Exploring miRNA Biomarkers in Major Depressive Disorder: A Molecular Medicine Perspective.

Major depressive disorder (MDD) is a complex mental health condition with a multifaceted and incompletely elucidated pathophysiology. MicroRNAs (miRNAs) have emerged as potential biomarkers due to their role in gene regulation and the observed dysregulation in MDD. The aim of this study is to detect the presence of specific molecular diagnostic biomarkers in major depressive disorder. This cross-sectional study analyzed plasma miRNA expression in ten MDD patients and eight healthy controls using real-time PCR. Differentially expressed miRNAs were identified using independent t-tests, and their diagnostic potential was assessed with ROC curve analysis. Fifteen miRNAs exhibited significant dysregulation in MDD patients. Notably, hsa-miR-29c-3p, hsa-miR-376a-3p, hsa-miR-532-5p, and hsa-miR-339-5p showed excellent discriminatory power (AUC > 0.8). This study identifies differentially expressed plasma miRNAs in MDD, suggesting their potential for improved diagnosis and personalized treatment. However, further validation in larger cohorts and investigation into their functional roles are warranted.

Identification of Specific Plasma miRNAs as Potential Biomarkers for Major Depressive Disorder.

BACKROUND: Depression is a significant concern in clinical and preclinical psychoneurobiological sciences due to its high prevalence and its individual and collective consequences. Identifying efficient biomarkers for accurate diagnosis is crucial, with ideal biomarkers having detectable serum levels and conformational and thermal stability. This study aims to identify stable plasma biomarkers for the diagnosis and prognosis of major depressive disorder, as the pathogenesis of the disorder remains incompletely understood, affecting diagnosis accuracy. METHODS: Thus, this study included ten MDD patients and eight healthy controls. The present work analyzed miRNAs in patients with major depressive disorder compared to healthy controls. RESULTS: Eleven specific miRNAs, particularly hsa-miR-874-3p; hsa-let-7d-5p; and hsa-miR-93-3p showed upregulation-type plasma variations in the group of patients with major depressive disorder. miRNA functionality is linked to depressive pathophysiology. CONCLUSIONS: This study identifies a "bouquet" of miRNAs with significant upregulation variations in patients with major depressive disorder, suggesting further research to determine their suitability for personalization and evaluation, ultimately becoming integral components of major depression serological evaluations.

Exploring the Preventive Potential of Vitamin D against Respiratory Infections in Preschool-Age Children: A Cross-Sectional Study.

Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This cross-sectional study, conducted from May 2022 to December 2023 in Timisoara, Romania, aimed to evaluate the potential influence of vitamin D supplementation on the incidence of respiratory infections among preschool-age children. This study examined 215 children over 18 months who were split into a group of patients with recurrent respiratory infections (n = 141) and another group of patients with only one respiratory tract infection in the past 12 months (n = 74). Patients were evaluated based on their serum vitamin D levels 25(OH)D, demographic characteristics, and health outcomes. The study identified that preschool-age children with recurrent infections had significantly lower mean vitamin D concentrations (24.5 ng/mL) compared to the control group (29.7 ng/mL, p < 0.001). Additionally, a higher proportion of vitamin D deficiency was observed among children with recurrent infections in the past 12 months. Notably, vitamin D supplementation above 600 IU/week significantly reduced the likelihood of respiratory infections, evidenced by an odds ratio of 0.523 (p < 0.001), indicating that preschool-age children receiving a dose of vitamin D higher than 600 IU/week were about half as likely to experience respiratory infections compared to those who did not. Furthermore, no significant associations were found between sun exposure, daily sunscreen use, and the incidence of respiratory infections. Conclusively, this study underscores the potential role of vitamin D in helping the immune system against respiratory infections in preschool-age children. The observed protective effect of vitamin D supplementation suggests a potential public health strategy to mitigate the incidence of respiratory infections in preschool children on top of the already known benefits.

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review.

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes.

Surgical Treatment of Lithiasis of the Main Pancreatic Duct: A Challenging Case and a Literature Review.

Pancreaticolithiasis represents a rare phenomenon, being superimposed most of the time on a form of chronic pancreatitis of multifactorial etiology. Pancreaticolithiasis is a late complication of the phenomenon of chronic pancreatitis. The reverberant inflammatory process, followed by the fibrotic degeneration of the pancreatic parenchyma, and pancreatic fluid stasis at the ductal level are factors that contribute to the phenomenon of calcium precipitation. This article describes the case of a patient with a diagnosis of pancreaticolithiasis (Wirsung duct lithiasis), a phenomenon superimposed on chronic pancreatitis of ethanolic cause (Rosemont classification). It was decided to perform surgery via the classical approach with the perfection of corporeo-caudal pancreatectomy and preservation of the splenic vessels (Kimura procedure) with pancreatico-jejunal anastomosis on the Roux-en-Y loop. The aim of this study is to identify the best method of treatment for pancreaticolithiasis. To enhance the case and provide a basis for standardization, a literature review was carried out, which included a total of six articles. The results of this study highlight that, currently, the management of symptomatic pancreaticolithiasis encompasses medical therapy (enzyme replacement therapy), interventional therapy (ESWL (extracorporeal shock wave lithotripsy) ± ERCP (endoscopic retrograde cholangiopancreatography), ERCP + sphincterotomy + stent insertion, and POP (oral pancreatoscopy)), and surgical treatment. In conclusion, based on the analysis conducted in this study, the size of the calculi present determines which is the suitable therapeutic care. Unlike stones over 0.5 cm, when surgery is explicitly advised for therapeutic purposes in the absence of endoscopic techniques, stones under 0.5 cm should be treated using endoscopic procedures.

Utility of Kansas City Cardiomyopathy Questionnaire (KCCQ) in Assessing Quality of Life among Patients with Heart Failure Undergoing Exercise Training Rehabilitation: A Systematic Review.

This systematic review evaluates the effectiveness of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in assessing quality of life improvements among patients with heart failure (HF) undergoing various forms of exercise training rehabilitation, including telemedicine and in-person modalities, across all stages of HF, irrespective of ejection fraction (EF) and clinical status. The aim was to collate evidence from studies employing the KCCQ as a measure of quality of life (QoL). A comprehensive search strategy was implemented across PubMed, Scopus, and Embase databases, adhering to the PRISMA guidelines, including literature up until October 2023. Inclusion criteria encompassed studies on patients diagnosed with HF undergoing exercise training rehabilitation assessed by KCCQ. Nine articles met the inclusion criteria, involving a total of 3905 patients from various global locations and conducted between 2012 and 2022. Results indicated significant heterogeneity in exercise interventions and patient characteristics. Notably, high-intensity interval training (HIIT) showed a marked improvement in KCCQ scores (from 68.0 to 80.0) compared to moderate continuous training (MCT) and control groups, underscoring its potential for enhancing QoL. Additionally, a significant improvement in the 6-min walking test (6MWT) outcomes was observed, with an average increase of 106 m (95% CI: 60, 152) in one study, reflecting physical capacity enhancements. However, the difference in KCCQ scores between intervention and control groups was not statistically significant in several studies. In conclusion, the KCCQ's effectiveness is highlighted by its ability to detect clinically meaningful improvements in QoL across diverse exercise modalities, including HIIT and MCT, tailored to the specific needs of HF populations. The consistent correlation between KCCQ score improvements and enhanced physical outcomes, such as the 6MWT, supports its reliability in capturing the nuanced benefits of exercise interventions on patient well-being.

The Predictive Role of Serum Lipid Levels, p53 and ki-67, According to Molecular Subtypes in Breast Cancer: A Randomized Clinical Study.

Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) (p < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume (p = 0.002) and increased level of HDL (p = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS.

Evaluating the Connection between MicroRNAs and Long Non-Coding RNAs for the Establishment of the Major Depressive Disorder Diagnosis.

The most prevalent mental illness worldwide and the main contributor to suicide and disability is major depressive disorder. Major depressive disorder is now diagnosed and treated based on the patient's statement of symptoms, mental status tests, and clinical behavioral observations. The central element of this review is the increased need for an accurate diagnostic method. In this context, the present research aims to investigate the potential role of two non-coding RNA species (microRNA and long non-coding RNA) in peripheral blood samples and brain tissue biopsy from patients with major depressive disorder. This study reviewed the literature on microRNA and long non-coding RNA expression in blood and brain tissue samples in human and animal depression models by retrieving relevant papers using the PubMed database. The results reveal significant variations in microRNA and long non-coding RNA levels in depressed patients, making it a crucial diagnostic tool that predicts treatment outcomes. It can help track severe cases and adjust therapy dosages based on treatment responses. In conclusion, microRNAs and long non-coding RNAs are pertinent biomarkers that can be added to the diagnostic test panel for major depressive disorder. Both microRNAs and non-coding RNAs can also be used as a tool to track patient progress during therapy and to assist the attending physician in tracking the molecular development of the disease.

A Preliminary Report Regarding the Morphological Changes of Nano-Enabled Pharmaceutical Formulation on Human Lung Carcinoma Monolayer and 3D Bronchial Microtissue.

Background and Objectives: Nowadays, the development of enabled pharmaceutical nanoparticles of solid lipid type is continuously growing, because they have the potential to be used for targeted drug release leading to an increased effect of chemotherapy, being used in lung cancer nano-diagnosis and nano-therapy. The current study reports the preliminary results obtained regarding the biological effect of a new nano-enabled pharmaceutical formulation in terms of its cytotoxic and biosafety profile. Materials and Methods: The pharmaceutical formulations consist of solid lipid nanoparticles (SLN) obtained via the emulsification-diffusion method by loading green iron oxide nanoparticles (green-IONPs) with a pentacyclic triterpene (oleanolic acid-OA). Further, a complex biological assessment was performed, employing three-dimensional (3D) bronchial microtissues (EpiAirwayTM) to determine the biosafety profile of the SLN samples. The cytotoxic potential of the samples was evaluated on human lung carcinoma, using an in vitro model (A549 human lung carcinoma monolayer). Results: The data revealed that the A549 cell line was strongly affected after treatment with SLN samples, especially those that contained OA-loaded green-IONPs obtained with Ocimum basilicum extract (under 30% viability rates). The biosafety profile investigation of the 3D normal in vitro bronchial model showed that all the SLN samples negatively affected the viability of the bronchial microtissues (below 50%). As regards the morphological changes, all the samples induce major changes such as loss of the surface epithelium integrity, loss of epithelial junctions, loss of cilia, hyperkeratosis, and cell death caused by apoptosis. Conclusions: In summary, the culprit for the negative impact on viability and morphology of 3D normal bronchial microtissues could be the too-high dose (500 µg/mL) of the SLN sample used. Nevertheless, further adjustments in the SLN synthesis process and another complex in vitro evaluation will be considered for future research.

Analysis of Vaginal Microbiota Variations in the Third Trimester of Pregnancy and Their Correlation with Preterm Birth: A Case-Control Study.

This study conducted a detailed analysis of the vaginal microbiota in pregnant women to explore its correlation with preterm birth (PTB) outcomes. The primary objective was to identify microbial variations associated with increased PTB risk. Secondary objectives included investigating how changes in microbial composition relate to the local immune environment and PTB. Utilizing a retrospective case-control design, the study involved pregnant women with liveborn infants between 2019 and 2023. In total, 89 women who delivered preterm and 106 term deliveries were included. Data collection focused on third-trimester vaginal cultures. Statistically significant differences were observed between the preterm and full-term groups in several areas. The median white blood cell count (10.2 × 103/mm3 vs. 7.6 × 103/mm3, p = 0.009) and neutrophil count (7.2 × 103/mm3 vs. 5.1 × 103/mm3, p < 0.001) were higher in the preterm group. Vaginal pH was also elevated in preterm births (5.6 vs. 4.4, p < 0.001), with a higher prevalence of bacterial vaginosis (29.2% vs. 12.3%, p = 0.001) as indicated by the Nugent Score. The study noted a significant association of PTB with the presence of Candida spp. (OR = 1.84, p = 0.018), Gardnerella vaginalis (OR = 2.29, p = 0.003), Mycoplasma hominis (OR = 1.97, p = 0.007), and Ureaplasma urealyticum (OR = 2.43, p = 0.001). Conversely, a reduction in Lactobacillus spp. correlated with a decreased PTB risk (OR = 0.46, p = 0.001). The study provides compelling evidence that specific vaginal microbiota components, particularly certain pathogenic bacteria and an altered Lactobacillus profile, are significantly associated with PTB risk. These findings highlight the potential of targeting microbial factors in strategies aimed at reducing PTB rates. Further research is necessary to fully understand the complex interplay between microbial dynamics, host immunity, and PTB outcomes.

Current Trends in Diagnosis and Treatment Approach of Diabetic Retinopathy during Pregnancy: A Narrative Review.

Diabetes mellitus during pregnancy and gestational diabetes are major concerns worldwide. These conditions may lead to the development of severe diabetic retinopathy during pregnancy or worsen pre-existing cases. Gestational diabetes also increases the risk of diabetes for both the mother and the fetus in the future. Understanding the prevalence, evaluating risk factors contributing to pathogenesis, and identifying treatment challenges related to diabetic retinopathy in expectant mothers are all of utmost importance. Pregnancy-related physiological changes, including those in metabolism, blood flow, immunity, and hormones, can contribute to the development or worsening of diabetic retinopathy. If left untreated, this condition may eventually result in irreversible vision loss. Treatment options such as laser therapy, intravitreal anti-vascular endothelial growth factor drugs, and intravitreal steroids pose challenges in managing these patients without endangering the developing baby and mother. This narrative review describes the management of diabetic retinopathy during pregnancy, highlights its risk factors, pathophysiology, and diagnostic methods, and offers recommendations based on findings from previous literature.

Longitudinal Assessment of Facial Hyperhidrosis Management: Evaluating the Utility and Quality of Life Improvements following Botulinum Toxin Injection.

Facial hyperhidrosis is a debilitating condition that can severely impact the quality of life. This study aimed to assess the long-term utility of Botulinum toxin type A therapy (BTA) for facial hyperhidrosis and its impact on quality of life over a one-year period. Conducted at the Pius Brinzeu Clinical Emergency Hospital in Timisoara, Romania, this longitudinal observational study involved 77 adult patients with primary facial hyperhidrosis. Participants received two sessions of Botulinum toxin injections (50 U IncoBTX-A each) and were evaluated at baseline, 6 months, and 12 months using the Hyperhidrosis Disease Severity Scale (HDSS), WHOQOL-BREF, Dermatology Life Quality Index (DLQI), and a bespoke survey. The study demonstrated significant reductions in HDSS scores from 3.6 ± 0.5 to 1.2 ± 0.8 post-treatment, sustained at 1.3 ± 0.6 at 12 months (p-value < 0.001). DLQI scores markedly decreased from 24.8 ± 4.2 to 6.2 ± 2.1 post-treatment, stabilizing at 6.5 ± 2.5 at 12 months (p-value < 0.001). Sweat production significantly dropped from 0.75 g ± 0.15 to 0.18 g ± 0.07 per 15 min (p-value < 0.001). WHOQOL-BREF scores improved notably in the mental domain from 66.7 ± 6.1 to 70.8 ± 5.2 at 12 months (p-value < 0.001), with physical and social domains also showing significant improvements. Correlation analysis revealed strong negative correlations between DLQI total score and HDSS (rho = -0.72, p-value < 0.001) and sweat production (rho = -0.68, p-value < 0.001). Regression analysis indicated significant predictors for DLQI total score, including HDSS (B Coefficient = -3.8, p-value < 0.001) and sweat production (B Coefficient = -2.2, p-value < 0.001). BTA therapy significantly improved the quality of life in facial hyperhidrosis patients, with lasting effects on symptom severity, sweat production, and quality of life domains. The correlation and regression analyses further substantiated the treatment's impact on both physical and psychological aspects. These findings advocate Botulinum toxin as a viable long-term treatment for facial hyperhidrosis.

The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes.

INTRODUCTION: The antitumor host immune response is an important factor in breast cancer, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) as an immunological biomarker in breast cancer has been significantly explored in recent years. The number of patients treated with neoadjuvant chemotherapy (NAC) has increased and the identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority. MATERIALS AND METHODS: We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020-2022 at the Ist Clinic of Oncological Surgery, Oncological Institute "Prof Dr I Chiricuta" Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts were performed using hematoxylin eosin (H&E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG). RESULTS: There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype and the number of mitoses (p < 0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis (p < 0.005). We also demonstrated that high pre-NAC STIL represents a strong predictive marker for pCR. CONCLUSION: This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of sTIL as a novel predictive and therapy-predicting factor should become a routinely performed analysis that could guide clinicians when choosing the most appropriate therapy.