BACKGROUND: The assessment of the postmortem interval (PMI) represents one of the major challenges in forensic pathology. Because of their stability, microRNAs, or miRNAs, are anticipated to be helpful in forensic research.
OBJECTIVE: To see if estimation of PMI is possible using miRNA-21 and Hypoxia-inducible factor-1α (HIF-1α) expression levels in the heart samples from aluminum phosphide toxicity (Alpt).
METHODS: This was a cross sectional study on 60 post-mortem samples (heart tissues) collected at different intervals during forensic autopsies. The two groups were allocated equally according to the cause of death into Group I (non-toxicated deaths, n = 30): Deaths caused by other than toxicity, and Group II (toxicated deaths, n = 30): Deaths due to Alpt. MDA (Malondialdehyde) and GSH (Glutathione), were measured in heart tissues using ELIZA. MiRNA- 21and HIF-1α expression levels were measured in heart tissues at different PMI using RT-Q PCR. ROC curve for detection of toxicated deaths using miRNA-21 and HIF was carried out.
RESULTS: miRNA-21 and HIF-1α expression levels in Alp deaths were up regulated while GSH was downregulated with statistically significant difference. There was positive correlation between miRNA-21, HIF-1α and MDA with PMI while there was negative correlation between GSH and PMI in Alp deaths. In prediction of post mortem interval in Alp deaths miRNA-21 sensitivity and specificity were (75.9 %, 51.7 %, respectively) while HIF-1α sensitivity and specificity were 100 %.
CONCLUSIONS: PMI can be calculated using the degree to which particular miRNA-21 and HIF-1α are expressed in the heart tissue. The combination of miRNA-21 with HIF-1α in post mortem estimation is precious indicators.

GRAPHICAL ABSTRACT[Formula: see text].

UNASSIGNED: Diabetic kidney disease (DKD) is the most common and deranging microvascular complication of diabetes mellitus (DM). Podocytopathy is a key component of glomerular damage in DKD. Micro RNA-21 (miRNA-21) is an epigenetic regulator that plays a role in podocyte damage; however, the results of previous studies have not resolved the controversy about the role of miRNA-21 in the pathogenesis of DKD.
UNASSIGNED: The objective was to investigate the correlation between miRNA-21 levels and urinary nephrin, podocin, and urinary albumin-creatinine ratio (UACR) in patients with type 2 DM and albuminuria.
UNASSIGNED: This is a cross-sectional study.
UNASSIGNED: This study was carried out in internal medicine outpatient clinic of Cipto Mangunkusumo Hospital Jakarta, Indonesia.
UNASSIGNED: This study consisted of 42 adults with type 2 DM and albuminuria.
UNASSIGNED: The measurements include (1) Serum miRNA-21; (2) urinary podocin, nephrin, and albumin-creatinine ratio; and (3) serum miRNA-21 correlated to urinary podocin, nephrin, and albumin-creatinine ratio.
UNASSIGNED: The Spearman bivariate analysis to assess the correlation of miRNA-21 with nephrin, podocin, and UACR.
UNASSIGNED: The mean relative expression of miRNA-21 was 0.069 (0.024), the median for nephrin, podocin, and UACR was 35.5 (15.75-51.25) ng/mL, 0.516 (0.442-0.545) ng/mL, and 150 (94.56-335.75) ng/mL, respectively. A correlation between miRNA-21 and nephrin was observed (r = 0.598; P < .0001). There was a correlation between miRNA-21 and UACR (r = 0.604; P < .0001). No correlation was found between miRNA-21 and podocin.
UNASSIGNED: A lack of non-DM and non-albuminuric control population and small sample size. We could not exclude concurrent disease, and all other potential confounding variables, particularly those related to inflammation.
UNASSIGNED: The miRNA-21 can be considered an early biomarker for podocytopathy and albuminuria in DM, highlighting its potential for early diagnostic and therapeutic interventions. Further research is required to confirm these findings and explore their clinical applications, which could significantly alter management strategies for DKD.
UNASSIGNED: La maladie rénale diabétique (MRD) est la complication microvasculaire la plus fréquente et une des plus inquiétantes du diabète (DB). La podocytose est une composante clé des lésions glomérulaires en contexte de MRD. Le micro-ARN-21 (miARN-21) est un régulateur épigénétique impliqué dans les lésions podocytaires, mais les résultats des études précédentes n’ont pas résolu la controverse sur le rôle du miARN-21 dans la pathogenèse de la MRD.
UNASSIGNED: Étudier la corrélation entre le taux de miARN-21 et la néphrine, la podocine et le rapport albumine-créatinine (RAC) urinaires chez les patients atteints de diabète de type 2 et présentant une albuminurie.
UNASSIGNED: Étude transversale.
UNASSIGNED: La clinique ambulatoire de médecine interne de l’hôpital Cipto Mangunkusumo à Jakarta (Indonésie).
UNASSIGNED: 42 adultes diabétiques de type 2 présentant une albuminurie.
UNASSIGNED: (1) miARN-21 sérique; (2) podocine, néphrine et rapport albumine-créatinine urinaires; (3) le miARN-21 sérique corrélé à la podocine, à la néphrine et au rapport albumine-créatinine urinaires.
UNASSIGNED: L’analyse bivariée de Spearman a servi à évaluer la corrélation entre le taux de miARN-21 et la néphrine, la podocine et le rapport albumine-créatinine urinaires.
UNASSIGNED: L’expression relative moyenne du miARN-21 était de 0,069 ng/ml (0,024). La médiane s’établissait à 35,5 (15,75–51,25) ng/ml pour la néphrine, à 0,516 (0,442–0,545) ng/ml pour la podocine et à 150 (94,56–335,75) ng/ml pour le RAC. On a observé une corrélation entre le miARN-21 et la néphrine (r = 0,598; p = < 0,0001), de même qu’entre le miARN-21 et le RAC (r = 0,604; p = <0,0001). Aucune corrélation n’a été observée entre le miARN-21 et la podocine.
UNASSIGNED: L’étude ne comporte pas de population témoin (non-DB et sans albuminurie) et l’échantillon est de petite taille. Il n’a pas été possible d’exclure les maladies concomitantes, de même que toutes les autres variables confondantes potentielles, en particulier celles qui sont liées à l’inflammation.
UNASSIGNED: Chez les patients diabétiques, le miARN-21 peut être considéré comme un biomarqueur précoce de la podocytose et de l’albuminurie, ce qui met en évidence son potentiel à faire partie des interventions diagnostiques et thérapeutiques précoces. D’autres recherches sont nécessaires pour confirmer ces résultats et explorer leurs applications cliniques, ce qui pourrait modifier considérablement les stratégies de prise en charge de la maladie rénale diabétique.

UNASSIGNED: Taurine, an amino acid abundantly found in the brain and other tissues, has potential neuroprotective properties. Alzheimer\'s disease (AD) is a commonly occurring type of dementia, which becomes more prevalent as people age. This experiment aimed to assess the neuroprotective effects of taurine on SH-SY5Y cells by examining its impact on Dihydrotestosterone (DHT), Dihydroprogesterone (DHP), as well as the expression of miRNA-21 and miRNA-181.
UNASSIGNED: The effects of various taurine concentrations (0.25, and 0.75 mg/mL), and LPS (0.1, and 12 mg/mL) on the SH-SY5Y cell line were assessed using the MTT assay. The levels of DHT and DHP were quantified using an ELISA kit. Additionally, the expression levels of miRNA-181 and miRNA-21 genes were examined through Real-Time PCR analysis.
UNASSIGNED: The results of the MTT assay showed that treatment with taurine at concentrations of 0.25, and 0.75 mg/mL reduces the toxicity of LPS in SH-SY5Y cells. ELISA results indicated that taurine at a concentration of 0.25, and 0.75 mg/mL significantly elevated DHT and DHP hormones in the SH-SY5Y cell line compared to the untreated group (p < 0.01). The expression levels of IL-1β and IL-6 were decreased under the influence of LPS in SH-SY5Y cells after taurine treatment (p < 0.01). Gene expression analysis revealed that increasing taurine concentration resulted in heightened expression of miRNA-181 and miRNA-21, with the most significant increase observed at a concentration of 0.75 mg/mL (p < 0.001).
UNASSIGNED: Our study findings revealed that the expression of miRNA-181 and miRNA-21 can be enhanced by taurine. Consequently, exploring the targeting of taurine, miRNA-181, and miRNA-21 or considering hormone therapy may offer potential therapeutic approaches for treating AD or alleviating severe symptoms. Nonetheless, in order to fully comprehend the precise mechanisms involved, additional research is required.

miRNA-21 is regarded as both an abundant and highly conserved member of the microRNA (miRNA) family. It is expressed in virtually every cell and is responsible for critical regulatory actions that are important in health and disease. This microRNA has been shown to potentially have a role in the pathogenesis of several immune-related disorders, including autoimmune diseases, such as Multiple sclerosis and systemic lupus erythematosus, as two prominent examples of diseases that might be involved. In the current research, we looked at the role of miRNA-21, regarded as one of the most significant pathogenic miRNAs with a role in the development of autoimmune illness.

Herein, we constructed a fluorescence biosensor for the ultra-sensitive analysis of microRNAs (miRNAs) by combining DNA hairpins transition triggered strand displacement amplification (DHT-SDA) with primer exchange reaction (PER). Target miRNA initiated DHT-SDA to facilitate the generation of multiple single-stranded DNA (ssDNA) as PER primer, which was extended into a long ssDNA. The biosensor is successfully utilized in detecting miRNAs with high sensitivity (limit of detection for miRNA-21 was 58 fM) and a good linear relationship between 100 nM and 100 fM. By simply changing the DNA hairpin sequence, the constructed biosensor can be extended to analyze another miRNAs. Moreover, the biosensor has the feasibility of detecting miRNAs in real samples with satisfactory accuracy and reliability. Therefore, the fluorescent biosensor has great application potential in clinical diagnosis.

Oncogenic microRNA (miRNA), especially miRNA-21 upregulation in triple-negative breast cancer (TNBC), suggests a new class of therapeutic targets. In this study, we aimed to create GE11 peptide-conjugated small interfering RNA-loaded chitosan nanoparticles (GE11-siRNA-CSNPs) for the targeting of EGFR overexpressed TNBC and selectively inhibit miRNA-21 expression. A variety of in-silico and in vitro cellular and molecular studies were conducted to investigate the binding affinities of specific targets used as well as the anticancer efficacies and mechanisms of GE11-siRNA-CSNPs in TNBC cells. An in-silico assessment reveals a distinct binding affinity of miRNA-21 with siRNA as well as between the extracellular domain of EGFR and synthesized peptides. Notably, the in vitro results showed that GE11-siRNA-CSNPs were revealed to have better cytotoxicity against TNBC cells. It significantly inhibits miRNA-21 expression, cell migration, and colony formation. The results also indicated that GE11-siRNA-CSNPs impeded cell cycle progression. It induces cell death by reducing the expression of the antiapoptotic gene Bcl-2 and increasing the expression of the proapoptotic genes Bax, Caspase 3, and Caspase 9. Additionally, the docking analysis and immunoblot investigations verified that GE1-siRNA-CSNPs, which specifically target TNBC cells and suppress miRNA-21, can prevent the effects of miRNA-21 on the proliferation of TNBC cells via controlling EGFR and subsequently inhibiting the PI3K/AKT and ERK1/2 signaling axis. The GE11-siRNA-CSNPs design, which specifically targets TNBC cells, offers a novel approach for the treatment of breast cancer with improved effectiveness. This study suggests that GE11-siRNA-CSNPs could be a promising candidate for further assessment as an additional strategy in the treatment of TNBC.

UNASSIGNED: It is well-known that circulating microRNAs (miRNAs) play a relevant role in many kinds of diseases by regulating the expression of genes involved in various pathophysiologic processes, including erectile dysfunction (ED) and cardiovascular diseases (CVD).
UNASSIGNED: This study aimed to identify the miRNA-21 profile in the blood samples of patients with ED, CVD, and the combination of both pathologies to elucidate the potential function of miRNA-21.
UNASSIGNED: A total of 45 patients with CVD and/or who underwent the erectile function test were included and divided into the following categories: CVD with ED (cases, n = 29) and controls (n = 16) with either ED or CVD. Real-time polymerase chain reaction analysis verified the results. miRNA-21 expression was quantified, and informatics analysis was applied to predict the functions of this differentially expressed miRNA-21.
UNASSIGNED: A total of 64% of cases (63 ± 9 years, 66% with severe ED, 56% with CV ejection fraction) first presented ED as the sentinel clinical manifestation. Serum miRNA-21 levels in the control ED were significant, up to 10-fold higher than in the CVD controls and cases. A significant inverse (p = 0.0368, β = -2.046) correlation was found between erectile function and miRNA-21 levels.
UNASSIGNED: Our study provides comprehensive insights into the functional interaction between miRNA-21 and ED in CVD patients. Its relevance lies in the potential of miRNA as a biomarker to be applied in the cardiovascular predictive medicine field.

BACKGROUND: Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells.
RESULTS: The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process.
CONCLUSIONS: The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.

The abnormal expression levels of miRNAs have been proven to be highly related to the generation of various diseases and are also closely associated with the stages and types of disease development. The novel RNA aptamers-based homogenous fluorescent methods were simple, with low background signal and high signal-to-noise ratio, but lacked effective signal amplification technology to achieve sensitive detection of trace miRNA markers. There is an urgent need for combining effective nucleic acid amplification technology with RNA aptamer to achieve highly sensitive and accurate detection of miRNA. For this purpose, a new DNA multi-arm nanostructure-based dual rolling circle transcription machinery for the generation of lighting-up MG RNA aptamers is constructed for label-free and highly sensitive sensing of miRNA-21. In this system, the target miRNA-21 induces a structural transformation of the DNA multi-arm nanostructure probe to recycle miRNA-21 and trigger two independent rolling circle transcription reactions to generate two long RNAs, which can partially hybridize with each other to generate large amounts of complete MG RNA aptamers. These RNA aptamers can associate with organic MG dye to produce significantly enhanced fluorescence signals to accomplish ultrasensitive miRNA-21 detection down to 0.9 fM. In addition, this method exhibits high selectivity to distinguish miRNA-21 even with single nucleotide mismatch, and also has potential application capability to monitor different expression levels of miRNA-21 from different cancer cells. The effective collaboration between MG RNA aptamer and rolling circle transcription reaction makes this fluorescent method show the significant advantages of low background signal, high signal-to-noise ratio and high detection sensitivity. It has great potential to be a promising means to achieve label-free and highly sensitive monitoring of other trace biological markers via a simple change of target sequence.