BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load.
METHODS: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels.
RESULTS: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients.
CONCLUSIONS: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

OBJECTIVE: Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases. However, their roles and molecular mechanisms in major depressive disorder (MDD) remain largely unknown. This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms.
METHODS: Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD. C57 mice were subjected to chronic unpredictable mild stress (CUMS) to establish a depression model. Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice. Behavioral tests including the sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were conducted to evaluate depressive-like behaviors.
RESULTS: The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice. Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor (BDNF) and NPTN-IT1-201. ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls. Histological analyses, including HE and Nissl staining, showed marked structural changes in brain tissues following CUMS treatment, which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition. Immunofluorescence imaging demonstrated significant differences in the levels of BAX, Bcl2, p65, Iba1 among different treatment groups. TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions. Western blotting showed the significant differences in BDNF, BAX, and Bcl2 protein levels among different treatment groups.
CONCLUSIONS: NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p, making it a potential therapeutic target for MDD.

The growing prevalence of NAFLD and its global health burden have provoked considerable research on possible diagnostic and therapeutic options for NAFLD. Although various pathophysiological mechanisms and genetic factors have been identified to be associated with NAFLD, its treatment remains challenging. In recent years, exosomes have attracted widespread attention for their role in metabolic dysfunctions and their efficacy as pathological biomarkers. Exosomes have also shown tremendous potential in treating a variety of disorders. With increasing evidence supporting the significant role of exosomes in NAFLD pathogenesis, their theragnostic potential has become a point of interest in NAFLD. Expectedly, exosome-based treatment strategies have shown promise in the prevention and amelioration of NAFLD in preclinical studies. However, there are still serious challenges in preparing, standardizing, and applying exosome-based therapies as a routine clinical option that should be overcome. Due to the great potential of this novel theragnostic agent in NAFLD, further investigations on their safety, clinical efficacy, and application standardization are highly recommended.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is among the most malignant cancers in the world and has a high mortality rate. MicroRNAs (miRNAs) have progressively gained attention due to their roles in the pathogenesis and maintenance of various kinds of cancers, including OSCC. In this research, we carried out a scoping review to analyze the role of miRNA and therapeutic response in OSCC and focus on target axes associated with miRNA that inhibit metastasis and cell proliferation in OSCC.
METHODS: This review adhered to a six-stage methodology framework and PRISMA guidelines. Three databases were systematically searched to find eligible articles until July 2024. Two reviewers conducted publication screening and data extraction independently. 54 articles meeting the predefined inclusion criteria were successfully identified. Quality assessment was done using the QUIN checklist specified for dental in vitro studies.
RESULTS: Studies with different designs reported 53 miRNAs that were experimentally validated to act as therapeutic targets in OSCC in vivo and in vitro studies. The study found that 25 miRNAs were up-regulated in OSCC patients and cell lines, while another 25 were down-regulated. Mir-186 was also found to be up- and down-regulated in two different investigations. The study highlights the potential of six microRNAs (miR-32-5p, miR-195-5p, miR-3529-3p, miR-191, miR-146b-5p, and miR-377-3p) as anti-proliferation, migration, and invasion therapeutics for OSCC treatment. Two miRNAs (miR-302b and miR-18a) are identified as anti-metastatic therapeutics, while four miRNAs (miR-617, miR-23a-3p, miR-105, miR-101) are anti-proliferation therapeutics.
CONCLUSIONS: The study recommends that restoring the expression of tumor suppressor miRNAs may be a suitable cancer therapy. Utilizing this technology does present certain difficulties, and resolving them will improve the methods for miRNA transfer to target cells. With more research and the resolution of associated issues, miRNA can be employed as an efficient therapeutic method for OSCC.

Introduction: Cigarette smoke (CS) exacerbates the severity of diseases not only in lungs, but also in systemic organs having no direct contact with smoke. In addition, smoking during pregnancy can have severe health consequences for both the mother and the fetus. Therefore, our aim was to evaluate effects of prenatal exposure to CS on acetaminophen (APAP)-induced acute liver injury (ALI) in offspring. Methods: Female C57BL/6 mice on day 6 of gestation were exposed to mainstream CS (MSCS) at 0, 150, 300, or 600 μg/L for 2 h a day, 5 days a week for 2 weeks using a nose-only exposure system. At four weeks old, male offspring mice were injected intraperitoneally with a single dose of APAP at 300 mg/kg body weight to induce ALI. Results: Maternal MSCS exposure significantly amplified pathological effects associated with ALI as evidenced by elevated serum alanine aminotransferase levels, increased hepatocellular apoptosis, higher oxidative stress, and increased inflammation. Interestingly, maternal MSCS exposure reduced microRNA (miR)-34a-5p expression in livers of offspring. Moreover, treatment with a miR-34a-5p mimic significantly mitigated the severity of APAP-induced hepatotoxicity. Overexpression of miR-34a-5p completely abrogated adverse effects of maternal MSCS exposure in offspring with ALI. Mechanistically, miR-34a-5p significantly decreased expression levels of hepatocyte nuclear factor 4 alpha, leading to down-regulated expression of cytochrome P450 (CYP)1A2 and CYP3A11. Discussion: Prenatal exposure to MSCS can alter the expression of miRNAs, even in the absence of additional MSCS exposure, potentially increasing susceptibility to APAP exposure in male offspring mice.

With the increasingly severe situation of obesity and population aging, there is growing concern about sarcopenia obesity (SO). SO refers to the coexistence of obesity and sarcopenia, which imposes a heavier burden on individuals and society compared to obesity or sarcopenia alone. Therefore, comprehending the pathogenesis of SO and implementing effective clinical interventions are vital for its prevention and treatment. This review uses a comprehensive literature search and analysis of PubMed, Web of Science, and CNKI databases, with search terms including \"Sarcopenic obesity\", \"exercise\", \"cytokines\", \"inflammation\", \"mitochondrial quality control\", and \"microRNA\", covering relevant studies published up to July 2024. The results indicate that the pathogenesis of SO is complex, involving mechanisms like age-related changes in body composition, hormonal alterations, inflammation, mitochondrial dysfunction, and genetic and epigenetic factors. Regarding exercise interventions for SO, aerobic exercise can reduce fat mass, resistance exercise can increase skeletal muscle mass and strength, and combined exercise can achieve both, making it the optimal intervention for SO. The potential mechanisms by which exercise may prevent and treat SO include regulating cytokine secretion, inhibiting inflammatory pathways, improving mitochondrial quality, and mediating microRNA expression. This review emphasizes the effectiveness of exercise interventions in mitigating sarcopenic obesity through comprehensive analysis of its multifactorial pathogenesis and the mechanistic insights into exercise\'s therapeutic effects. Understanding these mechanisms informs targeted therapeutic strategies aimed at alleviating the societal and individual burdens associated with SO.

Despite the efforts to identify fluid biomarkers to improve diagnosis of Frontotemporal dementia (FTD), only a few candidates have been described in recent years. In a previous study, we identified three circulating miRNAs (miR-92a-3p, miR-320a and miR-320b) differentially expressed in FTD patients with respect to healthy controls and/or Alzheimer\'s disease (AD) patients. Now, we investigated whether those changes could be due to miRNAs contained in neuron-derived extracellular vesicles (NDEVs). We also evaluated miRNAs content in total plasma EVs and in CSF samples. The analysis of plasma NDEVs carried out on 40 subjects including controls (n = 13), FTD (n = 13) and AD (n = 14) patients, showed that both miR-92a-3p and miR-320a levels were triplicated in the FTD group if compared with CT and AD patients. Increased levels of the same miRNAs were found also in CSF derived from FTD group compared to CTs. No differences were observed in expression levels of miR-320b among the three groups. Worthy of note, all miRNAs analysed were increased in an FTD cell model, MAPT IVS10 + 16 neurons. Our results suggest that miR-92a and miR-320a in NDEVs could be proposed as FTD biomarkers.

BACKGROUND: Accurate detection of kidney damage is key to preventing renal failure, and identifying biomarkers is essential for this purpose. We aimed to assess the accuracy of miRNAs as diagnostic tools for chronic kidney disease (CKD).
METHODS: We thoroughly searched five databases (MEDLINE, Web of Science, Embase, Scopus, and CENTRAL) and performed a meta-analysis using R software. We assessed the overall diagnostic potential using the pooled area under the curve (pAUC), sensitivity (SEN), and specificity (SPE) values and the risk of bias by using the QUADAS-2 tool. The study protocol was registered on PROSPERO (CRD42021282785).
RESULTS: We analyzed data from 8351 CKD patients, 2989 healthy individuals, and 4331 people with chronic diseases. Among the single miRNAs, the pooled SEN was 0.82, and the SPE was 0.81 for diabetic nephropathy (DN) vs. diabetes mellitus (DM). The SEN and SPE were 0.91 and 0.89 for DN and healthy controls, respectively. miR-192 was the most frequently reported miRNA in DN patients, with a pAUC of 0.91 and SEN and SPE of 0.89 and 0.89, respectively, compared to those in healthy controls. The panel of miRNAs outperformed the single miRNAs (pAUC of 0.86 vs. 0.79, p < 0.05). The SEN and SPE of the panel miRNAs were 0.89 and 0.73, respectively, for DN vs. DM. In the lupus nephritis (LN) vs. systemic lupus erythematosus (SLE) cohorts, the SEN and SPE were 0.84 and 0.81, respectively. Urinary miRNAs tended to be more effective than blood miRNAs (p = 0.06).
CONCLUSIONS: MiRNAs show promise as effective diagnostic markers for CKD. The detection of miRNAs in urine and the use of a panel of miRNAs allows more accurate diagnosis.

BACKGROUND: MicroRNAs regulate post-transcriptional gene expression. Their expression has been linked to many pregnancy complications, including preterm birth. Placental microRNA levels differ between preterm and term pregnancies. Not much is known about the targets that are affected by these differences in microRNA expression. We investigated associations between microRNA expression levels in the basal plate of the placenta and their targets and the onset of preterm birth.
METHODS: MiRNAomes of spontaneous preterm (n = 6) and term (n = 6) placentas were characterized using RNA sequencing. MicroRNA target and enrichment analyses were performed to explore potential gene targets and pathways. Selected findings were validated using qPCR (n = 41). MicroRNA mimic transfection and luciferase reporter assays were performed to test if certain microRNAs regulate their predicted target, SLIT2, the expression of which has been shown to associate with preterm birth.
RESULTS: We identified 39 differentially expressed microRNAs from the preterm placentas compared to term. Many downregulated microRNAs were from the placenta-specific C14MC microRNA cluster. Target gene and pathway analyses showed that microRNAs that associate with preterm birth target transcription related factors and genes linked with protein binding and invasive pathways. Eight of the identified microRNAs putatively target SLIT2, including miR-766-3p and miR-489-3p. Luciferase reporter assay suggested that these microRNAs regulate SLIT2 expression.
CONCLUSIONS: MicroRNA expression changes are associated with spontaneous preterm birth. A group of microRNAs targeting the same gene or genes belonging to the same pathway can have a significant effect on the critical processes maintaining pregnancy and placental functions.

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