Evidence linking COVID-19 and the health/well-being of children and adolescents: an umbrella review.

BACKGROUND: Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus. METHODS: In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures. RESULTS: We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression. CONCLUSIONS: The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.

The common diabetes drug metformin can diminish the action of citral against Rhabdomyosarcoma cells in vitro.

Rhabdomyosarcoma (RMS) is a rare type of soft tissue sarcoma most commonly found in pediatric patients. Despite progress, new and improved drug regimens are needed to increase survival rates. Citral, a natural product plant oil can induce cell death in cancer cells. Another compound, metformin, isolated originally from French lilac and used by diabetics, has been shown to reduce the incidence of cancer in these patients. Application of citral to RMS cells showed increase in cell death, and RD and RH30 cells showed half maximal inhibitory concentration (IC50 ) values as low as 36.28 µM and 62.37 µM, respectively. It was also shown that the citral initiated cell apoptosis through an increase in reactive oxygen species (ROS) and free calcium. In comparison, metformin only showed moderate cell death in RMS cell lines at a very high concentration (1,000 µM). Combinatorial experiments, however, indicated that citral and metformin worked antagonistically when used together. In particular, the ability of metformin to quench the ROS induced by citral could lead to the suppression of activity. These results clearly indicate that while clinical use of citral is a promising anti-tumor therapy, caution should be exercised in patients using metformin for diabetes.

A fast response fluorescence probe specific for hypochlorous acid detection and its applications in bioimaging.

Quantitative detection and visualization of hypochlorous acid (HOCl) in biological samples has emerged as a hot topic in biochemical research because of the important role of this biomolecule in live organisms. In this contribution, a novel 1,8-naphthalimide-based fluorescence probe, DNPH-NA, was designed and synthesized for HOCl detection in aqueous solutions and in biological systems. In the presence of HOCl, significant changes in absorption and fluorescence spectra were observed, which allow for the quantitative detection of HOCl in PBS buffer. The detection limit for HOCl was determined to be 50 nM. In the presence of HOCl, the fluorescence response of DNPH-NA was found to be completed within 2 seconds. The desirable features of DNPH-NA for the detection of HOCl in aqueous solutions, such as its high sensitivity and selectivity, reliability at physiological pH, rapid fluorescence response, and biocompatibility enabled its application in the detection of HOCl in biological samples. Imaging of exogenous HOCl in live HeLa cells and endogenous HOCl generation in live J774A.1 macrophage cells and zebrafish was then successfully performed using DNPH-NA as a fluorescence probe.

Quantitative Monitoring and Visualization of Hydrogen Sulfide In†Vivo Using a Luminescent Probe Based on a Ruthenium(II) Complex.

Development of novel bioanalytical methods for monitoring of H2 S is key toward understanding the physiological and pathological functions of this gasotransmitter in live organisms. A ruthenium(II)-complex-based luminescence probe, Ru-MDB (MDB: 4'-methyl-[2,2'-bipyridine]-4-yl)methyl 2-((2,4-dinitrophenyl)thio)benzoate), was developed by introducing a new H2 S responsive masking moiety to a red-emitting RuII luminophore. Cleavage of this masking group by a H2 S-triggered reaction leads to a luminescence "off-on" response. The long-lived emissions of Ru-MDB and its reaction product with H2 S allowed quantitative detection of H2 S in autofluorescence-rich human sera and adult zebrafish organs using the time-gated luminescence mode. Ru-MDB exhibits red emission, a large Stokes shift, high specificity and sensitivity for H2 S detection, and low cytotoxicity, which enables imaging and flow cytometry analysis of lysosomal H2 S generation in live inflamed cells under drug stimulation. Monitoring of H2 S in live Daphnia magna, zebrafish embryos, adult zebrafish, and mice, was conducted by in vivo imaging using Ru-MDB as a probe.

A Transcriptional Analysis Showing the Effects of GH12 Combined with Fluoride for Suppressing the Acidogenicity of Streptococcus mutans Biofilms.

The acidogenicity of Streptococcus mutans is important for caries development. The antimicrobial peptide GH12 can affect the integrity of cellular membranes and the virulence factors of S. mutans. Combining GH12 and NaF (GF) efficiently controlled the development of caries, but its mechanisms remained unrevealed. This research intended to verify the effects of GF on the acidogenicity of S. mutans biofilms and to reveal the mechanisms. Lactic acid production assays and pH monitoring assays were conducted to investigate the regulatory effects of the GF treatment on the acidogenicity of S. mutans biofilms. RNA sequencing and bioinformatics analyses were conducted to screen the transcriptional profile affected by the GF treatment. The results demonstrated the GF group had significantly less lactic acid and maintained the broth's pH values above 5.0 for longer times. Thereafter, GO/KEGG enrichment analyses and RT-qPCR validation revealed that the GF treatment mainly restrained the expression of genes related to the carbohydrates' internalization and metabolism. Compared with NaF, the GF treatment further downregulated the carbohydrates transportation genes. Moreover, compared with GH12, the GF treatment affected the membrane's integrity more significantly. Generally, GF treatment could arrest the acidogenicity of S. mutans biofilms, mainly through suppressing carbohydrates transportation and inhibiting overall metabolism.

Clinical performance of zirconium implants compared to titanium implants: a systematic review and meta-analysis of randomized controlled trials.

Purpose: To quantitatively assess and compare the clinical outcomes, including survival rate, success rate, and peri-implant indices of titanium and zirconium implants in randomized controlled trials. Methods: The electronic databases searched included the Cochrane Central Register of Controlled Trials (CENTRAL), Medline via Ovid, EMBASE, and Web of Science. Randomized controlled trials (RCTs) that reported the effects of zirconium implants on primary outcomes, such as survival rate, success rate, marginal bone loss (MBL), and probing pocket depth (PPD), compared to titanium implants were included in this review. Two reviewers independently screened and selected the records, assessed their quality, and extracted the data from the included studies. Results: A total of four studies from six publications reviewed were included. Two of the comparative studies were assessed at minimal risk of bias. Zirconium implants may have a lower survival rate (risk ratio (RR) = 0.91, CI [0.82-1.02], P = 0.100, I 2 = 0%) and a significantly lower success rate than titanium implants (RR = 0.87, CI [0.78-0.98], P = 0.030, I 2 = 0%). In addition, there was no difference between the titanium and zirconium implants in terms of MBL, PPD, bleeding on probing (BOP), plaque index (PI), and pink esthetic score (PES) (for MBL, MD = 0.25, CI [0.02-0.49], P = 0.033, I 2 = 0%; for PPD, MD = -0.07, CI [-0.19-0.05], P = 0.250, I 2 = 31%). Conclusion: Zirconium implants may have higher failure rates due to their mechanical weakness. Zirconium implants should be strictly assessed before they enter the market. Further studies are required to confirm these findings.

Exploitation of High Tumour GSH Levels for Targeted siRNA Delivery in Rhabdomyosarcoma Cells.

Metastatic alveolar rhabdomyosarcoma (aRMS) is an aggressive paediatric cancer with a poor prognosis. Downregulation of critical tumour genes using targeted siRNA remains an obstacle, but association with nanoparticles could help to deliver, protect, target, and enhance penetration. siRNA towards two genes was investigated: (i) Human αB-crystallin (CRYAB) and Heat Shock Protein Family B (Small) Member 2 (HSPB2), and (ii) Keratin 17 (KRT17). A mesoporous silica based nanosystem was linked to siRNA via disulfide bonds and loaded with IR820 dye. Transfection efficiency and signalling was evaluated, and the metabolic effects and cell proliferation were monitored in 2D culture and 3D spheroid models. The bound siRNA was protected from degradation with RNase I for at least 24 h. The delivered siRNA showed significant suppression of viability; 53.21 ± 23.40% for CRYAB and HSPB2 siRNA, and 88.06 ± 17.28% for KRT17 siRNA. After 72 h this increased to >50% cell apoptosis and necrosis. Intracellular total glutathione (GSH) levels were also compared with fibroblasts, and the RMS cell lines showed a several-fold increase. IR820 cellular uptake rate and penetration depth was significantly improved by nanoparticle delivery. Targetted siRNA delivery may pave the way for less invasive and more effective treatments of aRMS.

Isolation of NELL 1 Aptamers for Rhabdomyosarcoma Targeting.

NELL1 (Neural epidermal growth factor-like (EGFL)-like protein) is an important biomarker associated with tissue and bone development and regeneration. NELL1 upregulation has been linked with metastasis and negative prognosis in rhabdomyosarcoma (RMS). Furthermore, multiple recent studies have also shown the importance of NELL1 in inflammatory bowel disease and membranous nephropathy, amongst other diseases. In this study, several anti-NELL1 DNA aptamers were selected from a randomized ssDNA pool using a fluorescence-guided method and evaluated for their binding affinity and selectivity. Several other methods such as a metabolic assay and confocal microscopy were also applied for the evaluation of the selected aptamers. The top three candidates were evaluated further, and AptNCan3 was shown to have a binding affinity up to 959.2 nM. Selectivity was examined in the RH30 RMS cells that overexpressed NELL1. Both AptNCan2 and AptNCan3 could significantly suppress metabolic activity in RMS cells. AptNCan3 was found to locate on the cell membrane and also on intracellular vesicles, which matched the location of NELL1 shown by antibodies in previous research. These results indicate that the selected anti-NELL1 aptamer showed strong and highly specific binding to NELL1 and therefore has potential to be used for in vitro or in vivo studies and treatments.

Nanoparticles as Vectors to Tackle Cancer.

The aim of this Special Issue, "Nanoparticles for cancer therapy", was to offer readers a comprehensive and up-to-date insight into the various applications of nanoparticles in cancer treatments [...].

Responsive nanosensor for ratiometric luminescence detection of hydrogen sulfide in inflammatory cancer cells.

Gasotransmitter hydrogen sulfide (H2S), produced enzymatically in body, has important functions in biological signaling and metabolic processes. An abnormal level of H2S expression is associated with different diseases, therefore, development of novel bioanalytical methods for rapid and effective detection of H2S in biological conditions is of great importance. In this work, we report the development of a new responsive nanosensor for ratiometric luminescence detection of H2S in aqueous solution and live cells. The nanosensor (Ru@FITC-MSN) was prepared by immobilizing a luminescent ruthenium(II) (Ru(II)) complex into a fluorescein isothiocyanate (FITC) conjugated water-dispersible mesoporous silica nanoparticle (MSN), showing dual emission bands at 520 nm (FITC) and 600 nm (Ru complex). The red luminescence of the formed Ru@FITC-MSN was quenched in the presence of Cu2+. The in-situ generated Ru-Cu@FITC-MSN responded to H2S rapidly and selectively, showing a linear ratiometric luminescence change in FITC and Ru(II) channels with the H2S concentration (0.5-4 µM). Limit of detection (LoD) and limit of quantification (LoQ) were determined to be 0.36 and 1.21 µM. Followed by investigation of cellular uptake processes, the utility of the nanosensor for ratiometric imaging of H2S in live cells and its capability to monitor H2S levels in inflammatory breast cancer cells were then demonstrated. This study provides a powerful approach for detection of highly reactive and unstable H2S biomolecules in live systems.

Nanoparticle Activation Methods in Cancer Treatment.

In this review, we intend to highlight the progress which has been made in recent years around different types of smart activation nanosystems for cancer treatment. Conventional treatment methods, such as chemotherapy or radiotherapy, suffer from a lack of specific targeting and consequent off-target effects. This has led to the development of smart nanosystems which can effect specific regional and temporal activation. In this review, we will discuss the different methodologies which have been designed to permit activation at the tumour site. These can be divided into mechanisms which take advantage of the differences between healthy cells and cancer cells to trigger activation, and those which activate by a mechanism extrinsic to the cell or tumour environment.

Recent progress in upconversion luminescence nanomaterials for biomedical applications.

Upconversion nanoparticles (UCNPs) are one kind of luminescence nanomaterials that convert low energy photons to high energy emissions. These nanomaterials have recently attracted enormous attention due to their unique photophysical properties, such as resistance to photobleaching and photoblinking, low background autofluorescence, and long luminescence lifetime. Owing to these unique advantages, UCNPs have been widely examined for biomedical applications, including biosensing, imaging, and theranostics. In this review, we have first summarized the mechanisms for three generally accepted upconversion luminescence processes, i.e., lanthanide (Ln) doped upconversion luminescence, dye-sensitized upconversion, and triplet-triplet annihilation upconversion, and then discussed recent advancements on the preparation, functionalization, and biomedical applications of each type of UCNPs. The review article finally concludes with our perspectives on UCNPs' emerging and potential biomedical applications in the near future.

Responsive Fluorescence Probe for Selective and Sensitive Detection of Hypochlorous Acid in Live Cells and Animals.

The development of effective bioanalytical methods for rapid, sensitive and specific detection of HOCl in vitro and in vivo plays a key role for better understanding the roles of this molecule in normal and diseased conditions, but remains challenging due to the highly reactive nature of HOCl and the complicated biological conditions. In this work, a new fluorescence probe, PQI, was developed for monitoring of the HOCl level in biological samples. PQI was easily synthesized by a one-step condensation reaction. Upon addition of HOCl, significant changes in the absorption spectra and the color of the solution were noticed, facilitating the "naked eye" detection of HOCl in PBS buffer. The fluorescence of PQI was found to be significantly increased within a few seconds, leading to "OFF-ON" fluorescence response towards HOCl. The sensing mechanism, oxidation of thioether by HOCl, was confirmed by HRMS titration analysis. PQI features a large Stokes shift, high sensitivity and selectivity, and rapid fluorescence response towards HOCl. Quantitative detection of HOCl in single live cells was demonstrated through fluorescence imaging and flow cytometry analysis. PQI was then successfully used in visualisation of HOCl in live zebrafish and nude mice.