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An insight into the role of experimental parameters in advanced oxidation process applied for pharmaceutical degradation

Qutob M, Alshehri S, Shakeel F, Alam P, Rafatullah M

Environ Sci Pollut Res Int, 2024 Apr;31(18):26452-26479.
PMID: 38546921 DOI: 10.1007/s11356-024-33040-3

The advanced oxidation process (AOP) is an efficient method to treat recalcitrance pollutants such as pharmaceutical compounds. The essential physicochemical factors in AOP experiments significantly influence the efficiency, speed, cost, and safety of byproducts of the treatment process. In this review, we collected recent articles that investigated the elimination of pharmaceutical compounds by various AOP systems in a water medium, and then we provide an overview of AOP systems, the formation mechanisms of active radicals or reactive oxygen species (ROS), and their detection methods. Then, we discussed the role of the main physicochemical parameters (pH, chemical interference, temperature, catalyst, pollutant concentration, and oxidant concentration) in a critical way. We gained insight into the most frequent scenarios for the proper and improper physicochemical parameters for the degradation of pharmaceutical compounds. Also, we mentioned the main factors that restrict the application of AOP systems in a commercial way. We demonstrated that a proper adjustment of AOP experimental parameters resulted in promoting the treatment performance, decreasing the treatment cost and the treatment operation time, increasing the safeness of the system products, and improving the reaction stoichiometric efficiency. The outcomes of this review will be beneficial for future AOP applicants to improve the pharmaceutical compound treatment by providing a deeper understanding of the role of the parameters. In addition, the proper application of physicochemical parameters in AOP systems acts to track the sustainable development goals (SDGs).
Fulltext Re-irradiation Using Stereotactic Radiotherapy: A Bibliometric Analysis of Research Trends

Mohamed Yoosuf AB, Ajmal Khan M, Abdul Aziz MZ, Mansor S, Appalanaido GK, Alshehri S, et al.

Cureus, 2023 May;15(5):e39600.
PMID: 37384098 DOI: 10.7759/cureus.39600

The objective of this research is to conduct a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) to examine the current research topics and trends pertaining to stereotactic-based re-irradiation. A bibliometric search was conducted for re-irradiation-related literature published in English from the WoSCC database from 1991 to 2022, using VOSviewer to visualize the results. The extracted information comprises the publication year, overall citation count, average citation rate, keywords, and research domains. We conducted a literature review to identify trends in research on re-irradiation. A total of 19,891 citations were found in 924 qualifying papers that came from 48 different nations. The number of publications and citations has grown steadily since 2008 with the highest number of publications in the year 2018. Similarly, a substantial increase in the number of citations has increased since 2004 and the citation growth rate has been positive between 2004 and 2019 with a peak in 2013. The top authorship patterns were six authors (111 publications and 2498 citations), whereas the highest number of citations per publication was attained with an authorship pattern of 17 authors (C/P = 41.1). The collaboration patterns analysis showed that the largest proportion of publications emanated from the United States with 363 publications (30.9%), followed by Germany with 102 publications (8.7%), and France with 92 publications (7.8%). The majority of the analyzed studies were focused on the brain (30%), head and neck (13%), lung (12%), and spine (10%) and there have been emerging studies on the use of re-irradiation for lung, prostate, pelvic and liver utilizing stereotactic radiotherapy. The main areas of interest have changed over time and are now based on a multidisciplinary approach that integrates advanced imaging techniques, stereotactic treatment delivery, the toxicity of organs at risk, quality of life, and treatment outcomes.
Effectiveness of Robotic Stereotactic Radiotherapy in Patients Undergoing Re-irradiation: A Review

Mohamed Yoosuf AB, Alshehri S, Abdul Aziz MZ, Mansor S, Appalanaido GK, Alqathami M

Cureus, 2023 Aug;15(8):e43500.
PMID: 37719625 DOI: 10.7759/cureus.43500

Stereotactic ablative radiotherapy (SABR) is a possible treatment option for patients who develop recurrence within or at the edge of a previously irradiated volume. Robotic stereotactic radiotherapy is the result of technological advances in robotic precision, real-time imaging, non-invasive, highly customizable treatment plan, and delivery with sub-millimeter accuracy. This article reviews the radiobiologic, technical, and clinical aspects of robotic-based SABR re-irradiation for various anatomical sites. An extensive literature search was performed to identify articles on the utilization of robotic stereotactic radiotherapy for patients undergoing re-irradiation. The reported prescription dose and fractionation data along with outcomes such as overall survival, local control rates, and toxicities were qualitatively reviewed. The findings consistently indicate that re-irradiation using robotic SABR provides encouraging survival rates with minimal toxicity in the clinical setting of various anatomical sites delivered using locally non-invasive means where other treatment options are scarce.
Fulltext Short-Term Versus Long-Term Systemic Corticosteroid Use in the Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients

Alshehri S, Alalawi M, Makeen A, Jad A, Alhuwaysi A, Alageeli M, et al.

Malays J Med Sci, 2021 Feb;28(1):59-65.
PMID: 33679221 DOI: 10.21315/mjms2021.28.1.8

Background: The administration of systemic corticosteroids in chronic obstructive pulmonary disease (COPD) exacerbation is the first line of management. The duration of this administration, however, is not well established in clinical practice. The objective of this study is to compare the clinical outcomes between short-term and long-term corticosteroid use in the acute exacerbation of COPD patients.
Methods: A single-centre, retrospective cohort study was conducted. From 2014 to 2018, all patients over 40 years old with COPD who were admitted to the hospital with a case of COPD exacerbation and received systemic corticosteroids at presentation were included. The subjects were divided into two groups according to the duration of systemic corticosteroid therapy. The primary outcome was hospital re-admission within 180 days. The secondary outcomes were 30 days mortality and length of hospitalisation. The two groups were compared using an independent sample t-test, a Chi-square test, and a Mann-Whitney U test, according to the data type.
Results: Eighty patients met the inclusion criteria. A total of 52 (65%) patients completed long-term therapy, while 28 (35%) patients were on short-term treatment. A total of 15 (28.8%) patients reached the primary endpoint in the long-term treatment group versus 19 (67.9%) in the short-term treatment group (P = 0.001). The 30-day mortality was 4 (7.7%) and 0 (0%), respectively, and the median length of hospitalisation was 6.5 and 7.5 days in the long-term group and short-term group, respectively (P = 0.32, P = 0.88).
Conclusion: Long-term corticosteroid use in the management of acute COPD exacerbation was significantly associated with fewer 180 days re-admission. The duration of corticosteroid use remains controversial, and further studies are recommended to assess the relationship between patient profile and adherence to therapy post-discharge with re-exacerbation.
Promises of Molecular Pharmaceutics in the Development of Novel Drug Delivery Formulations

Kumar P, Chaudhary B, Jain V, Baboota S, Shivanandy P, Alharbi KS, et al.

Curr Drug Deliv, 2023;20(9):1262-1274.
PMID: 36380413 DOI: 10.2174/1567201820666221114113637

Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics.
Fulltext Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer

Md S, Alhakamy NA, Neamatallah T, Alshehri S, Mujtaba MA, Riadi Y, et al.

Gels, 2021 Nov 24;7(4).
PMID: 34842729 DOI: 10.3390/gels7040230

The aim of this study was to prepare and evaluate α-mangostin-loaded polymeric nanoparticle gel (α-MNG-PLGA) formulation to enhance α-mangostin delivery in an epidermal carcinoma. The poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were developed using the emulsion-diffusion-evaporation technique with a 3-level 3-factor Box-Behnken design. The NPs were characterized and evaluated for particle size distribution, zeta potential (mV), drug release, and skin permeation. The formulated PLGA NPs were converted into a preformed carbopol gel base and were further evaluated for texture analysis, the cytotoxic effect of PLGA NPs against B16-F10 melanoma cells, and in vitro radical scavenging activity. The nanoscale particles were spherical, consistent, and average in size (168.06 ± 17.02 nm), with an entrapment efficiency (EE) of 84.26 ± 8.23% and a zeta potential of -25.3 ± 7.1 mV. Their drug release percentages in phosphate-buffered solution (PBS) at pH 7.4 and pH 6.5 were 87.07 ± 6.95% and 89.50 ± 9.50%, respectively. The release of α-MNG from NPs in vitro demonstrated that the biphasic release system, namely, immediate release in the initial phase, was accompanied by sustained drug release. The texture study of the developed α-MNG-PLGA NPs gel revealed its characteristics, including viscosity, hardness, consistency, and cohesiveness. The drug flux from α-MNG-PLGA NPs gel and α-MNG gel was 79.32 ± 7.91 and 16.88 ± 7.18 µg/cm2/h in 24 h, respectively. The confocal study showed that α-MNG-PLGA NPs penetrated up to 230.02 µm deep into the skin layer compared to 15.21 µm by dye solution. MTT assay and radical scavenging potential indicated that α-MNG-PLGA NPs gel had a significant cytotoxic effect and antioxidant effect compared to α-MNG gel (p < 0.05). Thus, using the developed α-MNG-PLGA in treating skin cancer could be a promising approach.
New biologically dynamic hybrid pharmacophore triazinoindole-based-thiadiazole as potent α-glucosidase inhibitors: In vitro and in silico study

Khan AA, Rahim F, Taha M, Rehman W, Iqbal N, Wadood A, et al.

Int J Biol Macromol, 2022 Feb 28;199:77-85.
PMID: 34968547 DOI: 10.1016/j.ijbiomac.2021.12.147

Triazinoindole bearing thiadiazole derivatives (1-25) have been synthesized and characterized through different spectroscopic techniques such as 1H, 13C-NMR and HREI-MS. The purpose of the study was to investigate the anti-diabetic activity of the synthesized triazinoindole bearing thiadiazole derivatives by inhibition of α-glucosidase. All synthesized analogues showed outstanding inhibition of α-glucosidase enzyme with IC50 values ranging from 2.5 ± 0.10 to 38.10 ± 0.10 µM as compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Analogue 4 (IC50 = 2.5 ± 0.10 µM) was identifies as the most potent analogue in the series with fifteen folds more active than standard acarbose. Structure activity relationship (SAR) studies suggested that α-glucosidase activities of triazinoindole bearing thiadiazole are primarily dependent upon on number and position of different substitutions present on phenyl parts. Molecular docking study were conducted of the optimized compounds (i.e., compound 4, 6, and 3 etc. using MOE default parameters), the results revealed that compound 4, 6, and 3 showed numerous key interactions with the target protein, which indicate the high potential of these compounds against the target compound. All these compounds were screened for cytotoxic activity against normal normal Vero cell line and found non-toxic.
Role of Flavonoids in Management of Various Biological Targets in Alzheimer's Disease: Evidence from Preclinical to Clinical Studies

Alharbi KS, Javed Shaikh MA, Imam SS, Alshehri S, Ghoneim MM, Almalki WH, et al.

Curr Med Chem, 2023;30(18):2061-2074.
PMID: 36415096 DOI: 10.2174/0929867330666221122115212

More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aβ42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis.
Fulltext Recent Developments in Diagnosis of Epilepsy: Scope of MicroRNA and Technological Advancements

Bandopadhyay R, Singh T, Ghoneim MM, Alshehri S, Angelopoulou E, Paudel YN, et al.

Biology (Basel), 2021 Oct 25;10(11).
PMID: 34827090 DOI: 10.3390/biology10111097

Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, resulting from abnormally synchronized episodic neuronal discharges. Around 70 million people worldwide are suffering from epilepsy. The available antiepileptic medications are capable of controlling seizures in around 60-70% of patients, while the rest remain refractory. Poor seizure control is often associated with neuro-psychiatric comorbidities, mainly including memory impairment, depression, psychosis, neurodegeneration, motor impairment, neuroendocrine dysfunction, etc., resulting in poor prognosis. Effective treatment relies on early and correct detection of epileptic foci. Although there are currently a few well-established diagnostic techniques for epilepsy, they lack accuracy and cannot be applied to patients who are unsupportive or harbor metallic implants. Since a single test result from one of these techniques does not provide complete information about the epileptic foci, it is necessary to develop novel diagnostic tools. Herein, we provide a comprehensive overview of the current diagnostic tools of epilepsy, including electroencephalography (EEG) as well as structural and functional neuroimaging. We further discuss recent trends and advances in the diagnosis of epilepsy that will enable more effective diagnosis and clinical management of patients.
PI3K/Akt/mTOR Pathways Inhibitors with Potential Prospects in Non-Small-Cell Lung Cancer

Alharbi KS, Shaikh MAJ, Almalki WH, Kazmi I, Al-Abbasi FA, Alzarea SI, et al.

J Environ Pathol Toxicol Oncol, 2022;41(4):85-102.
PMID: 36374963 DOI: 10.1615/JEnvironPatholToxicolOncol.2022042281

Lung cancer is the leading cause of cancer-related mortality across the globe. The most prevalent pathological form of lung cancer is non-small-cell lung cancer (NSCLC). Elevated stimulation of the PI3K/Akt/mTOR pathway causes a slew of cancer-related symptoms, making it a promising target for new anticancer drugs. The PI3K/Akt/mTOR path is involved extensively in carcinogenesis and disease advancement in NSCLC. Several new inhibitors targeting this pathway have been discovered in preclinical investigations and clinical trials. The etiology and epidemiology of NSCLC and biology of the PI3K/Akt/mTOR cascade and its role in NSCLC pathogenesis have all been discussed in this article. In this article, we've reviewed PI3K/Akt/mTOR cascade inhibitors that have been proven in vitro and in preclinical trials to be effective in NSCLC. Drugs targeting the PI3K/Akt/mTOR path in the treatment of NSCLC were also addressed. A better knowledge of the underlying molecular biology, including epigenetic changes, is also critical to detecting relevant biomarkers and guiding combination methods. Additionally, improved clinical trial designs will increase the capacity to test novel drugs and combinations for accounting for genomic variation and eventually improve patient outcomes.

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