Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit.

Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.

Discovering potential inhibitors of Raf proto-oncogene serine/threonine kinase 1: a virtual screening approach towards anticancer drug development.

Raf proto-oncogene serine/threonine kinase 1 (RAF1 or c-Raf) is a serine/threonine protein kinase crucial in regulating cell growth, differentiation, and survival. Any disruption or overexpression of RAF1 can result in neoplastic transformation and other disorders such as cardiomyopathy, Noonan syndrome, leopard syndrome, etc. RAF1 has been identified as a potential therapeutic target in drug development against various complex diseases, including cancer, due to its remarkable role in disease progression. Here, we carried out a multitier virtual screening study involving different in-silico approaches to discover potential inhibitors of RAF1. After applying the Lipinski rule of five, we retrieved all phytocompounds from the IMPPAT database based on their physicochemical properties. We performed a molecular docking-based virtual screening and got top hits with the best binding affinity and ligand efficiency. Then we screened out the selected hits using the PAINS filter, ADMET properties, and other druglike features. Eventually, PASS evaluation identifies two phytocompounds, Moracin C and Tectochrysin, with appreciable anti-cancerous properties. Finally, all-atom molecular dynamics simulation (MDS) followed by interaction analysis was performed on the elucidated compounds in complex with RAF1 for 200 ns to investigate their time-evolution dynamics and interaction mechanism. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and Dynamical Cross-Correlation Matrix (DCCM) analyses then followed these results from the simulated trajectories. According to the results, the elucidated compounds stabilize the RAF1 structure and lead to fewer conformational alterations. The results of the current study indicated that Moracin C and Tectochrysin could serve as potential inhibitors of RAF1 after required validation.Communicated by Ramaswamy H. Sarma.

Identification of mitogen-activated protein kinase 7 inhibitors from natural products: Combined virtual screening and dynamic simulation studies.

Mitogen-activated protein kinase 7 (MAPK7) is a serine/threonine protein kinase that belongs to the MAPK family and plays a vital role in various cellular processes such as cell proliferation, differentiation, gene transcription, apoptosis, metabolism, and cell survival. The elevated expression of MAPK7 has been associated with the onset and progression of multiple aggressive tumors in humans, underscoring the potential of targeting MAPK7 pathways in therapeutic research. This pursuit holds promise for the advancement of anticancer drug development by developing potential MAPK7 inhibitors. To look for potential MAPK7 inhibitors, we exploited structure-based virtual screening of natural products from the ZINC database. First, the Lipinski rule of five criteria was used to filter a large library of ~90,000 natural compounds, followed by ADMET and pan-assay interference compounds (PAINS) filters. Then, top hits were chosen based on their strong binding affinity as determined by molecular docking. Further, interaction analysis was performed to find effective and specific compounds that can precisely bind to the binding pocket of MAPK7. Consequently, two compounds, ZINC12296700 and ZINC02123081, exhibited significant binding affinity and demonstrated excellent drug-like properties. All-atom molecular dynamics simulations for 200 ns confirmed the stability of MAPK7-ZINC12296700 and MAPK7-ZINC02123081 docked complexes. According to the molecular mechanics Poisson-Boltzmann surface area investigation, the binding affinities of both complexes were considerable. Overall, the result suggests that ZINC12296700 and ZINC02123081 might be used as promising leads to develop novel MAPK7 inhibitors. Since these compounds would interfere with the kinase activity of MAPK7, therefore, may be implemented to control cell growth and proliferation in cancer after required validations.

Exploring the potential of phytochemicals as inhibitors of 3'-phosphoadenosine 5'-phosphosulfate synthase 1 targeting cancer therapy.

3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is an enzyme that critically synthesises the biologically active form of sulfate (PAPS) for all sulfation reactions. The discovery of PAPSS1 as a possible drug target for cancer therapy, specifically in non-small cell lung cancer, has prompted us to investigate potential small-molecule inhibitors of PAPSS1. Here, a structure-based virtual screening method was used to search for phytochemicals in the IMPPAT database to find potential inhibitors of PAPSS1. The primary hits were selected based on their physicochemical, ADMET, and drug-like properties. Then, the binding affinities were calculated and analyzed the interactions to identify safer and more effective hits. The research identified two phytochemicals, Guggulsterone and Corylin, that exhibited significant affinity and specific interaction with the ATP-binding pocket of PAPSS1. Structural observations made by molecular docking were further accompanied by molecular dynamics (MD) simulations and principal component analysis (PCA) to examine the conformational changes and stability of PAPSS1 with the elucidated compounds Guggulsterone and Corylin. MD simulation results suggested that the binding of Guggulsterone and Corylin stabilizes the PAPSS1 structure, leading to fewer conformational changes. This implies that these compounds may be useful in developing PAPSS1 inhibitors for the therapeutic development against non-small cell lung cancer (NSCLC). This study highlights the potential of phytochemicals as PAPSS1 inhibitors and the utility of computational approaches in drug discovery.Communicated by Ramaswamy H. Sarma.

Antimicrobial, Anticancer, and Antioxidant Activities of Maize and Clover Pollen Grains Extracts: A Comparative Study with Phytochemical Characterizations.

The failure to treat infectious diseases due to the continual emergence of drug-resistant microbes poses a huge and serious challenge for human health globally. Currently, the discovery and development of natural therapeutic compounds are attracting considerable attention from researchers worldwide. In this project, two types of pollen grains (maize and clover) were evaluated for potential antimicrobial activities. Extracts of both pollen grains were purified using HPLC, which has been shown to have numerous phenolic and flavonoid compounds. Pyro catechol and methyl gallate were detected in high concentrations (1145.56 and 1056.57 µg/mL, respectively) in the maize extract, while caffeic acid, quercetin, and kaempferol (464.73, 393.05, and 390.93 µg/mL, respectively) were among the compounds observed at high concentrations in the clover pollen grains extract. Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Candida albicans were more sensitive to the clover pollen grains extract with inhibition zones of 22 ± 0.2, 18 ± 0.1, 29 ± 0.3, and 42 ± 0.4 mm compared to the size of the inhibitory zones caused by the maize pollen grains extract (19 ± 0.3, 15 ± 0.4, 27 ± 0.1, and 22 ± 0.4 mm, respectively). Moreover, lower MIC values for the clover pollen grains extract were recorded against C. albicans (1.97 ± 0.04 µg/mL), S. aureus (62.5 ± 1.00 µg/mL), and E. coli (62.5 ± 0.07 µg/mL) than the MICs caused by the maize pollen grains extract. The use of a transmission electron microscope revealed that the E. coli that had been treated with the clover pollen grains extract showed changes in its cell walls compared to that treated with the maize pollen grains extract. The clover pollen grains extract exhibited a stronger antioxidant potential, with an IC50 value of 22.18 µg/mL, compared to an IC50 value of 54.85 µg/mL for the maize pollen grains extract, via a DPPH scavenging assay. Regarding anticancer activity, the maize pollen grains extract was revealed to be more effective in terms of inhibiting the human colon cancer cell line HCT-116, with an IC50 value of 67.02 ± 1.37 µg/mL, compared with the observed toxicity caused by the clover extract, with an IC50 value of 75.03 ± 1.02 µg/mL. Overall, the clover pollen grains extract demonstrated potent antibacterial and antioxidant activities, but not anticancer activity, when compared to the maize grains extract. Thus, the current findings related to both types of pollen grains (clover and maize) highlight their potential therapeutic applications for the treatment of certain infectious diseases and malignancies.

Antioxidative and ROS-dependent apoptotic effects of Cuscuta reflexa Roxb. stem against human lung cancer: network pharmacology and in vitro experimental validation.

Lung cancer remains a formidable global health challenge, necessitating the exploration of novel therapeutic approaches. This study investigates the potential of Cuscuta reflexa Roxb. stem extract as an anticancer agent against human lung cancer, focusing on its antioxidative and ROS-dependent apoptotic effects. Utilizing a combination of network pharmacology and in-vitro experimental validation, we delineate the multifaceted molecular mechanisms underlying the observed effects. The antioxidant potential of C. reflexa stem extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS•+) and ferric reducing/antioxidant power (FRAP), hydroxyl free radical scavenging, reactive nitrogen oxide scavenging and super oxide anion radical scavenging assays. Furthermore, the antiproliferative and proapoptotic effect of C. reflexa stem extract was evaluated against A549 lung adenocarcinoma cell line using the consecrated sulforhodamine B (SBR) and Annexin V-PI assays. Additionally, the mitochondrial membrane potential (MMP) and the total reactive oxygen species (ROS) estimation assays were performed. As a result, network pharmacology analysis revealed a complex interaction network between the bioactive constituents of C. reflexa and key proteins implicated in lung cancer progression. The C. reflexa stem extract showed dose-dependent antioxidant activity against DPPH• (IC50 - 87.38 µg/mL), reactive nitrogen oxide (IC50 - 318.34 µg/mL), FRAP (IC50 - 359.96 µg/mL), hydroxy free radicals (IC50 - 526.12 µg/mL) than ABTS●+ (IC50 - 698.45 µg/mL) and super oxide anion (IC50 - 892.71 µg/mL) as well as cytotoxic activity against A549 cells (IC50 - 436.80 µg/mL). Observations of morphological features in treated cells have revealed hallmark of apoptosis properties. Furthermore, as a result of treatment with C. reflexa stem extract, ROS generation and mitochondrial depolarization were increased in A549 cells, suggesting that this treatment has significant apoptotic properties. . These findings highlight the potential utility of this natural extract as an innovative therapeutic strategy for lung cancer treatment. The integration of network pharmacology and experimental validation enhances our understanding of the underlying mechanisms and provide the way for further translational research.Communicated by Ramaswamy H. Sarma.

Genome-Wide Analysis of Kidney Renal Cell Carcinoma: Exploring Differentially Expressed Genes for Diagnostic and Therapeutic Targets.

Kidney renal cell carcinoma (KIRC) is the most common type of renal cancer. Kidney malignancies have been ranked in the top 10 most frequently occurring cancers. KIRC is a prevalent malignancy with a poor prognosis. The disease has risen for the last 40 years, and robust biomarkers for KIRC are needed for precision/personalized medicine. In this bioinformatics study, we utilized genomic data of KIRC patients from The Cancer Genome Atlas for biomarker discovery. A total of 314 samples were used in this study. We identified many differentially expressed genes (DEGs) categorized as upregulated or downregulated. A protein-protein interaction network for the DEGs was then generated and analyzed using the Search Tool for the Retrieval of Interacting Genes plugin of Cytoscape. A set of 10 hub genes was selected based on the Maximum Clique Centrality score defined by the CytoHubba plugin. The elucidated set of genes, that is, CALCA, CRH, TH, CHAT, SLC18A3, FSHB, MYH6, CAV3, KCNA4, and GBX2, were then categorized as potential candidates to be explored as KIRC biomarkers. The survival analysis plots for each gene suggested that alterations in CHAT, CAV3, CRH, MYH6, SLC18A3, and FSHB resulted in decreased survival of KIRC patients. In all, the results suggest that genomic alterations in selected genes can be explored to inform biomarker discovery and for therapeutic predictions in KIRC.

Identification of novel c-Kit inhibitors from natural sources using virtual screening and molecular dynamics simulations.

The Mast/Stem cell growth factor receptor Kit (c-Kit), a Proto-oncogene c-Kit, is a tyrosine-protein kinase involved in cell differentiation, proliferation, migration, and survival. Its role in developing certain cancers, particularly gastrointestinal stromal tumors (GISTs) and acute myeloid leukemia (AML), makes it an attractive therapeutic target. Several small molecule inhibitors targeting c-Kit have been developed and approved for clinical use. Recent studies have focused on identifying and optimizing natural compounds as c-Kit inhibitors employing virtual screening. Still, drug resistance, off-target side effects, and variability in patient response remain significant challenges. From this perspective, phytochemicals could be an important resource for discovering novel c-Kit inhibitors with less toxicity, improved efficacy, and high specificity. This study aimed to uncover possible c-Kit inhibitors by utilizing a structure-based virtual screening of active phytoconstituents from Indian medicinal plants. Through the screening stages, two promising candidates, Anilinonaphthalene and Licoflavonol, were chosen based on their drug-like features and ability to bind to c-Kit. These chosen candidates were subjected to all-atom molecular dynamics (MD) simulations to evaluate their stability and interaction with c-Kit. The selected compounds Anilinonaphthalene from Daucus carota and Licoflavonol from Glycyrrhiza glabra showed their potential to act as selective binding partners of c-Kit. Our results suggest that the identified phytoconstituents could serve as a starting point to develop novel c-Kit inhibitors for developing new and effective therapies against multiple cancers, including GISTs and AML. The use of virtual screening and MD simulations provides a rational approach to discovering potential drug candidates from natural sources.Communicated by Ramaswamy H. Sarma.

Anticancer properties of sulforaphane: current insights at the molecular level.

Sulforaphane (SFN) is an isothiocyanate with multiple biomedical applications. Sulforaphane can be extracted from the plants of the genus Brassica. However, broccoli sprouts are the chief source of sulforaphane and are 20 to 50 times richer than mature broccoli as they contain 1,153 mg/100 g. SFN is a secondary metabolite that is produced as a result of the hydrolysis of glucoraphanin (a glucosinolate) by the enzyme myrosinase. This review paper aims to summarize and understand the mechanisms behind the anticancer potential of sulforaphane. The data was collected by searching PubMed/MedLine, Scopus, Web of Science, and Google Scholar. This paper concludes that sulforaphane provides cancer protection through the alteration of various epigenetic and non-epigenetic pathways. It is a potent anticancer phytochemical that is safe to consume with minimal side effects. However, there is still a need for further research regarding SFN and the development of a standard dose.

Phytochemical Characterization of Saudi Mint and Its Mediating Effect on the Production of Silver Nanoparticles and Its Antimicrobial and Antioxidant Activities.

The green synthesis of nanoparticles (NPs) is attracting enormous attention as a new area of study that encompasses the development and discovery of new agents for their utilization in different fields, such as pharmaceuticals and food. Nowadays, the use of plants, particularly medicinal plants, for the creation of NPs has emerged as a safe, ecofriendly, rapid, and simple approach. Therefore, the present study aimed to use the Saudi mint plant as a medicinal plant for the synthesis of silver nanoparticles (AgNPs) and to evaluate the antimicrobial and antioxidant activities of AgNPs compared to mint extract (ME). A phenolic and flavonoid analysis that was conducted by using HPLC indicated the presence of numerous compounds in the ME. Through an HPLC analysis, chlorogenic acid at a concentration of 7144.66 µg/mL was the main detected component in the ME, while catechin, gallic acid, naringenin, ellagic acid, rutin, daidzein, cinnamic acid, and hesperetin were identified in varying concentrations. AgNPs were synthesized by using ME and were confirmed via UV-visible spectroscopy at 412 nm of the maximum absorption. The mean diameter of the synthesized AgNPs was measured by TEM to be 17.77 nm. Spectra obtained by using energy-dispersive X-ray spectroscopy indicated that silver was the main element formation in the created AgNPs. The presence of various functional groups, analyzed by using Fourier transform infrared spectroscopy (FTIR), indicated that the mint extract was responsible for reducing Ag+ to Ag0. The spherical structure of the synthesized AgNPs was confirmed by X-ray diffraction (XRD). Furthermore, the ME showed reduced antimicrobial activity (a zone of inhibition of 30, 24, 27, 29, and 22 mm) compared with the synthesized AgNPs (a zone of inhibition of 33, 25, 30, 32, 32, and 27 mm) against B. subtilis, E. faecalis, E. coli, P. vulgaris, and C. albicans, respectively. The minimum inhibitory concentration of the AgNPs was lower than that of the ME for all of the tested micro-organisms, except for P. vulgaris. The MBC/MIC index suggested that the AgNPs revealed a higher bactericidal effect compared to the ME. The synthesized AgNPs exhibited antioxidant activity with a reduced IC50 (IC50 of 8.73 µg/mL) compared to that of the ME (IC50 of 13.42 µg/mL). These findings demonstrate that ME could be applied as a mediator for AgNPs synthesis and natural antimicrobial and antioxidant agents.

The Typical Patterns of Lymphomas in Northwestern Saudi Arabia.

BACKGROUND: Lymphoma is one of the leading cancers in Saudi Arabia. Because there is a paucity of data about the prevalence of lymphomas in Saudi Arabia, numerous extensive investigations are still required. Thus, the present study aimed to assess the common patterns of lymphomas in Northwestern Saudi Arabia. METHODS: This is a retrospective study conducted at the Histopathology Departments of King Khalid and King Salman Hospitals in Hail city, Saudi Arabia, between 2008-2020. The present study comprised 134 lymphoma patients, and all data referring to these patients, such as gender, age, lymphoma type, grade, and cancer site, were retrieved. RESULTS: The most common lymphoma type was NHL, followed by HL, constituting 32.8% and 20%, respectively. There was a clear difference between male and female patients of HL type where the male was higher than the female (24% versus 15.3%). The risk of HL associated with male gender, the relative risk (RR) CI (95% Confidence interval) = 2.0077 (0.9447 - 4.2667), p = 0.0700, z statistic = 1.812. CONCLUSIONS: Lymphoma is prevalent in the Hail region with an exceptionally everincreasing incidence of HL. Wide-ranging lymphoma varieties have been explored in the Hail region, denoting large groups of unattributable etiologic modifiable risk factors.

Proof of concept nanotechnological approach to in vitro targeting of malignant melanoma for enhanced immune checkpoint inhibition.

Immunotherapies, including immune checkpoint inhibitors, have limitations in their effective treatment of malignancies. The immunosuppressive environment associated with the tumor microenvironment may prevent the achievement of optimal outcomes for immune checkpoint inhibitors alone, and nanotechnology-based platforms for delivery of immunotherapeutic agents are increasingly being investigated for their potential to improve the efficacy of immune checkpoint blockade therapy. In this manuscript, nanoparticles were designed with appropriate size and surface characteristics to enhance their retention of payload so that they can transmit their loaded drugs to the tumor. We aimed to enhance immune cell stimulation by a small molecule inhibitor of PD-1/PD-L1 (BMS202) using nanodiamonds (ND). Melanoma cells with different disease stages were exposed to bare NDs, BMS202-NDs or BMS202 alone for 6 h. Following this, melanoma cells were co-cultured with freshly isolated human peripheral blood mononuclear cells (hPBMCs). The effects of this treatment combination on melanoma cells were examined on several biological parameters including cell viability, cell membrane damage, lysosomal mass/pH changes and expression of γHA2X, and caspase 3. Exposing melanoma cells to BMS202-NDs led to a stronger than normal interaction between the hPBMCs and the melanoma cells, with significant anti-proliferative effects. We therefore conclude that melanoma therapy has the potential to be enhanced by non-classical T-cell Immune responses via immune checkpoint inhibitors delivered by nanodiamonds-based nanoparticles.

Signal Transducer and Activator of Transcription 6 Changes and Protein Frustration by Single Amino Acid Substitutions: Implications for Cancer Progression.

Signal transducer and activator of transcription 6 (STAT6) is a multifunctional protein that plays critical functions in cell proliferation, apoptosis, differentiation, and angiogenesis. Mutations in STAT6 may contribute to the development of certain complex diseases such as cancer. This study examined single amino acid substitutions in STAT6 to pinpoint deleterious variants and their related structural and functional impairments. Data on STAT6 mutations were obtained from the Ensembl database and analyzed to evaluate the selected mutations for their pathogenicity and destabilizing or harmful effects. Specifically, we analyzed aggregation propensity, nonpacking density, and accessible surface area on the chosen mutations. The results suggest that seven out of eight mutations are less soluble, which might lead to aggregation, disrupt ordered helices, and alter strand propensity. Four mutations lay in the conserved regions of the protein, as revealed by the Consurf analysis. We found that three mutations, E318G, L365F, and R562H, change hydrophobic contacts and lead to frustration of STAT6, which can alter its stability, contributing to disease progression in cancer. In conclusion, these findings inform how single amino acid changes can destabilize STAT6. This has implications for cancer progression which warrants further experimental research.

Discovering Gummadiol and Isoarboreol as potential inhibitors of sphingosine kinase 1: virtual screening and MD simulation studies.

Sphingosine kinase 1 (SphK1) dysfunction is well-known to be linked to various severe diseases, including breast, lung, prostate, and hematological cancers. Due to its crucial function in the onset of cancer and its progression, it is considered a notable drug target for anticancer therapy. Small molecule inhibitors with high specificity and efficacy towards SphK1 are needed for their therapeutic use. In order to find possible SphK1 inhibitors, we conducted a stepwise structure-based virtual screening of plant-based molecules available from the IMPPAT library. A multi-step virtual screening, including physicochemical and ADMET evaluation, PAINS, molecular docking, PASS analysis followed by molecular dynamics (MD) simulation and principal component analysis, identifies two compounds, Gummadiol and Isoarboreol, against SphK1. All-atom MD simulations were performed for 100 ns which examined the structural changes and stability of the docked complexes in the aqueous environment. The time evolution data of structural deviations and compactness, PCA and free energy landscapes suggested that the binding of Gummadiol and Isoarboreol with SphK1 is considerably stable throughout the trajectory. The study highlighted the use of phytochemicals in anticancer therapeutics and presented Gummadiol and Isoarboreol as promising inhibitors of SphK1.Communicated by Ramaswamy H. Sarma.

Phytochemical Characterization and Efficacy of Artemisia judaica Extract Loaded Chitosan Nanoparticles as Inhibitors of Cancer Proliferation and Microbial Growth.

Despite the advanced development in the field of drug discovery and design, fighting infectious and non-infectious diseases remains a major worldwide heath challenge due to the limited activity of currently used drugs. Nevertheless, in recent years, the approach of designing nanoparticles for therapeutic applications has gained more interest and promise for future use. Thus, the current study is focused on the evaluation of A. judaica extract and chitosan nanoparticles loaded extract (CNPsLE) for potential antimicrobial and anticancer activities. The HPLC analysis of the extract has shown the presence of various phenolic and flavonoid compounds, including kaempferol (3916.34 µg/mL), apigenin (3794.32 µg/mL), chlorogenic acid (1089.58 µg/mL), quercetin (714.97 µg/mL), vanillin (691.55 µg/mL), naringenin (202.14 µg/mL), and rutin (55.64 µg/mL). The extract alone showed higher MIC values against B. subtilis, E. coli, S. aureus, K. pneumonia, and C. albicans (62.5, 15.65, 15.62, 31.25, and 31.25 µg/mL, respectively), whereas lower MIC values were observed when the extract was combined with CNPsLE (0.97, 1.95, 3.9, 4.1, and 15.62 µg/mL, respectively). The extract exhibited low cytotoxicity against normal Vero cells with IC50 173.74 µg/mL in comparison with the cytotoxicity of the CNPsLE (IC50, 73.89 µg/mL). However, CNPsLE showed more selective toxicity against the human prostate cancer cell line (PC3) with IC50 of 20.8 µg/mL than the extract alone with 76.09 µg/mL. In the docking experiments, kaempferol and apigenin were revealed to be suitable inhibitors for prostate cancer (2Q7L). Overall, the obtained data highlighted the promising potential therapeutic use of CNPsLE as an anticancer and antimicrobial agent.

Interventions to Increasing Test Cancellation Rates in Blood Bank Based on a Multi-Year Review.

BACKGROUND: Apart from the wasted resource, canceled tests cause delay of test results thus affecting patient care. The study aimed to identify the reasons for the test cancellation of samples received in a blood bank laboratory and determine the improvement target. METHODS: The study retrospectively reviewed the canceled tests in a blood bank laboratory of a hospital in Hail, Saudi Arabia, from January 2017 to December 2020. Records of the canceled test taken from the quality assurance database were utilized to identify the various reasons. RESULTS: A total of 2,017 (2.7%) test cancellations were recorded in the 4-year study period with increasing rates noted. The two primary reasons were specimen quality issues (61.9%) and problems related to test orders (33.9%). The main reason for test cancellation was clotted specimen (48.5%) followed by incorrect test order (15.6%) and duplicate test order (13.9%). Statistically, a significant difference exists between the annual rates and reasons of cancellation, X2 (6, n = 2,017) = 83.24, p < 0.001. CONCLUSIONS: Test cancellations due to various reasons remain a significant challenge for clinical laboratories. Detailed analyses on these major reasons can aid in displaying an effective approach to decrease the cancellation rates. Harmonization among inter-professional health workers concerning specimen collection and handling, and involving clinical laboratory personnel could minimize laboratory errors and avoid test cancellations.

Statins Use in Alzheimer Disease: Bane or Boon from Frantic Search and Narrative Review.

Alzheimer's disease (AD) was used to describe pre-senile dementia to differentiate it from senile dementia, which develops in the adult age group of more than 65 years. AD is characterized by the deposition of amyloid beta (Aß) plaque and tau-neurofibrillary tangles (TNTs) in the brain. The neuropathological changes in AD are related to the deposition of amyloid plaques, neurofibrillary tangles, and progression of neuroinflammation, neuronal mitochondrial dysfunction, autophagy dysfunction, and cholinergic synaptic dysfunction. Statins are one of the main cornerstone drugs for the management of cardiovascular disorders regardless of dyslipidemia status. Increasing the use of statins, mainly in the elderly groups for primary and secondary prevention of cardiovascular diseases, may affect their cognitive functions. Extensive and prolonged use of statins may affect cognitive functions in healthy subjects and dementia patients. Statins-induced cognitive impairments in both patients and health providers had been reported according to the post-marketing survey. This survey depends mainly on sporadic cases, and no cognitive measures were used. Evidence from prospective and observational studies gives no robust conclusion regarding the beneficial or detrimental effects of statins on cognitive functions in AD patients. Therefore, this study is a narrative review aimed with evidences to the beneficial, detrimental, and neutral effects of statins on AD.

Bacterial Infections among Patients with Chronic Diseases at a Tertiary Care Hospital in Saudi Arabia.

Infections caused by multi-drug-resistant bacteria in patients with chronic diseases have been associated with high mortality and morbidity. While few reports have evaluated bacterial infections in multiple chronic disease patients, the focus of the current study was to investigate the prevalence of bacterial infections and the susceptibility profiles of causative strains among various groups of patients suffering from chronic diseases. Microbiological reports of patients suffering from cancer, diabetes mellitus, cardiovascular diseases, kidney diseases, and skin burns were retrospectively collected from a tertiary hospital in Saudi Arabia. Approximately 54.2% of recruited patients were males, and positive urine was the most prevalent specimen associated with kidney disease patients (25%). Escherichia coli isolates were predominant among cardiovascular, kidney, and cancer patients. Staphylococcus aureus was commonly detected in diabetics and those with burns. Although resistance patterns varied based on the type of specimens and underlying diseases, Escherichia coli showed limited resistance to colistin, carbapenems, and tigecycline, while S. aureus demonstrated susceptibility to ciprofloxacin, gentamicin, and rifampin. These observations are crucial for clinicians and policymakers to ensure effective treatment plans and improve outcomes in these patients with comorbidity.

Analysis of preanalytical errors in a clinical chemistry laboratory: A 2-year study.

Patient safety and medical diagnosis of patients are mainly influenced by laboratory results. The present study aimed to evaluate the errors in the preanalytical phase of testing in a Clinical Chemistry diagnostic laboratory. A review was conducted at the Clinical Chemistry Laboratory of a hospital in Saudi Arabia from January 2019 to December 2020. Using the laboratory information system, the data of all canceled tests and requests were retrieved and evaluated for preanalytical errors. A total of 55,345 laboratory test requests and samples from different departments were evaluated for preanalytical errors. An overall rate of 12.1% (6705) was determined as preanalytical errors. The occurrence of these errors was found to be highest in the emergency department (21%). The leading preanalytical errors were nonreceived samples (3.7%) and hemolysis (3.5%). The annual preanalytical errors revealed an increasing rate in outpatient and inpatient departments, while a decreasing rate was observed in the emergency department. An increased rate of errors was also noted for the 2-year study period from 11.3% to 12.9%. The preanalytical phase has a significant impact on the quality of laboratory results. The rate of error in the study was high and the leading causes were nonreceived samples and hemolysis. An increased occurrence of hemolyzed samples in the outpatient department was noted. Enhanced educational efforts emphasizing specimen quality issues and training in sample collection among hospital staff must be carried out.

Pharmacological Properties of 4', 5, 7-Trihydroxyflavone (Apigenin) and Its Impact on Cell Signaling Pathways.

Plant bioactive compounds, particularly apigenin, have therapeutic potential and functional activities that aid in the prevention of infectious diseases in many mammalian bodies and promote tumor growth inhibition. Apigenin is a flavonoid with low toxicities and numerous bioactive properties due to which it has been considered as a traditional medicine for decades. Apigenin shows synergistic effects in combined treatment with sorafenib in the HepG2 human cell line (HCC) in less time and statistically reduces the viability of tumor cells, migration, gene expression and apoptosis. The combination of anti-cancerous drugs with apigenin has shown health promoting potential against various cancers. It can prevent cell mobility, maintain the cell cycle and stimulate the immune system. Apigenin also suppresses mTOR activity and raises the UVB-induced phagocytosis and reduces the cancerous cell proliferation and growth. It also has a high safety threshold, and active (anti-cancer) doses can be gained by consuming a vegetable and apigenin rich diet. Apigenin also boosted autophagosome formation, decreased cell proliferation and activated autophagy by preventing the activity of the PI3K pathway, specifically in HepG2 cells. This paper provides an updated overview of apigenin's beneficial anti-inflammatory, antibacterial, antiviral, and anticancer effects, making it a step in the right direction for therapeutics. This study also critically analyzed the effect of apigenin on cancer cell signaling pathways including the PI3K/AKT/MTOR, JAK/STAT, NF-κB and ERK/MAPK pathways.