A reliable and selective ratiometric sensing probe for fluorometric determination of P2O74- based on AIE of GSH@CuNCs-assisted by Al-N@CQDs.

In this study, a novel composite material was developed for the ratiometric detection of pyrophosphate anion (P2O74-). This composite consisted of Al and nitrogen co-doped carbon dots (Al-N@CQDs) and glutathione-capped copper nanoclusters (GSH@CuNCs). The Al-N@CQDs component, with its high reserved coordination capacity of Al3+, induced the non-luminescent behavior of GSH@CuNCs, resulting in an aggregation-induced emission (AIE) effect. The hybrid material (Al-N@CQDs/GSH@CuNCs) exhibited dual-emission signals at 620 nm and 450 nm after integrating the two independent materials utilizing the AIE effect and the fluorescence resonance energy transfer (FRET) approach. This approach represents the first utilization of this composite for ratiometric detection. Nevertheless, upon the addition of P2O74-, the AIE and FRET processes were hindered due to the higher coordination interaction of Al3+ towards P2O74- compared to the amino/carboxyl groups on Al-N@CQDs. This successful interference of the AIE and FRET processes allowed for the effective estimation of P2O74-. The response ratio (F450/F620) increased with increasing the concentration of P2O74- in the range of 0.035-160 µM, with an impressive detection limit of 0.012 µM. This innovative approach of utilizing hybrid CQDs/thiolate-capped nanoclusters as a ratiometric fluorescent sensor for analytical applications introduces new possibilities in the field. The as-fabricated system was successfully applied to detect P2O74- in different real samples such as water, serum, and urine samples with acceptable results.

From diagnosis to resistance: a symphony of miRNAs in pheochromocytoma progression and treatment response.

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.

Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction.

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.

Facile fabrication of boron and nitrogen co-doped carbon dots for "ON-OFF-ON" fluorescence sensing of Al3+ and F- ions in water samples.

Water contamination with harmful ions has grown to be a significant environmental issue on a global scale. Therefore, the fabrication of simple, cost-effective, and reliable sensors is essential for identifying these ions. Herein, co-doping of carbon dots with new caffeine and H3BO3-derived boron (B) and nitrogen (N) was performed (BN@CDs). The as-prepared BN@CDs probe was used for the tandem fluorescence sensing of Al3+ and F- based on "ON-OFF-ON" switches. The BN@CDs nanoswitch has a high quantum yield of 44.8% with λexc. and λem. of 360 nm and 440 nm, respectively. The probe exhibited good stability with different pH, ionic-strengths, and irradiation times. The fluorescence emission of BN@CDs was decreased as the Al3+ concentration was increased with a linear range of 0.03-90 µM and a limit of detection (S/N = 3) equal to 9.0 nM. Addition of F- restored the BN@CDs emission as F- ions form a strong and stable complex with Al3+ ions [Al(OH)3F]-. Therefore, the ratio response (F/F°) was raised by raising the F- ion concentration to the range of 0.18-80 µM with a detection limit (S/N = 3) of 50.0 nM. The BN@CDs sensor exhibits some advantages over other reported methods in terms of simplicity, high quantum yield, and low detection limit. Importantly, the sensor was successfully applied to determine Al3+ and F- in various ecological water specimens with accepted results.

miRNAs orchestration of gallbladder cancer - Particular emphasis on diagnosis, progression and drug resistance.

Gallbladder cancer (GBC) is characterized by a highly invasive nature and a poor prognosis, with adenocarcinoma being the main histological subtype. According to statistical data, patients diagnosed with advanced GBC have a survival rate of less than 5% for 5 years. Despite the novel therapeutic techniques, the unsatisfactory results could be related to the underlying biology of tumor cells and resistance to chemotherapy. Early diagnosis is more important than clinical therapy as it assists in determining the pathological stage of cancer and facilitates the selection of appropriate medication. Hence, it is very important to understand the precise pathogenesis of GBC and to discover potential novel biomarkers for early diagnosis of GBC. Non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been found to influence the transcriptional regulation of target genes associated with cancer, either directly or indirectly. microRNAs are a group of small, non-coding, single-stranded RNAs that are expressed endogenously. miRNAs play significant roles in various fundamental cellular processes. Therefore, miRNAs have the potential to serve as valuable biomarkers and therapeutic targets for GBC.

The potential role of miRNAs in the pathogenesis of testicular germ cell tumors - A Focus on signaling pathways interplay.

Testicular germ cell tumors (TGCTs) are the most common testicular neoplasms in adolescents and young males. Understanding the genetic basis of TGCTs represents a growing need to cope with the increased incidence of these neoplasms. Although the cure rates have been comparatively increased, investigation of mechanisms underlying the incidence, progression, metastasis, recurrence, and therapy resistance is still necessary. Early diagnosis and non-compulsory clinical therapeutic agents without long-term side effects are now required to reduce the cancer burden, especially in the younger age groups. MicroRNAs (miRNAs) control an extensive range of cellular functions and exhibit a pivotal action in the development and spreading of TGCTs. Because of their dysregulation and disruption in function, miRNAs have been linked to the malignant pathophysiology of TGCTs by influencing many cellular functions involved in the disease. These biological processes include increased invasive and proliferative perspective, cell cycle dysregulation, apoptosis disruption, stimulation of angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and resistance to certain treatments. Herein, we present an up-to-date review of the biogenesis of miRNAs, miRNA regulatory mechanisms, clinical challenges, and therapeutic interventions of TGCTs, and role of nanoparticles in the treatment of TGCTs.

miRNAs orchestration of testicular germ cell tumors - Particular emphasis on diagnosis, progression and drug resistance.

Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management.

miRNAs orchestration of cardiovascular diseases - Particular emphasis on diagnosis, and progression.

MicroRNAs (miRNAs; miRs) are small non-coding ribonucleic acids sequences vital in regulating gene expression. They are significant in many biological and pathological processes and are even detectable in various body fluids such as serum, plasma, and urine. Research has demonstrated that the irregularity of miRNA in multiplying cardiac cells is linked to developmental deformities in the heart's structure. It has also shown that miRNAs are crucial in diagnosing and progressing several cardiovascular diseases (CVDs). The review covers the function of miRNAs in the pathophysiology of CVD. Additionally, the review provides an overview of the potential role of miRNAs as disease-specific diagnostic and prognostic biomarkers for human CVD, as well as their biological implications in CVD.

The potential role of miRNAs in the pathogenesis of cardiovascular diseases - A focus on signaling pathways interplay.

For the past two decades since their discovery, scientists have linked microRNAs (miRNAs) to posttranscriptional regulation of gene expression in critical cardiac physiological and pathological processes. Multiple non-coding RNA species regulate cardiac muscle phenotypes to stabilize cardiac homeostasis. Different cardiac pathological conditions, including arrhythmia, myocardial infarction, and hypertrophy, are modulated by non-coding RNAs in response to stress or other pathological conditions. Besides, miRNAs are implicated in several modulatory signaling pathways of cardiovascular disorders including mitogen-activated protein kinase, nuclear factor kappa beta, protein kinase B (AKT), NOD-like receptor family pyrin domain-containing 3 (NLRP3), Jun N-terminal kinases (JNKs), Toll-like receptors (TLRs) and apoptotic protease-activating factor 1 (Apaf-1)/caspases. This review highlights the potential role of miRNAs as therapeutic targets and updates our understanding of their roles in the processes underlying pathogenic phenotypes of cardiac muscle.

Long non-coding RNAs and rheumatoid arthritis: Pathogenesis and clinical implications.

Long non-coding RNAs (lncRNAs) are a class of noncoding RNAs with a length larger than 200 nucleotides that participate in various diseases and biological processes as they can control gene expression by different mechanisms. Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder characterized by symmetrical destructive destruction of distal joints as well as extra-articular involvement. Different studies have documented and proven the abnormal expression of lncRNAs in RA patients. Various lncRNAs have proven potential as biomarkers and targets for diagnosing, prognosis and treating RA. This review will focus on RA pathogenesis, clinical implications, and related lncRNA expressions that help to identify new biomarkers and treatment targets.

miRNAs as potential game-changers in bone diseases: Future medicinal and clinical uses.

MicroRNAs (miRNAs), short, highly conserved non-coding RNA, influence gene expression by sequential mechanisms such as mRNA breakdown or translational repression. Many biological processes depend on these regulating substances, thus changes in their expression have an impact on the maintenance of cellular homeostasis and result in the emergence of a variety of diseases. Relevant studies have shown in recent years that miRNAs are involved in many stages of bone development and growth. Additionally, abnormal production of miRNA in bone tissues has been closely associated with the development of numerous bone disorders, such as osteonecrosis, bone cancer, and bone metastases. Many pathological processes, including bone loss, metastasis, the proliferation of osteosarcoma cells, and differentiation of osteoblasts and osteoclasts, are under the control of miRNAs. By bringing together the most up-to-date information on the clinical relevance of miRNAs in such diseases, this study hopes to further the study of the biological features of miRNAs in bone disorders and explore their potential as a therapeutic target.

miRNAs as potential game-changers in renal cell carcinoma: Future clinical and medicinal uses.

Renal cell carcinoma (RCC) has the highest mortality rate of all genitourinary cancers, and its prevalence has grown over time. While RCC can be surgically treated and recurrence is only probable in a tiny proportion of patients, early diagnosis is crucial. Mutations in a large number of oncogenes and tumor suppressor genes contribute to pathway dysregulation in RCC. MicroRNAs (miRNAs) have considerable promise as biomarkers for detecting cancer due to their special combination of properties. Several miRNAs have been proposed as a diagnostic or monitoring tool for RCC based on their presence in the blood or urine. Moreover, the expression profile of particular miRNAs has been associated with the response to chemotherapy, immunotherapy, or targeted therapeutic options like sunitinib. The goal of this review is to go over the development, spread, and evolution of RCC. Also, we emphasize the outcomes of studies that examined the use of miRNAs in RCC patients as biomarkers, therapeutic targets, or modulators of responsiveness to treatment modalities.

The role of miRNAs in liver diseases: Potential therapeutic and clinical applications.

MicroRNAs (miRNAs) are a class of short, non-coding RNAs that function post-transcriptionally to regulate gene expression by binding to particular mRNA targets and causing destruction of the mRNA or translational inhibition of the mRNA. The miRNAs control the range of liver activities, from the healthy to the unhealthy. Considering that miRNA dysregulation is linked to liver damage, fibrosis, and tumorigenesis, miRNAs are a promising therapeutic strategy for the evaluation and treatment of liver illnesses. Recent findings on the regulation and function of miRNAs in liver diseases are discussed, with an emphasis on miRNAs that are highly expressed or enriched in hepatocytes. Alcohol-related liver illness, acute liver toxicity, viral hepatitis, hepatocellular carcinoma, liver fibrosis, liver cirrhosis, and exosomes in chronic liver disease all emphasize the roles and target genes of these miRNAs. We briefly discuss the function of miRNAs in the etiology of liver diseases, namely in the transfer of information between hepatocytes and other cell types via extracellular vesicles. Here we offer some background on the use of miRNAs as biomarkers for the early prognosis, diagnosis, and assessment of liver diseases. The identification of biomarkers and therapeutic targets for liver disorders will be made possible by future research into miRNAs in the liver, which will also help us better understand the pathogeneses of liver diseases.

Double-signal quantification of amoxicillin based on interaction with 4-aminoantipyrine at copper and nitrogen co-doped carbon quantum dots as an artificial nanozyme.

An one-pot hydrothermal method was developed for synthesis of carbon quantum dots co-doped with copper and nitrogen (Cu, N@CQDs). The synthesized Cu, N@CQDs has unique advantages such as high fluorescence quantum yield (39.1%) and high catalytic activity. Oxidative coupling of amoxicillin (AMX) with 4-aminoantipyrine (4-NH2-APE) in the presence of H2O2 as an oxidant to produce pink quinoneimine chromogen was carried out with the aid of Cu, N@CQDs as a peroxidase-like catalyst. This system was used for the colorimetric and fluorometric assays of AMX with reliable results. Colorimetric method is based on the measurement of a pink-colored product at λmax = 505 nm while the fluorometric assay is based on the quenching of the fluorescence emission of Cu, N@CQDs at 440 nm after excitation at 370 nm. For the colorimetric method, the absorption intensity linearly increased over the concentration range 4.3-110.0 µM with LOD (S/N = 3) of 1.3 µM. For the fluorometric method, the emission intensity of Cu, N@CQDs linearly decreased upon addition of AMX in the concentration range 0.2-120.0 µM with a limit of detection (LOD, S/N = 3) of 0.06 µM. The proposed system was applied to the determination of AMX in different real samples such as pharmaceutical capsules, human serum, milk, and conduit water samples with recoveries in the range 95.8-104.1% and relative standard deviation (RSD %) less than 4.1%.

Fabrication of water compatible and biodegradable super-paramagnetic molecularly imprinted nanoparticles for selective separation of memantine from human serum prior to its quantification: An efficient and green pathway.

A novel green magnetic molecularly imprinted solid phase extraction (MMI-SPE) for separation of memantine (MEM) from complicated matrices was proposed. The nanomaterial was synthesized via crosslinking of chitosan (CHIT) with [3-(2, 3-epoxypropoxy)-propyl] trimethoxysilane (EPPTMS) in presence of MEM as a template. The nanocomposites, in all steps, were characterized by SEM, FTIR and PXRD techniques. The adsorbed drug was removed from magnetic molecular imprinted polymer (MMIP) cavity by ethanol: acetic acid (8:2, v/v) and then, coupled with sodium 1, 2-naphthoquinone-4-sulphonate (NQS) in iodine/alkaline medium to yield highly fluorescent product, after reduction with potassium borohydride (KBH4). Variables affecting extraction of MEM from imprinted sites and its fluorometric analysis were studied. The linearity was achieved over concentration range of 1.84-95.0 ng mL-1 with LOD of 0.6 ng mL-1. The method was successfully applied for determination of MEM in its pharmaceutical tablets and human serum with recoveries of 100.8 ±â€¯3.0, 97.6 ±â€¯2.9, respectively.

Determination of donepezil in spiked rabbit plasma by high-performance liquid chromatography with fluorescence detection.

The aim of this paper is to develop sensitive, accurate, reproducible and robust RP-HPLC with fluorescence detection for estimation of donepezil (DZ) in rabbit plasma using silodosin as the internal standard (IS). The prepared samples were quantified on reversed phase column Luna C18(2) (150 × 4.6 mm i.d., 5 µm particle size) operated at room temperature using the mobile phase consisting of methanol: 0.1% acetic acid (50 : 50, v/v) at a flow rate of 1 ml min-1. The method was fully validated according to bioanalytical validation guidelines of FDA in terms of system suitability, selectivity, sensitivity, precision and stability. It was found that the increase in peak areas followed the increase of DZ concentration in the range of 2.56-200.00 ng ml-1 with LOD of 0.85 ng ml-1. The method was successfully applied for the determination of DZ in rabbit plasma using manual shaking dispersive liquid-liquid microextraction.

University students' knowledge of corneal donation and willingness to donate corneas in the occupied Palestinian territory: a cross-sectional study.

BACKGROUND: Access to corneal transplantation is limited worldwide because of poor knowledge. Ethical, religious, and cultural barriers contribute to low rates of corneal donation. In the occupied Palestinian territory, limited information is available on factors affecting corneal donation. The aim of this study was to assess the knowledge and willingness towards corneal donation in Palestinian students. METHODS: This cross-sectional study included university students selected through convenience sampling in Nablus in the summer of 2016. The sample size was determined using the sample formulae and a 15% non-response rate. All students registered in obligatory courses were included in the study after verbal consent. Each participant was given a self-administered questionnaire consisting of 14 questions to assess knowledge, awareness, and willingness toward corneal donation. Frequencies were used for descriptive analysis, and associations were determined using multivariate analysis and χ2 test, with a p value of less than 0·05 considered significant. FINDINGS: Of the 634 students completing the questionnaire, 411 (65%) were women, 614 (97%) were Muslims, and 155 (25%) were health or medical students. 592 (93%) respondents were unaware of eye bank availability, and 407 (69%; p=0.002) of these respondents did not show willingness towards corneal donation. 431 (67%) respondents were aware of a lack in corneal donation, but 274 (64%; p=0·01) of these respondents did not show willingness towards corneal donation. 429 (68%) respondents were not willing to donate their corneas, the most common reasons being disapproval by family members and poor awareness. We found no association between sociodemographic factors and willingness was determined. INTERPRETATION: Palestinian students are aware of the lack of local cornea donation but are unwilling to donate their corneas. The study results are not representative of the entire population because of the homogeneous nature of the sample. Large efforts are needed locally to develop the eye bank infrastructure to increase knowledge and awareness relating to corneal donation. FUNDING: None.