relative abundance of Bacteroides as well as Ruminococcus than controls. Prevotella/Bacteroides (P/B) ratio and Firmicutes/Bacteroidetes (F/B) were significantly lower in both ASD cases and their siblings. The only difference between the autistic cases and their siblings was the significantly higher level of Bifidobacterium in siblings, which appears to offer them a protective role. There was no correlation between the altered gut microbiome and the severity of autism or GI symptoms. The current study showed an evidence of changes in the gut microbiome of autistic children compared to the unrelated control. However, the microbiome profile of siblings was more like that of autistic children than that of unrelated controls indicating that gut microbiota is affected by dietary habits, living conditions together with host genetic factors.     

Physical activity and mental well-being during COVID-19 pandemic

The corona virus disease 2019 (COVID-19) pandemic has resulted in most nations deciding upon self-isolation and social distancing policies for their citizens to control the pandemic and reduce hospital admission. This review aimed at evaluating the effect of physical activity on mental well-being during the COVID-19 pandemic. It was concluded that the COVID-19 pandemic may lead to augmented levels of angiotensin-converting enzyme (ACE)-2 that led to cardiovascular and neurological disorders associated with highly inflammatory effects of viral infection affecting the brain tissues leading to damage of the nervous system and resulting in cognition dysfunction, insulin sensitivity reduction, and behavioral impairments. Anxiety and depression may lead to negative effects on various quality of life domains, such as being physically inactive. Regular physical activities may reduce inflammatory responses, improve ACE-2 responses, and improve mental well-being during self-isolation and social distancing policies related to the COVID-19 pandemic. Further studies should be conducted to assess the different intensities of physical activities on cardiovascular function, and mental well-being during the COVID-19 pandemic.     

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.     

Magnesium ascorbyl phosphate vesicular carriers for topical delivery; preparation,in-vitro and ex-vivo evaluation,factorial optimization and clinical assessment in melasma patients

Ascorbic acid (vitamin C) is an antioxidant that is widely used in cosmetics in skincare products. Due to the excessive low stability of ascorbic acid in cosmetic formulations, the stabilized ascorbic acid derivative, magnesium ascorbyl phosphate (MAP) was formulated as vesicular carriers; ethosomes and niosomes. The aim was to deliver MAP at the intended site of action, the skin, for sufficient time with enhanced permeation to get an effective response. Ethosomes were formulated using a full 3² factorial design to study ethanol and phospholipid concentration effect on ethosomes properties. Niosomes were formulated using 2³ factorial designs to study the effect of surfactant type, surfactant concentration and cholesterol concentration on niosomes properties. The prepared formulations were evaluated for their Entrapment efficiency, particle size, polydispersity index, zeta potential and % drug permeated. The optimized ethosomal and niosomal formulations were incorporated into carbopol gel and evaluated for their permeation, skin retention and stability. A comparative split-face clinical study was done between the ethosomal and niosomal formulations for melasma treatment using Antera 3 D^® camera. The optimized ethosomal and niosomal gels showed comparable controlled permeation and higher skin retention over their ethosomes and niosomes formulations respectively. Magnesium ascorbyl phosphate ethosomal gel showed clinically and statistically significant melanin level decrease after one month while MAP niosomal gel showed clinically and statistically significant melanin level decrease after six months. A combination of MAP ethosomes and niosomes could be promising skincare formulations for melasma and hyperpigmentation short and long-term treatment.     

Spent Coffee Grounds Valorization as Bioactive Phenolic Source Acquired Antifungal,Anti-Mycotoxigenic,and Anti-Cytotoxic Activities

Spent coffee grounds (SCGs), which constitute 75% of original coffee beans, represent an integral part of sustainability. Contamination by toxigenic fungi and their mycotoxins is a hazard that threatens food production. This investigation aimed to examine SCGs extract as antimycotic and anti-ochratoxigenic material. The SCGs were extracted in an eco-friendly way using isopropanol. Bioactive molecules of the extract were determined using the UPLC apparatus. The cytotoxicity on liver cancer cells (Hep-G2) showed moderate activity with selectivity compared with human healthy oral epithelial (OEC) cell lines but still lower than the positive control (Cisplatin). The antibacterial properties were examined against pathogenic strains, and the antifungal was examined against toxigenic fungi using two diffusion assays. Extract potency was investigated by two simulated models, a liquid medium and a food model. The results of the extract showed 15 phenolic acids and 8 flavonoids. Rosmarinic and syringic acids were the most abundant phenolic acids, while apigenin-7-glucoside, naringin, epicatechin, and catechin were the predominant flavonoids in the SCGs extract. The results reflected the degradation efficiency of the extract against the growth of Aspergillus strains. The SCGs recorded detoxification in liquid media for aflatoxins (AFs) and ochratoxin A (OCA). The incubation time of the extract within dough spiked with OCA was affected up to 2 h, where cooking was not affected. Therefore, SCGs in food products could be applied to reduce the mycotoxin contamination of raw materials to the acceptable regulated limits.