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Aim/Background: Peripheral Arterial Disease (PAD) affects the lower limbs. Globally there is a growing disease burden among the patients suffering from cardio-vascular disease and metabolic disorders. The purpose of this review is to generate evidence on the efficacy of CAM therapies in PAD. Materials and Methods: This systematic review was performed across the five electronic databases i.e. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid SP, ISI Web of Science, Elsevier Science Direct, and Wiley Online Library as per the PRISMA guidelines from inception till April 2022. Results: After screening n=55,410 articles, n=77 articles were found to fulfill the eligibility criteria and were selected for this review. The nature of interventions investigated in the clinical trials were physical interventions including exercises of different forms, oral supplements, and other interventions such as chelation therapy, Tai Chi Chuan (TCC), Intermittent Mechanical Compression (IMC) device, connective tissue reflex massage, Remote Ischemic Preconditioning (RIC), Transcutaneous Electrical Nerve Stimulation (TENS) and heat therapy. Upon final assessment, it was revealed that physical activity had a positive effect on peripheral arterial disease patients' quality of life. In addition, Ginkgo biloba and nitrate supplements were found effective for Intermittent Claudication (IC) and PAD patients. Conclusion: This review suggests a positive impact of physical activity on peripheral arterial disease patients' quality of life. Evidence also shows that Physical activity/exercise-based intervention alone or in combination with the supplement is found to be effective among PAD patients and has shown significant results in intermittent claudication. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the adverse events (AEs) associated with moxifloxacin (MFX) use in children below the age of 18 years. Methods: This review was performed in conformity with the preferred items for systematic reviews and meta-analysis (PRISMA) guidelines using different databases. Articles meeting the inclusion criteria were screened and the studies were selected for the qualitative synthesis. Results: A total of 21 studies were included in the systematic review. Among these, 7 retrospective cohort studies, 6 case reports, 3 prospective cohort studies, 2 randomized clinical trials (RCT) and the remainder utilized other methodologies. The variability in studies allowed for an assessment of the safety and tolerability of both short-term and long-term MFX administration in pediatric patients. Conclusion: Although MFX use is associated with AEs, the majority were mild and resolved on their own. The reason for QTc prolongation and elevated liver enzymes remain a question for clinicians in prescribing MFX in pediatric patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections. [ABSTRACT FROM AUTHOR]

On a global scale, lung cancer is acknowledged to be the major driver of cancer death attributable to treatment challenges and poor prognosis. Classical cancer treatment regimens, such as chemotherapy or radiotherapy, can be used to treat lung cancer, but the appended adverse effects limit them. Because of the numerous side effects associated with these treatment modalities, it is crucial to strive to develop novel and better strategies for managing lung cancer. Attributes such as enhanced bioavailability, better in vivo stability, intestinal absorption pattern, solubility, prolonged and targeted distribution, and the superior therapeutic effectiveness of numerous anticancer drugs have all been boosted with the emergence of nano-based therapeutic systems. Lipid-based polymeric and inorganic nano-formulations are now being explored for the targeted delivery of chemotherapeutics for lung cancer treatment. Nano-based approaches are pioneering the route for primary and metastatic lung cancer diagnosis and treatment. The implementation and development of innovative nanocarriers for drug administration, particularly for developing cancer therapies, is an intriguing and challenging task in the scientific domain. The current article provides an overview of the delivery methods, such as passive and active targeting for chemotherapeutics to treat lung cancer. Combinatorial drug therapy and techniques to overcome drug resistance in lung cancer cells, as potential ways to increase treatment effectiveness, are also discussed. In addition, the clinical studies of the potential therapies at different stages and the associated challenges are also presented. A summary of patent literature has also been included to keep readers aware of the new and innovative nanotechnology-based ways to treat lung cancer. [ABSTRACT FROM AUTHOR]

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022. [ABSTRACT FROM AUTHOR]

Simple Summary: Nanotechnology has been implemented in healthcare more and more over the past few decades, particularly in applications for more efficacious and safer targeted delivery, detection, and therapy. Topotecan-loaded nanocarrier systems have shown superior pharmacokinetics, biocompatibility, tumor-targeting ability, and stability compared to topotecan in its native form. Additionally, they play a key role in reducing systemic toxicity and battling drug resistance. These advantages enable the widespread use of nano-based systems in various applications. This article explores nanoenabled active and passive targeting strategies and combinatorial therapy employing topotecan to ameliorate various cancers, along with a glimpse of the clinical studies utilizing the said molecule. Chemotherapy has been the predominant treatment modality for cancer patients, but its overall performance is still modest. Difficulty in penetration of tumor tissues, a toxic profile in high doses, multidrug resistance in an array of tumor types, and the differential architecture of tumor cells as they grow are some of the bottlenecks associated with the clinical usage of chemotherapeutics. Recent advances in tumor biology understanding and the emergence of novel targeted drug delivery tools leveraging various nanosystems offer hope for developing effective cancer treatments. Topotecan is a topoisomerase I inhibitor that stabilizes the transient TOPO I-DNA cleavable complex, leading to single-stranded breaks in DNA. Due to its novel mechanism of action, TOPO is reported to be active against various carcinomas, namely small cell lung cancer, cervical cancer, breast cancer, and ovarian cancer. Issues of cross-resistance with numerous drugs, rapid conversion to its inactive form in biological systems, appended adverse effects, and higher water solubility limit its therapeutic efficacy in clinical settings. Topotecan nanoformulations offer several benefits for enhancing the therapeutic action of this significant class of chemotherapeutics. The likelihood that the target cancer cells will be exposed to the chemotherapeutic drug while in the drug-sensitive s-phase is increased due to the slow and sustained release of the chemotherapeutic, which could provide for a sustained duration of exposure of the target cancer cells to the bioavailable drug and result in the desired therapeutic outcome. This article explores nanoenabled active and passive targeting strategies and combinatorial therapy employing topotecan to ameliorate various cancers, along with a glimpse of the clinical studies utilizing the said molecule. [ABSTRACT FROM AUTHOR]

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. Nigella sativa L. (NS) is an important medicinal plant of Islamic value. This review highlights the anti-COVID-19 potential, clinical trials, inventions, and patent literature related to NS and its major chemical constituents, like thymoquinone. The literature was collected from different databases, including Pubmed, Espacenet, and Patentscope. The literature supports the efficacy of NS, NS oil (NSO), and its chemical constituents against COVID-19. The clinical data imply that NS and NSO can prevent and treat COVID-19 patients with a faster recovery rate. Several inventions comprising NS and NSO have been claimed in patent applications to prevent/treat COVID-19. The patent literature cites NS as an immunomodulator, antioxidant, anti-inflammatory, a source of anti-SARS-CoV-2 compounds, and a plant having protective effects on the lungs. The available facts indicate that NS, NSO, and its various compositions have all the attributes to be used as a promising remedy to prevent, manage, and treat COVID-19 among high-risk people as well as for the therapy of COVID-19 patients of all age groups as a monotherapy or a combination therapy. Many compositions of NS in combination with countless medicinal herbs and medicines are still unexplored. Accordingly, the authors foresee a bright scope in developing NS-based anti-COVID-19 composition for clinical use in the future. [ABSTRACT FROM AUTHOR]

Background. Coronavirus infection (COVID-19) has resulted in an unprecedented number of human deaths and economic losses. Analyzing the role of disease in different groups of people is useful for determining the burden of disease. As a result, the purpose of this study was to investigate the influence of COVID-19 on the Saudi Arabian population's quality of life, with a particular emphasis on the likely fall in their life expectancy. Methods. A cross-sectional and retrospective analysis of 2,988 patients' databases was performed to assess COVID-19-induced mortality and complications in the community. The data was gathered from official websites that track the disease's impact daily between July and October 2021. On the acquired data, disability-adjusted life years (DALYs) and relative risk analysis were performed. The data was statistically analyzed using SPSS IBM 25. The Pearson's correlation test was used to examine the relationship between age and disease impact. The significance of the findings was determined by using a P value of less than 0.05. Results. The data from the study indicated that the positive test rate, infection rate, and mortality rate in the population were 1.84% [+0.11/-0.39 of 95% confidence interval (CI)], 1.54% (+0.38/-0.52 of CI), and 1.59% (+0.4/-0.7 of CI), respectively. Highest percentage of mortality was observed in Riyadh (17%), followed by Jeddah (8.7%) and Makkah (7.5%). The DALYs/100,000 inhabitants increased progressively as the age of the population increased, and the highest value was found for those over 70 years old (25.73 ± 2.09). Similarly, the risk outcome (55%) increased significantly (p = 0.037) from 40 years onwards, and the maximum was observed at above 70 years (184%, p = 0.006). The correlation analysis indicated a significant association (p = 0.032) between age and COVID-19 induced mortality from the 40-year-old population onwards. Conclusion. The current study found that the COVID-19 load in Saudi Arabia was comparable to that in nations that were said to have performed well during the pandemic. DALYs increased from 40 years to 60 years, although people over 60 years had a lower life expectancy and were more susceptible to infection. After 60 years, the occurrence of numerous co-morbid illnesses may have added to the population's burden of COVID-19. Further research in this area may yield a more precise estimate of the COVID-19-induced burden on the entire population. [ABSTRACT FROM AUTHOR]

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is the only human paracaspase, that serves as an adaptor protein and controls substantial genes expressed in the activation, proliferation of lymphocyte, and immune reactions by triggering the IKK/NF-kB signaling pathway. However, unusual MALT1-mediated NF-kB signaling pathway has been identified in multiple diseases like cancer, therefore making MALT1 a promising therapeutic target. There are scanty numbers of MALT1 inhibitors, thus the need to discover more compounds with less or no toxicity issue, that are cheap and pharmacologically efficient is of pertinence. Hence, our present study was to identify phyto-small molecules that could bind the allosteric interface of MALT1 using in silico methods. Total of 34 plant molecules were selected and screened for druglikeness, after which they were docked via Maestro 11.1 against the allosteric site of MALT1. The molecule with a binding score (kcal/mol) better than the control drug was subjected to molecular dynamics (MD) simulations of 100 ns via Desmond, free energy perturbations, principal component and Pearson correlation analyses. Our findings from this computational study presents cyanidin (-8.822 kcal/mol) as better binder to the allosteric site of MALT1 based on the molecular docking and pharmacokinetic profiling than thioridazine. Similarly, cyanidin-MALT1 complex showed significant stability and exhibiting contacts with critical amino acid residues in the site of interest than thioridazine-MALT1 complex. Hence, cyanidin is a potential allosteric inhibitor of MALT1. However, an urgent need for in vitro and in vivo validations is required to ascertain the efficacy of cyanidin in the fight against cancer and other MALT1-related diseases.

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase. Despite advancements in tyrosine kinase inhibitors, challenges such as efficacy, safety concerns, and recurring drug resistance persist. This study aims to discover potential c-Abl kinase inhibitors from plant compounds with anti-leukemic properties, employing drug-likeness assessment, molecular docking, in silico pharmacokinetics (ADMET) screening, density function theory (DFT), and molecular dynamics simulations (MDS). Out of 58 screened compounds for drug-likeness, 44 were docked against c-Abl kinase. The top hit compound (isovitexin) and nilotinib (control drug) were subjected to rigorous analyses, including ADMET profiling, DFT evaluation, and MDS for 100 ns. Isovitexin demonstrated a notable binding affinity (-15.492 kcal/mol), closely comparable to nilotinib (-16.826 kcal/mol), showcasing a similar binding pose and superior structural stability and reactivity. While these findings suggest isovitexin as a potential c-Abl kinase inhibitor, further validation through urgent in vitro and in vivo experiments is imperative. This research holds promise for providing an alternative avenue to address existing CML treatment and management challenges.Communicated by Ramaswamy H. Sarma.

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)