Naegleria fowleri, a thermophilic flagellate amoeba known as a “brain‐eating” amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%–99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3–7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact‐independent (brain damage through different proteins) and contact‐dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life‐threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder.
Urinary tract infection (UTI) is one of the most severe public health problem affecting both sexes but females are more susceptible due to the differences in urogenital and reproductive anatomy, physiology and lifestyle. As in UTI, different parts of the urinary tract are affected and morbidity due to UTI is more common in women of all ages and older men. Due to multi-drug resistant strains and high recurrence rate, UTI has become a major socioeconomic burden. The current review article was aimed to describe the natural therapeutic strategies to manage and cure the UTI. For this purpose, different databases including Google Scholar, Cochrane database, and PubMed etc. were explored. Inclusion criteria were any research article investigating the current therapy of UTI. It was found that microbial infections including Escherichia coli, Enterococcus faecalis and Klebsiella species are the major causes of UTI with different signs and symptoms including painful urination or dysuria, hematuria, urinary urgency, burning micturition, frequent urination, nausea, and vomiting. Antibiotics like trimethoprim, sulfamethoxazole, quinolone etc. as the first choice of the drug are used worldwide. However, due to microbial resistance, several life-threatening side effects, repeated high doses, high cost and low efficacy of these antibiotics motivated the researchers to explore natural remedies for the treatment of UTI. Herbal medicines are effective to combat bacterial resistance with high efficacy, and easy availability with minimal or no side effects. For these reasons it has attained the attention of researchers wanting to explore the herbal treatment of UTI. Vaccinium macrocarpon, Tribulus terrestris, Trachyspermum copticum, Cinnamomum verum and Hybanthusenn easpermus are some common medicinal plants reported to have therapeutic potential for the management and cure of the UTI. Although herbal medicines have more potential over conventional medicine but more discoveries are required to explore the phytoconstituents and their mechanism of action responsible for the management and cure of UTI.
In this article, we have discussed current progress in the understanding of the epidemiology, clinical manifestations, pathogenesis and management strategies of the disease.
The plants belonging to the genus Vicia are of great interest as a source of many bioactive compounds and micronutrients. A snapshot of their cultivation, habitat, main components, from which essential oils can be obtained, is given. The traditional medicinal uses of Vicia plants are also reported, as well as the wide spectrum of the main biological activities attributed to Vicia plants is discussed regarding potential health beneficial properties, in particular anti‐Parkinson, anticholinesterase, antidepressant, anticonvulsant, antimicrobial, cytotoxic, antioxidant, antiinflammatory and antinociceptive, antidiabetic, antihemolytic, anticoagulant, estrogenic, diuretic, antihypoxic activities.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key targets for atherosclerosis drug development as its binding with low-density lipoprotein receptor leads to atherosclerosis. The protein-ligand interaction helps to understand the actual mechanism for the pharmacological action. This research aims to discover the best inhibitory candidates targeting PCSK9. To start with, reported ACE inhibitors were incorporated into pharmacophore designing using PharmaGist to produce pharmacophore models. Selected models were later screened against the ZINC database using ZINCPHARMER to define potential drug candidates that were docked with the target protein to understand their interactions. Molecular docking revealed the top 10 drug candidates against PCSK9, with binding energies ranging from -9.8 kcal·mol-1 to -8.2 kcal·mol-1, which were analyzed for their pharmacokinetic properties and oral bioavailability. Some compounds were identified as plant-derived compounds like (S)-canadine, hesperetin or labetalol (an antihypertensive drug). Molecular dynamics results showed that these substances formed stable protein-ligand complexes. (S)-canadine-PCSK9 complex was the most stable with the lowest RMSD. It was concluded that (S)-canadine may act as a potential inhibitor against atherosclerosis for the development of new PCSK9 inhibitory drugs in future in vitro research.
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