MicroRNA-138 inhibits hypoxia-inducible factor 1α expression in breast cancer cells.

BACKGROUND: Hypoxia, a critical feature during cancer development, leads to the stabilization and activation of the hypoxia-inducible factor 1-alpha (HIF-1α) to drive the expression of many target genes which in turn can promote many aspects of breast cancer biology, mainly metastasis and resistance to therapy. MicroRNAs are known to modulate the expression of many genes involved in breast cancer tumorigenesis. In this study, we examined the regulatory effect of miRNAs on HIF1α expression. METHODS: MCF-7 and MDA-MB-231 were cultivated under normoxia or hypoxia conditions. TaqMan-Low Density Array (TLDA) was used to characterize the miRNA signatures. Wild-Type (WT) or mutated fragments of HIF-1α 3'UTR containing the miR-138 potential target site were cloned downstream of the Renilla luciferase gene in the psiCHECK-1 plasmid. Luciferase assays were then carried out. A lentiviral vector containing copGFP as a reporter gene was prepared and transduced into MCF-7 and MDA-MB-231 cells to assess the effect of identified deregulated miRNAs on HIF-1α expression. RESULTS: Under hypoxic conditions, MCF-7 cells showed deregulated expression for 12 miRNAs. In the case of MDA-MB-231 cells, 16 miRNAs were deregulated in response to hypoxia. Interestingly, miR-138 that was downregulated in both MCF-7 and MDA-MB-231 cells cultivated under hypoxic conditions appeared to have a binding site in 3'UTR of HIF-1α. Moreover, our results indicated that miR-138 could down regulate HIF-1α expression, upon binding directly to its 3'UTR. CONCLUSIONS: Interestingly, our data highlights miR-138 as a potential therapeutic target to reduce HIF-1α expression and subsequently restrain breast cancer invasion and metastasis.

Neuroimaging findings in children with COVID-19 infection: a systematic review and meta-analysis.

The COVID-19 pandemic has impacted individuals differently, and there's been a growing body of evidence pointing to neurological complications caused by the virus. However, our understanding of the range of neurological issues linked to SARS-CoV-2 infection in children is limited. This systematic review and meta-analysis aimed to assess the abnormal neuroimaging findings in pediatric COVID-19 patients, shedding light on this crucial aspect of the disease's impact on children. We conducted an extensive search in the PubMed, Medline, and ScienceDirect databases for observational studies reporting neuroimaging findings of the brain and spinal cord in children with COVID-19 between December 1, 2019, and October 30, 2021. Grey literature sources, including medRxiv and Google Scholar, were also explored. Pooled proportions of abnormal neuroimaging findings, categorized into neurovascular findings, ADEM-like lesions, encephalitic pattern, myelitis, transient splenial lesions, and other anomalies, were calculated using a random-effects model. Between-study heterogeneity was assessed using the χ2 statistic for pooled proportions and the inconsistency index I2. The Quality of the studies was evaluated using the NIH Quality Assessment Tool and the adapted Newcastle-Ottawa Scale. Our search yielded 9,605 articles, with 96 studies (involving 327 pediatric patients) included in the qualitative analysis. Of these, five reports (encompassing 111 patients) underwent quantitative analysis. The pooled proportion of pediatric COVID-19 patients with neurological symptoms and exhibiting abnormal neuroimaging findings was 43.74%. These findings were further categorized into neurovascular findings (8.22%), ADEM-like lesions (7.69%), encephalitic pattern (13.95%), myelitis (4.60%), transient splenial lesions (16.26%), and other abnormalities (12.03%). Insignificant between-study heterogeneity was observed in all categories, and our analysis did not reveal significant publication bias. In conclusion, a substantial proportion of pediatric COVID-19 patients with neurological symptoms have abnormal neuroimaging findings, underscoring the need for vigilant monitoring of neurological complications in this vulnerable population. Standardized reporting and long-term follow-up studies are essential to fully understand the implications of these findings. Collaborative research efforts will deepen our understanding of COVID-19's neurological dimensions in children and enhance clinical care for this population.

Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution.

Propranolol is the first-line drug for managing migraine attacks. D-limonene is a citrus oil known for its neuroprotective mechanism. Thus, the current work aims to design a thermo-responsive intranasal limonene-based microemulsion mucoadhesive nanogel to improve propranolol efficacy. Microemulsion was fabricated using limonene and Gelucire® as the oily phase, Labrasol®, Labrafil®, and deionized water as the aqueous phase, and was characterized regarding its physicochemical features. The microemulsion was loaded in thermo-responsive nanogel and evaluated regarding its physical and chemical properties, in vitro release, and ex vivo permeability through sheep nasal tissues. Its safety profile was assessed via histopathological examination, and its capability to deliver propranolol effectively to rats' brains was examined using brain biodistribution analysis. Limonene-based microemulsion was of 133.7 ± 0.513 nm diametric size with unimodal size distribution and spheroidal shape. The nanogel showed ideal characteristics with good mucoadhesive properties and in vitro controlled release with 1.43-fold enhancement in ex vivo nasal permeability compared with the control gel. Furthermore, it displayed a safe profile as elucidated by the nasal histopathological features. The nanogel was able to improve propranolol brain availability with Cmax 970.3 ± 43.94 ng/g significantly higher than the control group (277.7 ± 29.71 ng/g) and with 382.4 % relative central availability, which confirms its potential for migraine management.

COVID-19 Vaccination Acceptability: A Cross-Sectional Study Among Lebanese Residents.

OBJECTIVE: Concerns about the side effects of available coronavirus disease (COVID-19) vaccines have posed a significant barrier to vaccination in several countries. Accordingly, the current study aimed to assess the acceptability of COVID-19 vaccination and its predictors among the Lebanese population. METHODS: A cross-sectional study was conducted in February 2021 among Lebanese adults from the 5 main Lebanese districts. The questionnaire included demographic data, questions about COVID-19 experience, COVID-19 anxiety syndrome scale, and attitudes regarding the COVID-19 vaccine. Data were analyzed on SPSS, version 23. Statistical significance was considered at a P value ≤ 0.05 with a 95% CI. RESULTS: Of 811 participants, 45.4% (95% CI: 41.9-48.9) accepted taking the COVID-19 vaccine. Choices were negatively affected by concerns about the side effects of the vaccine and positively affected by anxiety and seeking COVID-19 news very closely. Moreover, if the COVID-19 vaccination was a requirement for traveling, participants would be more willing to get the vaccine. CONCLUSIONS: Since 54.7% of the studied Lebanese adults were either unwilling or undecided to get the vaccine and COVID-19 news was retrieved mainly from the Ministry of Public Health online site and the local news, the existing targeted campaign should be enforced toward encouraging vaccination to reach herd immunity against COVID-19 and revealing the safety of the vaccines.

The Therapeutic Potential of Mesenchymal Stromal Cells for Regenerative Medicine: Current Knowledge and Future Understandings.

In recent decades, research on the therapeutic potential of progenitor cells has advanced considerably. Among progenitor cells, mesenchymal stromal cells (MSCs) have attracted significant interest and have proven to be a promising tool for regenerative medicine. MSCs are isolated from various anatomical sites, including bone marrow, adipose tissue, and umbilical cord. Advances in separation, culture, and expansion techniques for MSCs have enabled their large-scale therapeutic application. This progress accompanied by the rapid improvement of transplantation practices has enhanced the utilization of MSCs in regenerative medicine. During tissue healing, MSCs may exhibit several therapeutic functions to support the repair and regeneration of injured tissue. The process underlying these effects likely involves the migration and homing of MSCs, as well as their immunotropic functions. The direct differentiation of MSCs as a cell replacement therapeutic mechanism is discussed. The fate and behavior of MSCs are further regulated by their microenvironment, which may consequently influence their repair potential. A paracrine pathway based on the release of different messengers, including regulatory factors, chemokines, cytokines, growth factors, and nucleic acids that can be secreted or packaged into extracellular vesicles, is also implicated in the therapeutic properties of MSCs. In this review, we will discuss relevant outcomes regarding the properties and roles of MSCs during tissue repair and regeneration. We will critically examine the influence of the local microenvironment, especially immunological and inflammatory signals, as well as the mechanisms underlying these therapeutic effects. Importantly, we will describe the interactions of local progenitor and immune cells with MSCs and their modulation during tissue injury. We will also highlight the crucial role of paracrine pathways, including the role of extracellular vesicles, in this healing process. Moreover, we will discuss the therapeutic potential of MSCs and MSC-derived extracellular vesicles in the treatment of COVID-19 (coronavirus disease 2019) patients. Overall, this review will provide a better understanding of MSC-based therapies as a novel immunoregenerative strategy.

Circulating miRNAs: Potential diagnostic role for coronavirus disease 2019 (COVID-19).

Nowadays, the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major global health problem. Intensive efforts are being employed to better understand this pathology and develop strategies enabling its early diagnosis and efficient treatment. In this study, we compared the signature of circulating miRNAs in plasma of COVID-19 patients versus healthy donors. MiRCURY LNA miRNA miRNome qPCR Panels were performed for miRNA signature characterization. Individual quantitative real-time PCR (qRT-PCR) was carried out to validate miRNome qPCR results. Receiver-operator characteristic (ROC) curve analysis was applied to assess the diagnostic accuracy of the most significantly deregulated miRNA(s) as potential diagnostic biomarker(s). Eight miRNAs were identified to be differentially expressed with miR-17-5p and miR-142-5p being down-regulated whilst miR-15a-5p, miR-19a-3p, miR-19b-3p, miR-23a-3p, miR-92a-3p and miR-320a being up-regulated in SARS-CoV-2-infected patients. ROC curve analyses revealed an AUC (Areas Under the ROC Curve) of 0.815 (P = 0.031), 0.875 (P = 0.012), and 0.850 (P = 0.025) for miR-19a-3p, miR-19b-3p, and miR-92a-3p, respectively. Combined ROC analyses using these 3 miRNAs showed a greater AUC of 0.917 (P = 0.0001) indicating a robust diagnostic value of these 3 miRNAs. These results suggest that plasma miR-19a-3p, miR-19b-3p, and miR-92a-3p expression levels could serve as potential diagnostic biomarker and/or a putative therapeutic target during SARS-CoV-2-infection.

Comparing the osteogenic potential of schneiderian membrane and dental pulp mesenchymal stem cells: an in vitro study.

Mesenchymal stem cells, being characterized by high self-renewal capacity and multi-lineage differentiation potential, are widely used in regenerative medicine especially for repair of bone defects in patients with poor bone regenerative capacity. In this study, we aimed to compare the osteogenic potential of human maxillary schneiderian sinus membrane (hMSSM)-derived stem cells versus permanent teeth dental pulp stem cells (DPSCs). Both cells types were cultivated in osteogenic and non-osteogenic inductive media. Alkaline phosphatase (ALP) activity assay and quantitative real-time PCR analysis were carried out to assess osteogenic differentiation. We showed that ALP activity and osteoblastic markers transcription levels were more striking in hMSSM-derived stem cells than DPSCs. Our results highlight hMSSM-derived stem cells as a recommended stem cell type for usage during bone tissue regenerative therapy.

Biomonitoring of Aluminum in Urine of Young Lebanese Children Living in Beirut.

BACKGROUND Aluminum (Al) is a ubiquitous, toxic metal to which infants and young toddlers are highly vulnerable. High Al exposure has been associated with various human pathologies. The aim of the present biomonitoring (BM) study was to provide a background for the levels of urinary aluminum (Al) in children ages 7 months to 4 years living in Beirut. MATERIAL AND METHODS We collected and analyzed 120 urine specimens using the Shimadzu Atomic Absorption Spectrophotometer-6300 system equipped with an electrothermal atomization, and using a GFA-EX7i graphite furnace. RESULTS The mean and standard deviation of Al level in urine revealed 8.978±12.275 µg/L, which is within the lower range of each of populations in Germany, Taiwan, and Poland. Vitamin intake, powder rice, and the use of Al utensils proved to be major determinants for Al level in urine (significant at 95%). CONCLUSIONS The Shimadzu Atomic Absorption Spectrophotometer-6300 system proved again to be an optimal and reliable instrument that can be used for the determination of Al level in urine, especially if using a GFA-EX7i pyrolytic graphite furnace. High levels of Al were found in the urine of Lebanese children. However, the frequent consumption of canned food did not prove to be a significant factor in determining the Al level in urine.

A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: possible role of miRNA-125a-5p and miRNA-181a-5p.

BACKGROUND: Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Triple negative breast cancer (TNBC), lacking the expression of estrogen, progesterone and HER2 receptors, has an aggressive clinical phenotype and is susceptible to chemotherapy but not to hormonal or targeted immunotherapy. In an attempt to identify potent and selective anti-TNBC agents, a set of thiosemicarbazone derivatives were screened for their cytotoxic activity against MDA-MB 231 breast cancer cell line. METHODS: MTT assay was used to examine cell viability. P53 phosphorylation status, poly (ADP-ribose) polymerase (PARP) cleavage as well as Bcl2 and Bax protein levels were assessed by Western blot. Quantitative Real Time-PCR was carried out to characterize miRNAs expression levels. RESULTS: Combining Cisplatin + thiosemicarbazone compound 4 showed potent anti-TNBC potential. Cisplatin + compound 4 significantly enhanced p53 phosphorylation, induced Bax amount, reduced Bcl2 protein levels, enhanced PARP cleavage and modulated miRNAs expression profile in TNBCs, with a particular overexpression of miR-125a-5p and miR-181a-5p. Intriguingly, miR-125a-5p and miR-181a-5p could significantly downregulate BCL2 expression by binding to their target sites in the 3'UTR. CONCLUSIONS: Collectively, our results demonstrate an anti-TNBC activity of Cisplatin + thiosemicarbazone compound 4 combination mediated via induction of apoptosis.

Circulating miR-29c, miR-30c, miR-193a-5p and miR-885-5p: Novel potential biomarkers for HTLV-1 infection diagnosis.

Human T-cell leukemia virus type 1 (HTLV-1) is an oncoretrovirus that infects 5-10 million people worldwide. Currently, different methods are used to test HTLV-1 infection. However, a biomarker that could enable an early and accurate diagnosis of HTLV-1 infection is still lacking. Here, we compared the serum miRNA expression profile in HTLV-1 infected patients versus healthy individuals to identify a potential biomarker for diagnosis of HTLV-1 infection.TaqMan miRNA microarray (TLDA) was carried out to compare the miRNA expression profile in infected versus healthy individuals. Quantitative real-time RT-PCR (qRT-PCR) was applied to validate TLDA results. Receiver-operator characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of the most highly and significantly identified deregulated miRNA(s) as potential biomarker(s). We identified deregulated expression for ten miRNAs with miR-127, miR-136, miR-142-3p, miR-221, and miR-423-5p being down-regulated whilst let-7b, miR-29c, miR-30c, miR-193a-5p, and miR-885-5p being up-regulated in infected individuals. ROC curve analyses showed an AUC (Areas Under the ROC Curve) of 0.875 (95% CI: 0.7819-0.9581; P = .0021), 0.861 (95% CI: 0.7596-0.9754; P = .003), 0.856 (95% CI: 0.689-0.895; P = .011), and 0.849 (95% CI: 0.678-0.855; P = .017) for miR-29c, miR-30c, miR-193a-5p, and miR-885-5p respectively. Combined ROC analyses using these 4 miRNAs showed a greater AUC of 0.907 (95% CI: 0.809-1; P = .000001) indicating a robust diagnostic value of these 4 miRNAs. Our findings highlight serum miR-29c, miR-30c, miR-193a-5p and miR-885-5p as novel potential biomarkers important for HTLV-1 diagnosis.