Journal of Investigative Medicine

MicroRNA-7 (miR-7) is a small non-coding RNA, which plays critical roles in regulating gene expression of multiple key cellular processes. MiR-7 exhibits a tissue-specific pattern of expression, with abundant levels found in the brain, spleen, and pancreas. Although it is expressed at lower levels in other tissues, including the liver, miR-7 is involved in both the development of organs and biological functions of cells. In this review, we focus on the mechanisms by which miR-7 controls cell growth, proliferation, invasion, metastasis, metabolism, and inflammation. We also summarize the specific roles of miR-7 in liver diseases. MiR-7 is considered as a tumor suppressor miRNA in hepatocellular carcinoma and is involved in the pathogenesis of hepatic steatosis and hepatitis. Future studies to further define miR-7 functions and its mechanism in association with other types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting miR-7 for the treatment of liver diseases.

As of 2017, 1.8 million people living with HIV (PLWH) were adolescents between ages 10 and 19, accounting for 5% of all PLWH and 590,000 people between the ages 15 and 24 were newly infected with HIV. Between 2004 and 2011, AIDS-related deaths increased 50% among adolescents, and optimal adolescent adherence to antiretroviral treatment (ART) is estimated at only 62% of adolescents worldwide. While there have been great strides toward achieving the UNAIDS 90-90-90 goals, adolescents remain a group lacking appropriate resources and research to achieve these. This review analyzes current interventions aimed toward increasing adolescent ART adherence. Systematic searches of EMBASE, PubMed and PsycINFO were performed using the keywords ‘adolescent HIV medication adherence interventions’. The Gain Score effect size was calculated for studies reporting the Cohen's d and variance to include both prestudy and poststudy values. A random-effects model analyzed intervention significance. Authors were contacted to obtain additional data values and study clarification. Twelve studies met inclusion criteria for meta-analysis. There were no significant differences seen between control and intervention groups in medication adherence (z=−1.4714, p<0.1412), viral load (z=−0.1946, p<0.8547) or CD4+ lymphocyte count (z=0.2650, p<0.7910). There was no significant difference between studies in increasing medication adherence. Results indicate that interventions did not improve medication adherence in adolescents with HIV. However, the paucity of quantitative research available speaks to a need for more quantitative intervention studies and standardization of measures of intervention efficacy.

Epithelial ovarian cancer (EOC) is the most common and leading cause of death for gynecologic cancer in the western world. Current standard treatments with limited selection of chemotherapies cannot meet patients’ urgent needs. Immunotherapies have recently demonstrated clinical benefits in a variety of solid tumors and may offer a promising frontier for treating EOC. Dendritic cells (DCs) are key coordinators of the innate and adaptive immune system in induction of antitumor immunity. DC-based vaccinations showed clinical benefits and encouraging safety profiles in a few phase II clinical trials for patients with EOC and currently are in a phase III double-blind, randomized, placebo-controlled clinical trial. In this review, we have searched Pubmed and Clinicaltrials. gov databases for past and current phase II or phase III clinical trials with focus on EOC and DC vaccines. Outcomes and implications of the completed and ongoing trials are discussed.

Healthcare providers commonly experience symptoms of anxiety during public health crises and pandemics. The objective of the study was to identify the frequency of symptoms of generalized anxiety disorder (GAD) in general practitioners and to estimate the association with particular psychosocial and demographic factors. This is a cross-sectional study, where a total of 531 general practitioners completed an online form that contained sociodemographic variables, questions about fear and perceptions concerning medical work during the COVID-19 pandemic, 7-Item Generalized Anxiety Disorder Scale (GAD-7), questionnaire on psychosomatic problems and Fear of COVID-19 Scale. The presence of symptoms of GAD was defined by a GAD-7 score of 10 or more points. Voluntary and anonymous participation, acceptance of terms, and informed consent were requested. A p value of <0.05 was considered statistically significant. Symptoms of GAD were identified in 4 out of 10 Colombian general practitioners; the following psychosocial and demographic factors were associated with a greater presence of these symptoms: female gender, social discrimination, anguish, job disappointment, nightmares, stress and other symptoms of fear regarding the pandemic. Conversely, feeling protected by the state or employer, being satisfied with their job as a physician, and trusting government measures and information were associated with a lower presence of symptoms of GAD. These findings highlight the importance of timely psychotherapeutic and psychopharmacological interventions in these individuals. The authors suggest mental health providers should be deployed during times of crisis to decrease the risk of developing mental illness.

Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. We compared these values with healthy control subjects. The mean age was 63.3±11.2 years. Fifty percent of the patients were women. Thirteen patients (32.5%) died during this hospitalization. The mean maximum glucose level on the day of admission was 215.7±171.1 mg/dL. Compared with control subjects, there was a significant reduction in advanced glycation end product levels (p=0.0001) in the patients at all 3 time points. Circulating glycated hemoglobin levels were significantly higher in patients compared with control subjects. We also observed a moderate increase in glycated albumin levels on admission and at 24 hours when compared with the control samples. Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.

Early recognition of severe clinical outcomes in children with pneumonia-related bacteremia is vitally important because of the high mortality. This study aims to explore risk factors for severe clinical outcomes in children with pneumonia-related bacteremia and evaluate the value of time to first positive blood cultures (TTFP) in predicting prognosis. Children with pneumonia-related bacteremia in Children's Hospital of Chongqing Medical University were included (January 2013-May 2019), respectively. TTFP and clinical parameters were collected and analyzed. The area under the curve (AUC)-receiver operating characteristic was used to evaluate the discrimination ability of TTFP. Multivariate logistic regression tests were performed to evaluate the association between TTFP and severe clinical outcomes. A total of 242 children with pneumonia-related bacteremia were included. The least absolute shrinkage and selection operator (LASSO) regression analysis identified TTFP, serum albumin (ALB) and lactic dehydrogenase (LDH) as predictors of in-hospital mortality. Multivariate logistic regression analysis showed that shorter TTFP (OR 0.94; 95% CI 0.89 to 0.97; p<0.01), lower ALB level (OR 0.93; 95% CI 0.89 to 0.98; p<0.01) and higher LDH level (OR 1.001; 95% CI 1.000 to 1.001; p<0.01) were risk factors for in-hospital mortality in children with pneumonia-related bacteremia. AUC of TTFP for predicting in-hospital mortality was 0.748 (95% CI 0.668 to 0.829). Shorter TTFP (≤16 hours) was associated with in-hospital mortality and septic shock. TTFP plays an important role in predicting severe clinical outcomes in children with pneumonia-related bacteremia.

The present study aims to determine the potential prophylactic effect of clopidogrel for migraine with patent foramen ovale (PFO) in patients who are poor responders to two or more common preventive medications. Migraineurs underwent contrast-enhanced transcranial doppler examination to confirm the presence of PFO and determine the right-to-left shunt degree. Clopidogrel 75 mg/day was added to the existing prophylactic regimen for 3 months and 6 months. The presence of PFO was found in 56.8% (151/266) of all patients with migraine and 70.2% (59/84) of migraine with aura (MHA), and among MHA a large shunt was observed in 36 patients. Twenty-six patients with drug-refractory migraine took clopidogrel 75 mg/day for 3 months. Compared with those at baseline, headache frequencies and attack durations were significantly lower (6.17±3.93/month (M) vs 3.28±2.67/M, p=0.003; 13.62±13.98/hour (H) vs 7.36±7.33/H, p=0.0049, respectively); visual analog scale scores and migraine disability assessment scores were also obviously decreased (6.32±1.97 vs 4.71±1.20, p<0.001; 22.14±7.13 vs 16.00±5.92, p=0.001, respectively). These improvements were maintained for 6 months in 12 patients. We concluded that PFO was closely correlated with migraine, especially in MHA. Clopidogrel could act as an effective complementary prophylactic for migraine with PFO in patients with poor response to routine prophylactics.

Normothermia (36.5°C-37. 5°C) at the time of admission to the neonatal intensive care unit (NICU) in extremely low birthweight (ELBW) infants (birth weight <1000 g) is associated with decreased morbidity and mortality, decreased length of stay and hospital costs. We designed a thermoregulation bundle to decrease hypothermia (<36.5°C) in ELBW infants with a multidisciplinary perinatal quality improvement initiative that included the following key interventions: dedicated delivery room (DR)/operating room (OR) for all preterm deliveries of ≤32 weeks with DR/OR temperature set 24/7 at 74°F by the hospital engineering staff, use of exothermic mattress, preheated radiant warmer set at 100% for heat prior to delivery, servo-controlled mode after the neonate is placed on the warmer, and use of plastic wrap, head cap and warm towels. A total of 200 ELBW infants were admitted to our NICU between January 1, 2014 and December 31, 2019. Hypothermia (<36.5°C) occurred in 2.5% of infants, normothermia (36.5°C-37.5°C) in 91% of infants and transitional hyperthermia (>37.5°C) in 6.5% of ELBW infants. No case of moderate hypothermia (32°C-36°C) was seen in our infants. Our target rate of less than 10% hypothermia was reached in ELBW infants over the last 2 years with no cases of moderate hypothermia in 6 years. Eliminating hypothermia among ELBW remains a challenge and requires team effort and continuous quality improvement efforts.

Acute kidney injury (AKI) is a complication of COVID-19. However, the incidence of AKI in COVID-19 varies among studies. Thus, we aimed to evaluate the pooled incidence of AKI and its association with mortality in patients with COVID-19 using a meta-analysis. We search Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible publications reporting the clinical characteristics of patients with COVID-19 without language restriction. Incidence of AKI and mortality were reported. Meta-regression was used to describe the association between outcomes. From 26 studies (n=5497), the pooled incidence of AKI in patients with COVID-19 was 8.4% (95% CI 6.0% to 11.7%) with a pooled incidence of renal replacement therapy of 3.6% (95% CI 1.8% to 7.1%). The incidence of AKI was higher in critically ill patients (19.9%) compared with hospitalized patients (7.3%). The pooled estimated odds ratio for mortality from AKI was 13.33 (95% CI 4.05 to 43.91). No potential publication bias was detected. By using meta-regression analyses, the incidence of AKI was positively associated with mortality after adjusted for age and sex (Q=26.18; p=0.02). Moreover, age (p<0.01), diabetes (p=0.02), hypertension (p<0.01) and baseline serum creatinine levels (p=0.04) were positively associated with AKI incidence in adjusted models. In conclusion, AKI is present in 8.3% of overall patients with COVID-19 and in 19.9% of critically ill patients with COVID-19. Presence of AKI is associated with 13-fold increased risk of mortality. Age, diabetes, hypertension, and baseline serum creatinine levels are associated with increased AKI incidence.

Increased aortic stiffness may contribute to kidney damage by transferring excessive flow pulsatility to susceptible renal microvasculature, leading to constriction or vessel loss. We previously demonstrated that 5 weeks of dietary sodium restriction (DSR) reduces large-elastic artery stiffness as well as blood pressure in healthy middle-aged/older adults with moderately elevated systolic blood pressure (SBP) who are free from chronic kidney disease (CKD). We hypothesized that DSR in this cohort would also reduce urinary concentrations of renal tubular injury biomarkers, which predict incident CKD in the general population. We performed a post hoc analysis using stored 24 hours urine samples collected in 13 participants as part of a randomized, double-blind, crossover clinical trial of DSR (low sodium (LS) target: 50 mmol/day; normal sodium (NS) target: 150 mmol/day). Participants were 61±2 (mean±SEM) years (8 M/5 F) with a baseline blood pressure of 139±2/82±2 mm Hg and an estimated glomerular filtration rate of 79±3 mL/min/1.73 m². Twenty-four hour urinary sodium excretion was reduced from 149±7 to 66±8 mmol/day during week 5. Despite having preserved kidney function, participants had a 31% reduction in urinary neutrophil gelatinase-associated lipocalin concentrations with just 5 weeks of DSR (LS: 2.8±0.6 vs NS: 4.2±0.8 ng/mL, p<0.05). Results were similar when normalized to urinary creatinine (urinary creatinine did not change between conditions). Concentrations of another kidney tubular injury biomarker, kidney injury molecule-1, were below the detectable limit in all but one sample. In conclusion, DSR reduces an established clinical biomarker of kidney tubular damage in adults with moderately elevated SBP who are free from prevalent kidney disease.

This study was performed to determine the effect of ischemic postconditioning on cell apoptosis and angiotensin II receptor type 1 (AT1), connexin 43 (Cx43), and β-tubulin mRNA expression in non-culprit arteries. Non-culprit arterial tissues were isolated from a rabbit myocardial ischemia-reperfusion model and randomly divided into sham, ischemia-reperfusion, and ischemic postconditioning groups. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Expression of angiotensin II, AT1, Cx43, and β-tubulin mRNA was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). TUNEL analysis indicated significantly higher ratios of apoptotic cells in the ischemia-reperfusion group than in the sham group. However, significantly fewer apoptotic cells were observed in the ischemic postconditioning group than in the ischemia-reperfusion group. The qRT-PCR results indicated significantly higher expression of AT1, Cx43, and β-tubulin mRNA in the ischemia-reperfusion group than in the sham group. However, expression of AT1, Cx43, and β-tubulin was lower in the ischemic postconditioning group than in the ischemia-reperfusion group. The ratios of apoptotic cells and mRNA expression of AT1, Cx43, and β-tubulin in non-culprit arteries were increased after ischemia-reperfusion. Ischemic postconditioning may decrease these features and inhibit the progression of non-culprit arteries.

Oral squamous cell carcinoma (OSCC) is a lethal malignancy. It is reportedly demonstrated that long non-coding RNA (lncRNA) participates in the development of OSCC. The purpose of this study was to clarify the function and possible molecular mechanisms of lncRNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) in OSCC. Quantitative real-time PCR (qRT-PCR) was adopted to investigate MCM3AP-AS1 expressions in OSCC tissues and cells. The proliferation, migration and invasion of HN-6 and SCC-9 cells were probed by cell counting kit-8 and Transwell assays, respectively. Dual luciferase reporter gene assay, Pearson's correlation analysis, qRT-PCR and western blot were used to detect the binding relationship among miR-204-5 p, MCM3AP-AS1 and forkheadbox C1 (FOXC1). MCM3AP-AS1 expression was elevated in OSCC tissues and cell lines. Overexpression of MCM3AP-AS1 facilitated the proliferation, migration and invasion of OSCC cells, while the knockdown of MCM3AP-AS1 suppressed these malignant phenotypes. Besides, MCM3AP-AS1 impeded miR-204-5 p by binding with it. MCM3AP-AS1 could also upregulate the expression of FOXC1 via repressing miR-204-5 p. MCM3AP-AS1 promotes the progression of OSCC cells by adsorbing miR-204-5 p and upregulating FOXC1 expressions.

Primary (degenerative) mitral valve (MV) disease is a result of structural remodeling due to degenerative and adaptive changes of MV tissue. We hypothesized that in patients with primary MV disease undergoing surgery for severe mitral regurgitation (MR), a distinct genetic expression profile within the MV leaflet tissue could be identified as compared with patients without MV disease. Tissue samples from the MV leaflets of 65 patients undergoing MV surgery for MR due to primary MV disease and 4 control cadavers without MV disease were collected and analyzed. MicroRNA transcripts were hybridized to Illumina HumanHT-12 v4 Beadchips. Ingenuity pathway analyses (IPAs) were conducted to provide biological interpretation. Of the approximately 20 000 genes examined, 4092 (20%) were differentially expressed between patients with primary MV disease and normal controls (false discovery rate<0.05). The differentially expressed genes could be clustered into five regulator effect networks from the Ingenuity Knowledge IPA database with a consistency score of >6. These five networks have been previously implicated in pathophysiological cardiac abnormalities, including inhibited contractility of the heart and fatty acid oxidation as well as activation of apoptosis of smooth muscle cells, cardiac degeneration, and hypertrophy of cardiac cells. MV tissue in patients with primary MV disease demonstrated distinct genetic expression patterns as compared with normal controls. Further studies are necessary to determine whether the molecular pathways identified in this experiment may represent potential therapeutic targets to prevent degeneration of MV tissue leading to severe MR.

Nowadays, the involvement of the microbiome in human health and many human diseases, including that strictly related to the scalphas been brought to the light. Indeed, more recently, authors highlighted the presence of a significant microbial shift both in nonscarring (Androgenetic alopecia and Alopecia areata) and scarring Alopecias. The advent of novel technologies together with the effort of many scientists in the microbiome field could provide in the nearest future a clearest framework about the strict relationship between human healthiness and symbiotic microorganism resident on different ecosystem of our body. In this view, the use of Omics approaches has to be considered as no longer negligible when studying the microbiome implication in human health and disease.

The biological activity and effects of circulating sphingosine 1-phosphate (S1P) might be dependent on the carrier protein. Although S1P is known to be a biomarker for osteoporotic fracture (OF), its role according to its carrier protein (high-density lipoprotein (HDL), low-density lipoprotein (LDL), or albumin) has not yet been studied. We measured the protein-bound S1P levels and bone mineral density (BMD) in 58 postmenopausal women with OF and 58 age-matched and body mass index-matched postmenopausal women without OF. Albumin-bound S1P was the most abundant. Before adjustment, women with OF had higher total S1P (p=0.046) and albumin-bound S1P (p=0.026) levels than those without OF, but there was no difference in the levels of HDL-bound or LDL-bound S1P. After adjustment for confounders including BMD, women with OF had only higher levels of total S1P than those without OF (p=0.047). Before adjustment, the OR for OF was higher in subjects in the highest quartile for total S1P (OR 5.36, 95% CI 1.22 to 23.63) or albumin-bound S1P (OR 4.48, 95% CI 1.22 to 16.42). After adjustment for confounders including BMD, statistical significance persisted only for total S1P (OR 2.23, 95% CI 1.12 to 4.81). These findings suggest that the positive association of S1P with OF is mainly due to level of total plasma S1P and not due to the differing contributions from specific carrier protein-bound fractions.