Biomedicines

Abstract

Background/Objectives: Cutaneous melanoma (CM) is a highly aggressive malignancy with poor prognosis, necessitating novel biomarkers and therapeutic targets. Centromere protein F (CENPF), a mitotic regulator, has been implicated in tumor progression, but its role in melanoma remains unclear. This study aimed to investigate [...] Read more.

Background/Objectives: Cutaneous melanoma (CM) is a highly aggressive malignancy with poor prognosis, necessitating novel biomarkers and therapeutic targets. Centromere protein F (CENPF), a mitotic regulator, has been implicated in tumor progression, but its role in melanoma remains unclear. This study aimed to investigate the clinical significance, biological function, and regulatory mechanisms of CENPF in melanoma. Methods: Public melanoma datasets (GSE46517, GSE3189, and GSE7553) were re-analyzed to identify differentially expressed genes (DEGs). CENPF expression was validated in clinical samples (n = 128), melanoma cell lines, and xenograft models. Functional assays (EdU, CCK-8, colony formation, wound healing, transwell, and flow cytometry) and bioinformatics analyses (GO, KEGG, GSEA, and SCENIC) were performed to assess proliferation, apoptosis, metastasis, and regulatory pathways. In vivo tumorigenesis and metastasis were evaluated in BALB/c nude mice. Results: CENPF was significantly upregulated in melanoma tissues and cell lines compared to controls (p < 0.05). High CENPF expression correlated with advanced Clark level (p = 0.006), ulceration (p = 0.04), and poor overall survival (p = 0.005). Knockdown of CENPF suppressed melanoma cell proliferation, migration, and invasion in vitro, while inducing G2/M phase arrest and apoptosis. In vivo, CENPF silencing reduced tumor growth and lung metastasis. Mechanistically, CENPF was transcriptionally activated by E2F3, and the E2F3-CENPF axis promoted cell cycle progression via G2/M checkpoint activation and P53 pathway suppression. Conclusions: CENPF serves as a prognostic biomarker and therapeutic target in melanoma. Its upregulation drives tumor progression through cell cycle dysregulation and immune evasion, while targeting the E2F3-CENPF axis may offer a novel strategy for melanoma treatment. These findings provide critical insights into melanoma pathogenesis and potential clinical applications. Full article

Abstract

The skin microbiome, a diverse and dynamic ecosystem of microorganisms, plays a pivotal role in maintaining skin health by interacting with skin cells, immune components, and structural barriers. It is essential for skin homeostasis, immune defense, and protection against pathogenic colonization. Dysbiosis in [...] Read more.

The skin microbiome, a diverse and dynamic ecosystem of microorganisms, plays a pivotal role in maintaining skin health by interacting with skin cells, immune components, and structural barriers. It is essential for skin homeostasis, immune defense, and protection against pathogenic colonization. Dysbiosis in the microbiome has been implicated in numerous dermatological conditions, including acne, eczema, psoriasis, and rosacea. Acne, the most prevalent skin condition, affects up to 85% of individuals at some point in their lives, while eczema and psoriasis impose significant public health and economic burdens. The composition of the skin microbiome varies across skin types and anatomical sites, with sebaceous, moist, and dry areas fostering distinct microbial communities. Emerging therapeutic strategies such as microbiome-targeted treatments offer novel avenues for addressing skin diseases. Among these approaches, postbiotics have gained significant attention for their safety and efficacy. Unlike probiotics, postbiotics are non-viable microbial cells or their metabolites, which reduce safety concerns while providing functional benefits such as UV protection and wound healing. This review consolidates current insights into the role of the skin microbiome in health and disease, emphasizing postbiotics as a promising therapeutic strategy by exploring the clinical and commercial potential of microbiome-based treatments, particularly postbiotics, and their ability to redefine dermatological care and improve patient outcomes. Full article

Abstract

Despite the availability of several drug classes for the treatment of hypertension, the current approaches to high blood pressure (BP) are not fully satisfying the needs of this patient population. As a result, in recent years, many clinical trials have investigated novel pharmacological [...] Read more.

Despite the availability of several drug classes for the treatment of hypertension, the current approaches to high blood pressure (BP) are not fully satisfying the needs of this patient population. As a result, in recent years, many clinical trials have investigated novel pharmacological approaches for lowering high BP. As overactivity of the renin–angiotensin–aldosterone system is often present in hypertensive patients, especially those with resistant hypertension, several studies have focused on novel strategies to counteract this phenomenon by the use of non-steroidal inhibitors of the mineralocorticoid receptors, aldosterone synthase inhibitors or RNA-targeting therapies to inhibit the hepatic synthesis of angiotensinogen. The latter approach in particular might offer the additional advantage of reducing the daily pill burden of these patients, hence mitigating the common occurrence of non-adherence to treatment. Because obesity and diabetes are common risk factors for hypertension (a high percentage of individuals with resistant hypertension being obese), numerous investigations have analyzed the BP-lowering effects of those agents, such as glucagon-like peptide-1 receptor agonists and sodium–glucose co-transporter-2 inhibitors, which have been shown to reduce body weight and improve cardiovascular outcomes in these patients. Available evidence suggests that these drug classes can indeed afford a clinically meaningful BP decrease and, potentially, reduce the treatment burden. In conclusion, even though the rates of uncontrolled hypertension remain high, several novel therapeutic options are in the offing. As these emerging treatments will compound with many already available agents, future efforts should be directed at better phenotyping patients to tailor the most suitable approach for each one. Full article

Abstract

Background/Objectives: Lactate, classically considered a metabolic byproduct of anaerobic glycolysis, is implicated in ischemic acidosis and neuronal injury. The recent evidence highlights its potential role in sustaining metabolic networks and neuroprotection. This study investigates lactate’s compensatory mechanisms in ischemic brain injury by analyzing [...] Read more.

Background/Objectives: Lactate, classically considered a metabolic byproduct of anaerobic glycolysis, is implicated in ischemic acidosis and neuronal injury. The recent evidence highlights its potential role in sustaining metabolic networks and neuroprotection. This study investigates lactate’s compensatory mechanisms in ischemic brain injury by analyzing post-ischemic metabolic enrichments and inter-regional metabolite correlations. Methods: Dynamic metabolic profiling was conducted using ¹³C-labeled glucose combined with ¹H-¹³C NMR spectroscopy to quantify the metabolite enrichment changes in a murine cerebral ischemia model (n = 8). In vivo validation included intracerebroventricular pH-neutral lactate infusion in ischemic mice to assess the behavioral, electrophysiological, and mitochondrial outcomes. In vitro, HT22 hippocampal neurons underwent oxygen–glucose deprivation (OGD) with pH-controlled lactate supplementation (1 mM), followed by the evaluation of neuronal survival, mitochondrial membrane potential, and glycolytic enzyme expression. Results: NMR spectroscopy revealed a 30–50% reduction in most cerebral metabolites post-ischemia (p < 0.05), while the quantities of lactate and the related three-carbon intermediates remained stable or increased. Correlation analyses demonstrated significantly diminished inter-metabolite coordination post-ischemia, yet lactate and glutamate maintained high metabolic activity levels (r > 0.80, p < 0.01). Lactate exhibited superior cross-regional metabolic mobility compared to those of the other three-carbon intermediates. In vivo, lactate infusion improved the behavioral/electrophysiological outcomes and reduced mitochondrial damage. In the OGD-treated neurons, pH-neutral lactate (7.4) reduced mortality (p < 0.05), preserved the mitochondrial membrane potential (p < 0.05), and downregulated the glycolytic enzymes (HK, PFK, and PKM; p < 0.01), thereby attenuating H⁺ production. Conclusions: Under ischemic metabolic crisis, lactate and the three-carbon intermediates stabilize as critical substrates, compensating for global metabolite depletion. pH-neutral lactate restores energy flux, modulates the glycolytic pathways, and provides neuroprotection by mitigating acidotoxicity. Full article

Abstract

Background/Objectives: Genetic factors play an important role in idiopathic rapid eye movement sleep behavior disorder (iRBD) but have not been fully studied. This study aimed to analyze the Parkinson’s disease (PD)-related genetic loci in iRBD in the southern Chinese population. Methods: [...] Read more.

Background/Objectives: Genetic factors play an important role in idiopathic rapid eye movement sleep behavior disorder (iRBD) but have not been fully studied. This study aimed to analyze the Parkinson’s disease (PD)-related genetic loci in iRBD in the southern Chinese population. Methods: In this study, we recruited 292 individuals with PD, 62 with iRBD, and 189 healthy controls (HC). Candidate genes were identified primarily from the Parkinson’s Progression Markers Initiative (PPMI) database. Genotypic and allele frequency analyses were conducted to compare the distribution across HC, iRBD, and PD groups. The effects of significant single-nucleotide polymorphisms (SNPs) on gene expression were examined. Clinical manifestations associated with different genotypes were also analyzed. The receiver operating characteristic (ROC) curve and Kaplan–Meier plots were utilized to further verify the diagnostic and predictive value of these SNPs. Results: We identified two significant SNPs associated with iRBD: rs13294100 of SH3GL2 and rs165599 of COMT. Clinical scale and polysomnography data analysis indicated that iRBD patients with the GA or AA genotype at the COMT rs165599 locus have lower RBDSQ scores and higher sleep efficiency. Moreover, we identified that COMT rs165599 and MCCC1 rs12637471 may play an important role in both PD and iRBD, while SNCA rs356181 was different between iRBD and PD. Conclusions: Our research revealed that in the southern Chinese demographic, genetic loci in SH3GL2 and COMT were linked to iRBD and may act as potential biomarkers for iRBD risk. Additionally, there is evidence suggesting a partial genetic overlap between iRBD and PD, indicating a shared genetic predisposition. Full article

Abstract

Background: Every year, over 40 million people sustain mild traumatic brain injury (mTBI) which affects the glucocorticoid stress pathway and synaptic plasticity. Ketamine, a multimodal dissociative anesthetic, modulates the stress pathway and synaptic plasticity. However, the effects of post-mTBI ketamine administration on plasma [...] Read more.

Background: Every year, over 40 million people sustain mild traumatic brain injury (mTBI) which affects the glucocorticoid stress pathway and synaptic plasticity. Ketamine, a multimodal dissociative anesthetic, modulates the stress pathway and synaptic plasticity. However, the effects of post-mTBI ketamine administration on plasma stress hormones and brain synaptic plasticity are largely unknown. Methods: Adult male Sprague-Dawley rats with indwelling jugular venous catheters sustained mTBI with the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) in a single session (3 impacts × 1.5 J). One hour later, rats received intravenous (IV) ketamine (0, 10, or 20 mg/kg, 2 h). Catheter blood samples were collected for plasma corticosterone and progesterone assays. Brain tissue sections were double-labeled for presynaptic synapsin-1 and postsynaptic density protein 95 (PSD-95). Utilizing the Synaptic Evaluation and Quantification by Imaging Nanostructure (SEQUIN) workflow, super-resolution confocal images were generated, and synapsin-1, PSD-95, and synaptic density were quantified in the CA1 of the hippocampus and medial prefrontal cortex (mPFC). Results: IV ketamine infusion produced biphasic effects on corticosterone levels: a robust elevation during the infusion followed by a reduction after the infusion. CHIMERA injury elevated progesterone levels at post-injury day (PID)-1 and reduced synaptic density in the CA1 at PID-4, regardless of ketamine infusion. Ketamine infusion increased synaptic density in the mPFC at PID-4. Conclusions: Mild TBI and IV ketamine modulate the stress pathway and synaptic plasticity in the brain. Further research is warranted to investigate the functional outcomes of subanesthetic doses of ketamine on stress pathways and neuroplasticity following mTBI. Full article

Abstract

Venous thromboembolism (VTE) is considered the most common and potentially life-threatening cardiovascular complication in cancer and the second leading cause of death after cancer progression itself. In recent years, the steadily increasing rate of cancer-associated thrombosis (CAT) seems mainly related to amelioration in [...] Read more.

Venous thromboembolism (VTE) is considered the most common and potentially life-threatening cardiovascular complication in cancer and the second leading cause of death after cancer progression itself. In recent years, the steadily increasing rate of cancer-associated thrombosis (CAT) seems mainly related to amelioration in imaging techniques and the placements of central venous catheters (CVCs). The pivotal role of CVCs in the switch from hospital to home care is offset by its high thrombotic burden. The peripherally inserted central catheter (PICC) offers advantages (convenience, fast access, and cost-effectiveness) in comparison to centrally inserted devices (PORT), but increased thrombotic risk is reported. The aim of this narrative review was to offer a comprehensive overview of the existing literature about PICC-related thrombosis (PICC-VTE) by analyzing the current knowledge and related gaps. We further discussed advancements in insertion techniques, underscored the role of the novel PICC-PORT lines, and provided a “head-to-head” comparison among major guidelines on primary thromboprophylaxis. Full article

Abstract

Background and Objectives: Negative Pressure Wound Therapy (NPWT) is widely used in acute wound management, promoting tissue regeneration and edema reduction. However, the effects of integrating physiotherapy on functional recovery and quality of life remain underexplored. This study assesses the combined impact [...] Read more.

Background and Objectives: Negative Pressure Wound Therapy (NPWT) is widely used in acute wound management, promoting tissue regeneration and edema reduction. However, the effects of integrating physiotherapy on functional recovery and quality of life remain underexplored. This study assesses the combined impact of NPWT and physiotherapy on functional and clinical outcomes in patients with acute wounds at the Timișoara County Emergency Clinical Hospital. Methods: This cross-sectional study included 205 patients divided into two groups: NPWT-only (n = 110) and NPWT plus physiotherapy (n = 95). Clinical and functional parameters, including joint mobility, edema, and pain, were assessed at baseline, ten days, six weeks, and six months. Quality of life and mental health were evaluated using WHOQOL-BREF, SF-36, VAS, and HADS questionnaires. Results: Compared to NPWT alone, the NPWT + physiotherapy group showed at discharge greater edema reduction (40.58 ± 2.48 vs. 41.15 ± 2.39), improved joint mobility (14.22 ± 1.66° vs. 10.05 ± 1.76°, p < 0.05), and a more significant pain decrease (VAS reduction to 5.68 ± 1.13 vs. 6.7 ± 1.05, p < 0.001). Quality of life scores improved notably, with higher WHOQOL-BREF (59.89 ± 5.86 vs. 66.64 ± 6.24, p < 0.001) and HADS psychological scores (p < 0.001). Conclusions: Combining NPWT with physiotherapy enhances functional recovery, reduces pain and anxiety, and improves quality of life. These findings support a multidisciplinary approach in acute wound management. Full article

Abstract

Background: Elastography is an ultrasound-based imaging technology that allows for quantitative measurement of tissue stiffness and elasticity. In reproductive medicine, it is a potential non-invasive method for assessing ovarian activity, uterine contractility, and endometrial receptivity. While conventional ultrasound provides anatomical and vascular [...] Read more.

Background: Elastography is an ultrasound-based imaging technology that allows for quantitative measurement of tissue stiffness and elasticity. In reproductive medicine, it is a potential non-invasive method for assessing ovarian activity, uterine contractility, and endometrial receptivity. While conventional ultrasound provides anatomical and vascular information, it does not assess biomechanical properties, which are important for understanding polycystic ovary syndrome (PCOS), predicting intrauterine insemination (IUI) success, and determining endometrial receptivity in in vitro fertilization (IVF). Methods: A systematic review was conducted in accordance with the PRISMA principles, and the protocol was recorded in PROSPERO. A comprehensive literature search was conducted across several databases to uncover studies that used real-time elastography (RTE) or shear wave elastography (SWE) for PCOS diagnosis, IUI result prediction, or endometrial receptivity evaluation in IVF. The risk of bias was assessed using the ROBINS-I technique. Results: Four studies fulfilled the inclusion criteria. One study indicated that PCOS patients had considerably increased ovarian stiffness, which supports elastography as a diagnostic marker. Another study found that increased uterine flexibility and decreased contractility were related with better IUI outcomes. A retrospective cohort research discovered that non-uniform endometrial echogenicity had no influence on IVF results. Furthermore, SWE successfully evaluated endometrial receptivity in unexplained infertility, with higher stiffness being related to reduced implantation potential. Conclusions: Elastography gives real-time, quantitative insights into reproductive biomechanics, with potential applications in infertility diagnosis and ART improvement. However, the absence of defined imaging procedures and confirmed clinical criteria prevent its broad use. More large-scale prospective investigations are required to improve elastographic parameters and define diagnostic cutoffs for clinical use. Full article

Abstract

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant dose-limiting side effect of many effective anticancer agents, including vincristine. While CIPN adversely affects both oncological outcomes and the quality of life for cancer patients, the in vivo mechanisms behind CIPN pathology remain largely unknown, [...] Read more.

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant dose-limiting side effect of many effective anticancer agents, including vincristine. While CIPN adversely affects both oncological outcomes and the quality of life for cancer patients, the in vivo mechanisms behind CIPN pathology remain largely unknown, and effective treatments have yet to be developed. In this study, we established a novel Drosophila model of CIPN using vincristine to explore the molecular mechanisms underlying this condition. Methods: We assessed the impact of vincristine exposure on thermal nociception in Drosophila larvae using a programmable heat probe. Additionally, we investigated vincristine-induced mitochondrial dysfunction and dendritic abnormalities in class IV dendritic arborization (C4da) neurons with various fluorescent protein markers. Results: We found a dose-dependent increase in thermal hypersensitivity, accompanied by changes in the sensory dendrites of C4da neurons in vincristine-treated fly larvae. Moreover, vincristine significantly enhanced mitochondrial ROS production and mitophagy—a selective autophagy that targets dysfunctional mitochondria—indicating vincristine-induced mitochondrial dysfunction within C4da neurons. Surprisingly, inhibiting the pyruvate dehydrogenase complex (PDH), a key mitochondrial metabolic enzyme complex, effectively rescued the mitochondrial and sensory abnormalities caused by vincristine. Conclusions: Findings from this first Drosophila model of vincristine-induced peripheral neuropathy (VIPN) suggest that mitochondrial dysfunction plays a critical role in VIPN pathology, representing PDH as a potential target for the treatment of VIPN. Full article

Abstract

Background/Objectives: Marinobufagenin (MBG) is a biomarker that is found to be high in pre-eclampsia (preE), and thus is relevant in the pathogenesis of obstetric complications. MBG is thought to possibly be implicated in harmful signaling within cytotrophoblasts (CTBs) of the placenta. In [...] Read more.

Background/Objectives: Marinobufagenin (MBG) is a biomarker that is found to be high in pre-eclampsia (preE), and thus is relevant in the pathogenesis of obstetric complications. MBG is thought to possibly be implicated in harmful signaling within cytotrophoblasts (CTBs) of the placenta. In this study, we evaluated how anti-MBG human monoclonal antibody can alter cellular signaling in CTBs and in a rat model of preE. Methods: CTB cell proliferation, migration, and invasion as a result of MBG, both with and without anti-MBG present, were monitored via cell-based studies. Pro-angiogenic and anti-angiogenic factors in response to MBG with and without antibody were measured. Finally, we evaluated the lead anti-MBG antibody in comparison with the parent murine antibody in a rat model of preE. Results: CTB cells exposed to ≥1 nM MBG showed decreased (p < 0.05) proliferation, migration, and invasion, decreased secretion of VEGF and PIGF, and increased secretion of sFlt-1 and sEng. Pretreatment with anti-MBG significantly (p < 0.05) attenuated MBG-induced CTB dysfunction and modulation of VEGF, PIGF, sFlt-1, and sEng expression. In the rat model, anti-MBG treatment normalized blood pressure, reduced proteinuria, and eliminated fetal effects. Conclusions: MBG is a potential causative agent for preE, as it causes dysfunction in CTBs due to anti-angiogenic milieu. Our study suggests that anti-MBG antibody binds to MBG, neutralizing it and preventing downstream signaling in vitro. In a rat model of preE, treatment with anti-MBG antibody was effective at normalizing blood pressure, kidney function, and fetal birth weights. These data suggest that a human monoclonal antibody with high specificity and affinity for MBG has potential as a therapeutic agent for preE. Full article

Abstract

Psoriasis is an immune-related disorder that is marked by abnormal thickening of the skin, the rapid multiplication of keratinocytes, and complex interactions between immune cells and the affected areas. Although psoriasis cannot currently be cured, drugs can alleviate symptoms by regulating immune homeostasis [...] Read more.

Psoriasis is an immune-related disorder that is marked by abnormal thickening of the skin, the rapid multiplication of keratinocytes, and complex interactions between immune cells and the affected areas. Although psoriasis cannot currently be cured, drugs can alleviate symptoms by regulating immune homeostasis and preventing comorbidities. There are many types of drugs to treat psoriasis: small-molecule drugs, including corticosteroids; retinoids; vitamin D analogs; and immunosuppressants, such as glucocorticoid ointment, tretinoin cream, methotrexate tablets, etc. Macromolecular biological drugs, such as Certolizumab, Secukinumab, Guselkumab, etc., include monoclonal antibodies that target various inflammatory signaling pathways. Compared with traditional small-molecule drugs, biological therapies offer better targeting and lower systemic side effects, but their high costs and invasive administration modes constrict their widespread use. Spesolimab is the latest biological agent used to target the interleukin-36 receptor (IL-36R) to be approved for market use, which significantly reduces the risk of general pustular psoriasis (GPP) flare by 84%. Additionally, there are several biological agents used to target the interleukin-23/T helper 17 cell pathway that have already entered Phase II and III clinical trials. At present, the first-line therapeutic strategy for mild psoriasis is topical administration. Systemic therapy and phototherapy are preferred for treating moderate to severe types. However, the current therapeutic drugs for psoriasis cannot completely meet the clinical needs. More advanced drug delivery systems with optimized target effects and better bioavailability are required. Nanocarriers are emerging for the delivery of proteins, nucleic acids, and cell-based therapies. In this review, we analyze the current status of psoriasis therapeutics and discuss novel delivery systems for diverse psoriasis drugs, as well as emerging cell-based therapies. We also summarize the therapeutic effectiveness of different delivery strategies. Full article

Abstract

Background: This study integrated four Gene Expression Omnibus (GEO) datasets to identify disease-specific feature genes in head and neck squamous cell carcinoma (HNSCC) through differential expression analysis with batch effect correction. Methods: The GeneCards database was used to find genes related to [...] Read more.

Background: This study integrated four Gene Expression Omnibus (GEO) datasets to identify disease-specific feature genes in head and neck squamous cell carcinoma (HNSCC) through differential expression analysis with batch effect correction. Methods: The GeneCards database was used to find genes related to exosomes, and samples were categorized into groups with high and low expression levels based on these feature genes. Functional and pathway enrichment analyses (GO, KEGG, and GSEA) were used to investigate the possible biological mechanisms underlying feature genes. A predictive model was produced by using machine learning algorithms (LASSO regression, SVM, and random forest) to find disease-specific feature genes. Receiver operating characteristic (ROC) curve analysis was used to assess the model’s effectiveness. The diagnostic model showed excellent predictive accuracy through external data GSE83519 validation. Results: This analysis highlighted 22 genes with significant differential expression. A predictive model based on five important genes (AGRN, TSPAN6, MMP9, HBA1, and PFN2) was produced by using machine learning algorithms. MMP9 and TSPAN6 showed relatively high predictive performance. Using the ssGSEA algorithm, three key genes (MMP9, AGRN, and PFN2) were identified as strongly linked to immune regulation, immune response suppression, and critical signaling pathways involved in HNSCC progression. Matching HNSCC feature gene expression profiles with DSigDB compound signatures uncovered potential therapeutic targets. Molecular docking simulations identified ligands with high binding affinity and stability, notably C5 and Hoechst 33258, which were prioritized for further validation and potential drug development. Conclusions: This study employs a novel diagnostic model for HNSCC constructed using machine learning technology, which can provide support for the early diagnosis of HNSCC and thus contribute to improving patient treatment plans and clinical management strategies. Full article

Abstract

Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These [...] Read more.

Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut–liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD. Full article

Abstract

Background/Objectives: Transforaminal endoscopic lumbar discectomy (TELD) is a minimally invasive spinal surgery known for its effectiveness, lower complication rates, faster recovery, and ability to be performed under local anesthesia. However, foraminal narrowing or access pain during the transforaminal approach can delay or [...] Read more.

Background/Objectives: Transforaminal endoscopic lumbar discectomy (TELD) is a minimally invasive spinal surgery known for its effectiveness, lower complication rates, faster recovery, and ability to be performed under local anesthesia. However, foraminal narrowing or access pain during the transforaminal approach can delay or hinder surgery in patients with far-lateral lumbar disc herniation (LDH). The objectives of this study were to identify predictive factors from preoperative magnetic resonance imaging (MRI) findings and demographics and discuss the optimization of surgical strategies. Methods: This retrospective study included 75 patients with far-lateral LDH who underwent TELD. Preoperative demographics and MRI findings were analyzed. Surgical data, including operative time, length of hospital stay, and intraoperative pain, were recorded. Postoperative outcomes, including complications, revision surgeries, and global outcomes based on the modified Macnab criteria, were evaluated. Preoperative clinical and radiological factors affecting the operative data and results were analyzed. Results: A higher foraminal stenosis grade was significantly correlated with prolonged operative time (p < 0.01) and extended hospital stay (p < 0.01). Extraforaminal LDH was associated with more severe access pain (p < 0.01) owing to increased nerve root irritation. Access pain was significantly correlated with operative time (p < 0.01) and hospital stay (p < 0.01). Appropriate surgical techniques and intraoperative pain management can mitigate these challenges. Conclusions: Preoperative MRI findings, particularly the grade of foraminal narrowing and herniation zone, can predict surgical difficulty and outcomes in TELD for far-lateral LDH. These insights can guide tailored strategies to reduce access pain and improve procedural success under local anesthesia. Full article

Abstract

Background: An imbalance in the vaginal microbiota, often characterized by reduced lactobacilli, paves the way forth for opportunistic bacteria from the gastrointestinal tract. The presence of aerobic bacteria in the genital tract during pregnancy can have negative outcomes on the pregnancy. Peripartum [...] Read more.

Background: An imbalance in the vaginal microbiota, often characterized by reduced lactobacilli, paves the way forth for opportunistic bacteria from the gastrointestinal tract. The presence of aerobic bacteria in the genital tract during pregnancy can have negative outcomes on the pregnancy. Peripartum infections, when not adequately managed, can significantly impact maternal and neonatal health. Antimicrobial resistance poses an escalating global health threat, with newborns particularly vulnerable. Methods: This study constitutes a retrospective observational analysis, encompassing all microbial strains isolated from pregnant women admitted to the “Pius Brînzeu” Clinical County Emergency Hospital in Timișoara, Romania for various infectious diseases over one year. We analyzed 274 samples from 246 pregnant women, of which 242 were cervical samples, 23 urine cultures, 3 wound secretions, 3 amniotic fluids, 1 peritoneal cavity fluid, 1 sputum, and 1 hemoculture. Results: In cervical samples, Group B Streptococcus (GBS) was the most prevalent, representing 42.46% of the isolates. E. coli was the second most frequent at 30.16%, followed by K. pneumoniae at 11.9%, S. aureus at 8.73%, C. albicans at 2.78%, and other species at 3.97%. A total of 9.63% of cervical GBS isolates exhibited resistance to penicillin, while 23.36% were identified as multi-drug resistant (MDR). Methicillin-resistant S. aureus (MRSA) and MDR S. aureus strains were identified in 50% and 54.54% of the S. aureus-positive cervical samples, respectively. Conclusions: Recognizing the implications of maternal infection or colonization, especially with antimicrobial resistance bacteria, aids in assessing risks during pregnancy. Full article

Abstract

Background/Objectives: Artificial intelligence (AI) is rapidly transforming the landscape of modern medicine, offering advanced tools for diagnosing complex conditions. In the realm of venous pathologies such as chronic venous disease (CVD), venous reflux, and deep venous thrombosis (DVT), AI has shown tremendous [...] Read more.

Background/Objectives: Artificial intelligence (AI) is rapidly transforming the landscape of modern medicine, offering advanced tools for diagnosing complex conditions. In the realm of venous pathologies such as chronic venous disease (CVD), venous reflux, and deep venous thrombosis (DVT), AI has shown tremendous potential to improve diagnostic accuracy, streamline workflows, and enhance clinical decision-making. This study aims to evaluate the efficacy and feasibility of AI algorithms in diagnosing venous diseases and explore their potential impact on clinical practice. Methods: This paper provides a comprehensive review of key studies documenting the use of AI in venous pathology diagnostics, with different electronic databases being searched, including MEDLINE/Pub Med, Web of Science, Scopus, Embase, ResearchGate, and Google Scholar. Results: Out of 52 reports assessed for eligibility, 43 were excluded according to the preset criteria; therefore, findings from nine major studies involving more than 1000 patients were analyzed. The evaluation shows that AI utilization in the diagnosis of venous pathologies has demonstrated significant improvements. Notably, AI algorithms have achieved an accuracy exceeding 90%, significantly reducing inter-observer variability and ensuring consistent interpretation of ultrasonographic images across different clinicians and settings. Additionally, AI has accelerated diagnostic workflows, decreasing the time required for image analysis by more than 50%. Furthermore, AI has proven capable of detecting subtle abnormalities, such as minor venous reflux or early-stage thrombi, which may be overlooked during manual evaluations. Conclusions: Artificial intelligence represents a transformative innovation in the diagnosis and management of venous diseases. By enhancing diagnostic accuracy, streamlining workflows, and enabling personalized care, AI has the potential to address current challenges in venous diagnostics and improve patient outcomes. The future of AI in venous diagnostics is promising, and several areas of development were noted, including AI algorithms embedding directly into ultrasound devices to provide instantaneous diagnostic insights during patient evaluations; combining AI-processed Doppler data with other imaging modalities, such as computed tomography or MRI, for comprehensive assessments; AI usage in order to predict disease progression and tailor treatment strategies based on individual patient profiles; and constructing large-scale, multicenter datasets to improve the robustness and generalizability of AI algorithms. Full article

Abstract

Immune-mediated inflammatory diseases (IMIDs) are characterized by chronic systemic inflammation and multi-organ involvement. Fibrosis formation in IMIDs can cause tissue destruction and subsequently organ malfunction. Fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPi PET/CT) represents a novel imaging technique that holds great [...] Read more.

Immune-mediated inflammatory diseases (IMIDs) are characterized by chronic systemic inflammation and multi-organ involvement. Fibrosis formation in IMIDs can cause tissue destruction and subsequently organ malfunction. Fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPi PET/CT) represents a novel imaging technique that holds great potential to visualize in vivo fibrosis. We here provide an overview of available evidence on FAPi PET/CT imaging to visualize fibrosis in various IMIDs, including interstitial lung diseases, immunoglobulin G4-related diseases, cardiovascular diseases, kidney diseases, and gastrointestinal diseases. FAPi PET/CT imaging demonstrates high sensitivity in detecting early fibrosis, correlating with disease severity, across different IMIDs, showing superiority compared to conventional imaging modalities. Although FAPi PET/CT might be a useful tool to assess fibrosis formation, thereby aiding in grading disease severity and staging, future studies should include larger sample sizes in a broad variety of IMIDs with emphasis on the optimization of imaging protocols to further validate its diagnostic value. Full article

Abstract

Background/Objectives: Diabetes is the most prevalent metabolic disease globally, characterized by dysregulated glucose control and accompanied by multiple refractory complications. As a critical marker of cellular homeostasis, telomere length (TL) may be associated with the progression of diabetes. However, the causal relationship between [...] Read more.

Background/Objectives: Diabetes is the most prevalent metabolic disease globally, characterized by dysregulated glucose control and accompanied by multiple refractory complications. As a critical marker of cellular homeostasis, telomere length (TL) may be associated with the progression of diabetes. However, the causal relationship between diabetes and TL remains unclear, particularly whether cellular homeostasis imbalance acts as a consequence of diabetic complications or a precipitating factor in disease development. Methods: We performed a bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. Following the three core assumptions of MR analysis, we conducted quality control on all instrumental variables to ensure methodological rigor. The inverse variance weighted (IVW) method served as the primary analytical method, supplemented by additional MR methods to evaluate the significance of the results. Furthermore, we performed sensitivity analyses to ensure the reliability and robustness of the findings. Results: Forward analysis revealed that shortened TL significantly increases the risk of broadly defined Type 1 diabetes (T1D) and unspecified types of diabetes (p < 0.05). Additionally, we identified a positive causal relationship between TL and several diabetes-related complications, including co-morbidities, diabetic nephropathy, and diabetic ketoacidosis (p < 0.05). Interestingly, the reverse analysis demonstrated a positive causal effect of T1D and its complications on TL (p < 0.05); however, this effect disappeared after adjusting for insulin use (p > 0.05). Conclusions: Bidirectional MR analyses revealed a complex relationship between TL and T1D, where shortened telomeres increase T1D risk while T1D itself may trigger compensatory mechanisms affecting telomere maintenance, with insulin playing a crucial regulatory role in this relationship. These findings suggest telomere biology may be fundamentally involved in T1D pathogenesis and could inform future therapeutic approaches. Full article