The emerging role of noncoding RNAs in the PI3K/AKT/mTOR signalling pathway in breast cancer.

Breast cancer persists as a major problem for the world's healthcare, thus it is essential to fully understand the complex molecular processes that cause its growth and development. ncRNAs had been discovered to serve critical roles in a variety of cellular functions, including the regulation of signalling pathways. Within different pathways, the AKT/PI3K/mTOR signalling cascade has received a lot of interest because of its role in cancer. A complex interaction between ncRNAs, notably miRNAs, lncRNAs, and circRNAs, and the AKT/PI3K/mTOR signalling pathway exerts both oncogenic and tumor-suppressive activities by targeting critical components of the pathway directly or indirectly. Through miRNA-mediated post-transcriptional regulation, lncRNA-guided chromatin remodelling, and circRNA sequestration, ncRNAs modulate the activity of PI3K, AKT, and mTOR, influencing cell proliferation, survival, and metastasis. Furthermore, ncRNAs can serve as promising biomarkers for breast cancer prognosis, diagnosis, and treatment response, as their dysregulation is commonly observed in breast cancer patients. Harnessing the potential of ncRNAs as therapeutic targets or tools for restoring pathway homeostasis holds promise for innovative treatment strategies in breast cancer. Understanding the intricate regulatory networks orchestrated by ncRNAs in this context may pave the way for novel diagnostic approaches, therapeutic interventions, and a deeper comprehension of breast cancer's molecular landscape, ultimately improving patient outcomes. This abstract underscores the emerging significance of ncRNAs in the AKT/PI3K/mTOR signaling pathway in breast cancer.

Targeting GluR3 in Depression and Alzheimer's Disease: Novel Compounds and Therapeutic Prospects.

BACKGROUND: The present study investigates the interrelated pathophysiology of depression and Alzheimer's disease (AD), with the objective of elucidating common underlying mechanisms. OBJECTIVE: Our objective is to identify previously undiscovered biogenic compounds from the NuBBE database that specifically interact with GluR3. This study examines the bidirectional association between depression and AD, specifically focusing on the role of depression as a risk factor in the onset and progression of the disease. METHODS: In this study, we utilize pharmacokinetics, homology modeling, and molecular docking-based virtual screening techniques to examine the GluR3 AMPA receptor subunit. RESULTS: The compounds, namely ZINC000002558953, ZINC000001228056, ZINC000000187911, ZINC000003954487, and ZINC000002040988, exhibited favorable pharmacokinetic profiles and drug-like characteristics, displaying high binding affinities to the GluR3 binding pocket. CONCLUSIONS: These findings suggest that targeting GluR3 could hold promise for the development of therapies for depression and AD. Further validation through in vitro, in vivo, and clinical studies is necessary to explore the potential of these compounds as lead candidates for potent and selective GluR3 inhibitors. The shared molecular mechanisms between depression and AD provide an opportunity for novel treatment approaches that address both conditions simultaneously.

PVT1 lncRNA in lung cancer: A key player in tumorigenesis and therapeutic opportunities.

The lncRNA PVT1 has emerged as a pivotal component in the intricate landscape of cancer pathogenesis, particularly in lung cancer. PVT1, situated in the 8q24 chromosomal region, has garnered attention for its aberrant expression patterns in lung cancer, correlating with tumor progression, metastasis, and poor prognosis. Numerous studies have unveiled the diverse mechanisms PVT1 contributes to lung cancer pathogenesis. It modulates critical pathways, such as cell proliferation, apoptosis evasion, angiogenesis, and epithelial-mesenchymal transition. PVT1's interactions with other molecules, including microRNAs and proteins, amplify its oncogenic influence. Recent advancements in genomic and epigenetic analyses have also illuminated the intricate regulatory networks that govern PVT1 expression. Understanding PVT1's complex involvement in lung cancer holds substantial clinical implications. Targeting PVT1 presents a promising avenue for developing novel diagnostic biomarkers and therapeutic interventions. This abstract encapsulates the expanding knowledge regarding the oncogenic role of PVT1 in lung cancer, underscoring the significance of further research to unravel its complete mechanistic landscape and exploit its potential for improved patient outcomes.

Targeting Wnt/ß-Catenin Pathway by Flavonoids: Implication for Cancer Therapeutics.

The Wnt pathway has been recognized for its crucial role in human development and homeostasis, but its dysregulation has also been linked to several disorders, including cancer. Wnt signaling is crucial for the development and metastasis of several kinds of cancer. Moreover, members of the Wnt pathway have been proven to be effective biomarkers and promising cancer therapeutic targets. Abnormal stimulation of the Wnt signaling pathway has been linked to the initiation and advancement of cancer in both clinical research and in vitro investigations. A reduction in cancer incidence rate and an improvement in survival may result from targeting the Wnt/ß-catenin pathway. As a result, blocking this pathway has been the focus of cancer research, and several candidates that can be targeted are currently being developed. Flavonoids derived from plants exhibit growth inhibitory, apoptotic, anti-angiogenic, and anti-migratory effects against various malignancies. Moreover, flavonoids influence different signaling pathways, including Wnt, to exert their anticancer effects. In this review, we comprehensively evaluate the influence of flavonoids on cancer development and metastasis by focusing on the Wnt/ß-catenin signaling pathway, and we provide evidence of their impact on a number of molecular targets. Overall, this review will enhance our understanding of these natural products as Wnt pathway modulators.

Current Insights into Diagnosis, Prevention Strategies, Treatment, Therapeutic Targets, and Challenges of Monkeypox (Mpox) Infections in Human Populations.

In the wake of the emergence and worldwide respread of a viral infection called Monkeypox (Mpox), there is a serious threat to the health and safety of the global population. This viral infection was endemic to the western and central parts of Africa, but has recently spread out of this endemic area to various countries, including the United Kingdom (UK), Portugal, Spain, the United States of America (USA), Canada, Sweden, Belgium, Italy, Australia, Germany, France, the Netherlands, Israel, and Mexico. This is a timely review focusing on recent findings and developments in the epidemiology, clinical features, therapeutic targets, diagnosis, prevention mechanisms, research challenges and possible treatment for Mpox. To date (29 November 2022), there have been around 81,225 reported cases of Mpox. In most cases, this illness is mild; however, there is a fatality rate ranging from 1 to 10%, which might be increased due to associated complications and/or secondary infections. There is a real challenge in the diagnosis of Mpox, since its symptoms are very similar to those of other infections, including smallpox and chickenpox. Generally, to prevent/limit the risk and transmission of Mpox, the detection and isolation of infected individuals, as well as hand hygiene and cleanliness, are essential and effective approaches to control/combat this viral infection. Nevertheless, updated information about Mpox from different angles is lacking. Thus, this review provides updated and comprehensive information about the Mpox illness, which should highlight the global burden, pathogenicity, symptoms, diagnosis, prevention measures and possible treatment of this emerging disease.

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.

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.

Assessment of IL-12, mRNA expression, vitamin-D level, and their correlation among the Mycobacterium tuberculosis cases.

BACKGROUND: Tuberculosis (TB) presents serious health related complications caused by the Mycobacterium tuberculosis pathogen. Interleukin 12 (IL-12), plays a central role in T helper 1 (Th1) cells development that are implicated in chronic inflammatory pathogenesis as well as level of 1,25-dihydroxyvitamin D3 can impact on IL-12 mRNA expression at the transcriptional level. METHODS: The present study included clinically confirmed 100 Mycobacterium tuberculosis cases (TB) for assessment of IL-12 mRNA expression and vitamin-D level as well as equal number of healthy controls were also included. RESULTS: In TB cases, overall 13.01-fold higher IL-12 mRNA expression and 30.69 ng/ml vitamin-D level were observed. It was observed that higher expression of IL-12 mRNA expression was linked with TB cases had fever (p < 0.0001), night sweat (p = 0.003), sputum with blood (p = 0.03) as well as decreased vitamin-D level was linked with weight loss (p = 0.01), fever (p < 0.0001), night sweat (p = 0.008), sputum with blood (p = 0.005). TB cases with smoking (p < 0.0001) and alcoholism (p = 0.01, p = 0.0001) had significantly higher IL-12 mRNA expression and lower vitamin-D levels compared to its counterpart. It was observed that TB cases with vitamin-D deficiency, insufficiency, sufficiency had 19.51-fold, 14.64-fold, and 10.54-fold IL-12 mRNA expression respectively (deficiency vs insufficiency; p = 0.0003, deficiency vs sufficiency; p < 0.0001). A negative correlation was observed between IL-12 mRNA expression and vitamin-D level among the TB cases (r = -0.68, p < 0.0001). CONCLUSIONS: Higher IL-12 mRNA expression and lower vitamin-D expression among the TB cases may be responsible for the severity and pathogenesis of TB and alterations in IL-12 mRNA expression and vitamin-D may be influenced by the smoking and alcoholism habit of TB cases.

Detecting Preanalytical Errors Using Quality Indicators in a Hematology Laboratory.

BACKGROUND AND OBJECTIVES: Monitoring laboratory performance continuously is crucial for recognizing errors and fostering further improvements in laboratory medicine. This study aimed to review the quality indicators (QIs) and describe the laboratory errors in the preanalytical phase of hematology testing in a clinical laboratory. METHODS: All samples received in the Hematology Laboratory of the Maternity and Pediatric Hospital in Hail for 3 years were retrospectively reviewed and evaluated for preanalytical issues using a set of QIs. The rate of each QI was compared to the quality specifications cited in the literature. RESULTS: A total of 95002 blood samples were collected for analysis in the hematology laboratory from January 2017 through December 2019. Overall, 8852 (9.3%) were considered to show preanalytical errors. The most common were "clotted specimen" (3.6%) and "samples not received" (3.5%). Based on the quality specifications, the preanalytical QIs were classified generally as low and medium level of performance. In contrast, the sigma-based performance level indicates acceptable performance on all the key processes. Further analysis of the study showed a decreasing rate of preanalytical errors from 11.6% to 6.5%. CONCLUSIONS: Preanalytical errors remain a challenge to hematology laboratories. The errors in this case were predominantly related to specimen collection procedures that compromised the specimen quality. Quality indicators are a valuable instrument in the preanalytical phase that allows an opportunity to improve and explore clinical laboratory process performance and progress. Continual monitoring and management of QI data are critical to ensure ongoing satisfactory performance and to enhance the quality in the preanalytical phase.

Prospects of microbial-engineering for the production of graphene and its derivatives: Application to design nanosystms for cancer theranostics.

Cancer is known as one of the leading causes of morbidity and fatality, currently faced by our society. The prevalence of cancer related dieses is rapidly increasing around the world. To reduce the mortality rates, early diagnosis and subsequent treatment of cancer in timely manner is quite essential. Advancements have been made to achieve effective theranostics strategies to tackle cancerous dieses, yet very challenging to overcome this issue. Recently, advances made in the field of nanotechnology have shown tremendous potential for cancer theranostics. Different types of nanomaterials have been successfully employed to develop sophisticated diagnosis and therapy techniques. In this context, graphene and its derivatives e.g. graphene oxide (GO) and reduced graphene oxide (RGO) have been investigated as promising candidates to design graphene-based nanosystems for the diagnosis and therapeutic purpose. Further, to synthesize graphene and its derivatives different types of physicochemical methods are being adopted. However, each method has its own advantage and disadvantages. In this reference, among diverse biological methods, microbial technique can be one of the most promising and eco-friendly approach for the preparation of graphene and its derivatives, particularly GO and RGO. In this review, we summarize studies performed on the preparation of graphene and its derivatives following microbial routes meanwhile focus has been made on the preparation method and the possible mechanism involved therein. Thereafter, we have discussed applications of graphene and its derivatives to developed advanced nanosystem that can be imperative for the cancer theranostics. Results of recent studies exploring applications graphene based nanosystem for the preparation of different types of biosensors for early diagnosis; advanced therapeutic approaches by designing drug delivery nanosystems along with multifunctionality (e.g cancer imaging, drug delivery, photodynamic and photo thermal therapy) in cancer theranostics have been discussed. Particularly, emphasis has been given on the preparation techniques of graphene based nanosystems, being employed in designing of biosensing platforms, drug delivery and multifunctional nanosystems. Moreover, issues have been discussed on the preparation of graphene and its derivatives following microbial technique and the implementation of graphene based nanosystems in cancer theranostics.

Interaction of Ectodomain of Respiratory Syncytial Virus G Protein with TLR2/ TLR6 Heterodimer: An In vitro and In silico Approach to Decipher the Role of RSV G Protein in Pro-inflammatory Response against the Virus.

BACKGROUND: Human respiratory syncytial virus (RSV) has been shown to be linked with various forms of respiratory diseases, such as common cold and lower respiratory tract illnesses like pneumonia and bronchiolitis. TLRs play critical role in generating host immune response against RSV. TLRs are expressed not only on leukocytes but also on many other cell types and can recognize RSV. Previous studies have established that RSV can interact with TLR4 and initiate inflammatory cascade of cytokines. The data from a recent study indicated that TLR2/TLR6 is involved in RSV recognition and subsequent innate immune activation. However, the nature of binding and the envelope protein of RSV involved in this interaction with TLRs are not studied yet. OBJECTIVE: We hypothesized that RSV G protein can bind to TLRs and mediate the inflammatory immune response against the virus infection. Therefore, we investigated whether RSV G protein could activate innate immune response through TLR signaling. METHODS: Different TLR antagonists were used to assess the effect of the exposure of RSV and RSV G ectodomain in human primary small airway epithelial cells (HSAECs). Various inflammatory cytokines, chemokines and type I IFNs were measured by ELISA along with their mRNA expression by qPCR. In silico interaction of RSV G protein with TLR2/TLR6 was also analyzed. RESULTS: Results of ELISA and qPCR analysis have shown that TLR2/TLR6 signaling is activated in HSAECs upon RSV and RSV G protein exposure which initiates innate immune response against RSV. Moreover, RSV envelope protein G plays a crucial role in binding and activation of TLR2/TLR6 signaling. CONCLUSION: In summary, our study shows that TLR2/TLR6 play important role in the activation of innate immune response upon RSV recognition which could be helpful in promoting RSV clearance and preventing RSV-induced disease.

Antimicrobial Surveillance for Bacterial Uropathogens in Ha'il, Saudi Arabia: A Five-Year Multicenter Retrospective Study.

OBJECTIVE: Urinary tract infections (UTIs) are among the most common infections that require antibiotic intervention. Antibiotic surveillance programs are crucial to assess resistance patterns of microorganisms associated with UTIs and to tailor antibiotic therapy accordingly. Therefore, the aim of the current study is to investigate the prevalence of uropathogens and their antimicrobial susceptibility patterns in Ha'il region. METHODS: We conducted a retrospective study in two main hospitals in Ha'il over a 5-year period (January 2015 to December 2019). Laboratory reports and clinical data of patients with a positive urine culture (≥105 CFU/mL) were included in the study. RESULTS: A total of 428 patients were included in this study. The majority of positive cultures belonged to female patients (94.4%), adults (76.9%) and outpatients (74.3%). Generally, Escherichia coli was the most common pathogen (45%), followed by Klebsiella pneumoniae (17%) and Staphylococcus aureus (12%). Extended-spectrum ß-lactamase (ESBL) strains of E. coli (15.7%) and K. pneumoniae (19.7%) showed resistance to most tested antibiotics, while almost all Gram-negative uropathogens including ESBL strains presented low resistance to cefoxitin, imipenem and meropenem. Most strains of Staphylococcus aureus and Enterococcus faecalis were resistant to trimethoprim/sulfamethoxazole including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), whereas the activity of linezolid was monitored against almost all different strains of Gram-positive uropathogens. CONCLUSION: This surveillance study which was conducted over a 5-year period in the Ha'il region revealed that the most common UTI-associated pathogen was E. coli. Based on the current sensitivity profiles obtained from this surveillance, carbapenems and linezolid can be considered as a first therapeutic choice treating UTIs in Ha'il caused by Gram-negative and positive uropathogens, respectively. Frequent targeted surveillance programs for antibiotic-resistant pathogens and their susceptibility profiles are crucial to enable tailored empirical treatment for patients.

A descriptive analysis of PVL-positive multidrug-resistant Staphylococcus aureus in hospital-associated infections in Saudi Arabia.

Methicillin resistant Staphylococcus aureus infections impose a huge risk to public health in healthcare and community settings worldwide. Therefore, it is of interest to document data on the anti-biogramas and genotypes of isolates from Saudi Arabia. We assessed the antimicrobial susceptibility, determined spa (protein A gene) and analyzed multilocus MLST genotypes, and detected PVL gene in these isolates. We collected 28 clinical MRSA isolates, cultured and determined the minimum inhibitory concentrations of 17 antimicrobial agents using Vitek2 system (BioMerieux, USA) from 3 hospitals in Saudi Arabia during the year 2012. Polymorphic region of the spa and seven housekeeping genes were amplified and sequenced. BioNumerics v.5.1 (Applied Maths) was used for spa typing and MLST. Samples were screened for the presence of PVL and mecA genes using polymerase chain reaction (PCR). Analysis shows that all isolates were susceptible to chloramphenicol, rifampicin, nitrofurantoin, teicoplanin, daptomycin and vancomycin. The T4573/ST22 strains are found to be prevalent in the Saudi Arabia (N=6, 21%). We further noted that three isolates (t363/ST240 strain) were resistant to eight antimicrobial agents. Most of t4573/ST22 strains were PVL positive, resistant to ciprofloxacin and linked to HA-MRSA infections. We document data for the presence of emerging multi drug resistant S. aureus strains carrying the PVL gene circulating within hospitals. This highlights the urgent need for continuous active surveillance and implementation of prevention measures.

The common motives for appendectomy in Hail Region Saudi Arabia.

BACKGROUND: Appendectomy remains the most common emergency surgery. With the lack of literature from Saudi Arabia regarding the treatment for appendix disorders, this study aimed to identify the common motives for appendectomy in Northern Saudi Arabia. METHODOLOGY: Data referring to be resected appendix patients who were diagnosed during the period from January 2018 to December 2018 were included in the present study. The diagnosis of the resected appendix was confirmed by conventional histopathology. RESULTS: The most common cause for the appendectomy was acute appendicitis followed by gangrenous perforated appendicitis, chronic appendicitis, and lymphoid hyperplasia, representing 85/129(66%), 33/129(26%), 8/129(6%), and 3/129(2%), in this order. CONCLUSION: Appendectomy is a common procedure for the treatment of a large section of patients with appendicitis and appendicitis like clinical features. Acute appendicitis was the most motive for appendectomy followed by gangrenous perforated appendicitis in Northern Saudi Arabia.

Molecular docking based design of Inhibitors for viral Non-Nucleosidase as potential anti-retroviral agents.

Reverse Transcriptase (RT) inhibitors are highly promising agents for use as an effective anti-retroviral therapy (HAART) which is typically a combination of three or four antiretroviral drugs. We used direct drug design approach to discover new chemical entities for the target protein. The validated template of the protein targeting reverse transcriptase PDB ID 1JKH was extracted for three sites hydrophobic, steric, and electronic parameters explain the interactions at the active site by the inhibitors. We used the Zinc library of compounds to explore the possible leads for HAART through RT inhibition. We report 12 new chemical entities with possible activity against the targeted viral protein. These leads will provide new therapeutic means in antiretroviral therapy.