The Influence of COVID-19 in Glycemic Control: Predictive Value of Inflammation and Metabolic Parameters
Predicting post-COVID-19 diabetes is crucial for enhancing patient care and public health. This study investigates the role of metabolic factors in predicting the glycemic outcomes in patients recovering from moderate to severe COVID-19.
Gallic Acid Induces HeLa Cell Lines Apoptosis via the P53/Bax Signaling Pathway
Cervical cancer is a type of cancer that originates from the endometrium and is more common in developed countries and its incidence is increasing day by day in developing countries. The most commonly prescribed chemotherapeutic drugs limit their use due to serious side effects and the development of drug resistance. For this reason, interest in new active ingredients obtained from natural products is increasing. This study aimed to reveal the apoptotic and antiproliferative effects of gallic acid and doxorubicin combination therapy against the HeLa cell line.
Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)-A Pilot Study
Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). : Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 ( = 0.012), IL-12 ( = 0.049) and anti-inflammatory IL-10 ( = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients.
Disease Modifying Monoclonal Antibodies and Symptomatic Pharmacological Treatment for Alzheimer's Disease
Alzheimer's Disease (AD) is an irreversible, progressive syndrome characterized by neurocognitive impairment. Two neuropathological features seen in AD are extracellular amyloid plaques consisting of amyloid beta1-40 and 1-42, and intracellular neurofibrillary tangles (NFTs). For decades, neuroscience research has heavily focused on seeking to understand the primary mechanism of AD and searching for pharmacological approaches for the treatment of dementia. Three monoclonal antibodies that act against amyloid beta-aducanumab, lecanemab, and donanemab-have been approved by the Food and Drug Administration (FDA) for the treatment of mild cognitive impairment and mild AD, in addition to medications for cognitive symptom management such as acetylcholinesterase inhibitors and the N-methyl-D-aspartate (NMDA) antagonist. Further trials should focus on the combination of therapies targeting amyloid plaques and tau pathology.
Severe Malaria in Angola: The Clinical Profile and Disease Outcome Among Adults from a Low-Endemic Area
Severe malaria poses a significant public health concern in Angola, particularly among adults. This study assessed the clinical manifestations and outcomes of severe malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango (HCL), Angola.
Advanced Parameters of Myocardial Strain and Cardiac Biomarkers Indicate Subclinical Systolic Myocardial Dysfunction in Patients with Systemic Lupus Erythematous
: Systemic lupus erythematosus (SLE) is characterized by inflammation and cardiovascular complications. Our study aimed to investigate subclinical and early indicators of systolic myocardial dysfunction in SLE patients using advanced echocardiographic methods and biomarkers. : In this cross-sectional study, we enrolled 102 SLE patients without known cardiac impairment and 51 healthy controls. Demographics, disease characteristics, laboratory results, disease activity (SLEDAI), and organ damage (SDI) indices were recorded. Left ventricular global longitudinal strain (GLS) and myocardial work indices were assessed by utilizing speckle tracking echocardiography. In addition, high-sensitivity C-reactive protein (hsCRP), high-sensitivity troponin (hsTn), and N-terminal-pro B-type natriuretic peptide (NT-proBNP) levels were measured in blood samples. : In comparison with controls, SLE patients had significantly higher GLS (-19.94 ± 2.71% vs. -21.15 ± 1.55%, < 0.001) and global wasted work (GWW) (94 ± 71 mmHg% vs. 71 ± 49 mmHg%, = 0.025). Notably, NT-proBNP and hsTn were threefold and twofold higher in the SLE group compared with the control group, respectively ( < 0.001). Within the SLE cohort, in patients with at least moderate disease activity (SLEDAI ≥ 4), both biomarkers were significantly more elevated than those with low disease activity (SLEDAI < 4). Notably, hsTn levels remained within the normal range. : Advanced echocardiographic parameters combined with specific biomarkers have a promising role in detecting systolic dysfunction in SLE patients, potentially enabling timely interventions to mitigate cardiovascular risk.
Involvement of /Galectin-3 in Choroidal Neovascularization and Subretinal Fibrosis Formation
/galectin-3 plays a pivotal role in many vascular diseases. However, the involvement of /galectin-3 in eyes with neovascular age-related macular degeneration (nAMD) remains unknown. In the laser-induced CNV model, a whole mount retina stained with Isolectin B4 and collagen type I revealed the vascular bed and CNV-associated subretinal fibrosis on day 7 after laser treatment. We show that the expression levels of /galectin-3 were significantly increased in the RPE/choroidal complex of CNV mice. An intravitreal injection of -siRNA significantly suppressed the area of CNV and subretinal fibrosis, together with decline. The mixture of -siRNA and Ranibizumab showed more efficiency than each drug used separately. Hypoxia induced /galectin-3 production in ARPE-19 cells, which was reduced by the silencing hypoxia-inducible factor -1α (). Our data indicated that /galectin-3 is involved in the pathogenesis of CNV and subretinal fibrosis, and /galectin-3 could be a potential therapeutic target for nAMD.
Prognostic Significance and Immune Landscape of a Cuproptosis-Related LncRNA Signature in Ovarian Cancer
Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. A series of statistical analyses were used to identify the key CRLs that are closely related to the prognosis, and a prognostic CRlncSig was constructed. The predictive accuracy of the CRlncSig was further validated in an independent Gene Expression Omnibus (GEO) set. Then, we compared the immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor mutational burden (TMB), drug sensitivity, and efficacy of immunotherapy between the two subgroups. We further built a nomogram integrating the CRlncSig and different clinical traits to enhance the clinical application of the CRlncSig. Nine hub CRLs, namely RGMB-AS1, TYMSOS, DANCR, LINC00702, LINC00240, LINC00996, DNM1P35, LINC00892, and TMEM254-AS1, were correlated with the overall survival (OS) of OC and a prognostic CRlncSig was established. The CRlncSig classified OC patients into two risk groups with strikingly different survival probabilities. The time-dependent ROC (tdROC) curves demonstrated good predictive ability in both the training cohort and an independent validation cohort. Multivariate analysis confirmed the independent predictive performance of the CRlncSig. We constructed a nomogram based on the CRlncSig, which can predict the prognosis of OC patients. The high-risk score was characterized by decreased immune cell infiltration and activation of stroma, while activation of immunity was observed in the low-risk subgroup. Moreover, patients in low-risk subgroups had more Immunophenoscore (IPS) and fewer immune escapes compared to high-risk subgroups. Finally, an immunotherapeutic cohort confirmed the value of the CRlncSig in predicting immunotherapy outcomes. The developed CRlncSig may be promising for the clinical prediction of OC patient outcomes and immunotherapeutic responses.
Molecular Basis for the Differential Function of HAVCR1 Mucin Variants
: The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1) is a type I integral membrane glycoprotein discovered in monkeys and humans as a HAV receptor. HAVCR1 contains an N-terminal immunoglobulin-like variable domain (IgV) followed by a mucin-like domain (Muc), a transmembrane domain, and a cytoplasmic tail with a canonical tyrosine kinase phosphorylation site. The IgV binds phosphatidylserine on apoptotic cells, extracellular vesicles, and enveloped viruses. Insertions/deletions at position 156 (156ins/del) of the Muc were associated in humans with susceptibility to atopic, autoimmune, and infectious diseases. However, the molecular basis for the differential function of the HAVCR1 variants is not understood. : We used mutagenesis, apoptotic cell binding, and signal transduction analyses to study the role of the 156ins/del in the function of HAVCR1. : We found that the HAVCR1 variant without insertions at position 156 (156delPMTTTV, or short-HAVCR1) bound more apoptotic cells than that containing a six amino acid insertion (156insPMTTTV, or long-HAVCR1). Furthermore, short-HAVCR1 induced stronger cell signaling and phagocytosis than long-HAVCR1. : Our data indicated that the 156ins/del determine how the IgV is presented at the cell surface and modulate HAVCR1 binding, signaling, and phagocytosis, suggesting that variant-specific targeting could be used as therapeutic interventions to treat immune and infectious diseases.
Selective Serotonin Reuptake Inhibitors for Cessation of Betel Quid Use in Patients with Major Depressive Disorder in Taiwan
: Major depressive disorder (MDD) frequently co-occurs with substance use disorders such as alcohol and nicotine use disorders. Comorbid substance use disorders worsen the clinical symptoms of MDD and exacerbate addictive behaviors and presentations. However, the relationship between MDD and betel quid use disorder (BUD) in Taiwan has not been extensively investigated. : We performed this cross-sectional study investigated associations between betel quid use, BUD, and MDD specifically in the Taiwanese population. Long-term betel quid use is a major public health concern, contributing significantly to the high incidence of oral cancers, which rank fifth among the top ten most common cancers in Taiwan. : Among patients with MDD, the current BUD prevalence rate was 7.32%, and the lifetime BUD prevalence rate was 15.45%. Patients with comorbid BUD were more likely to have severe alcohol and nicotine dependence disorders and required longer antidepressant treatment. : Notably, 16.98% of patients with comorbid BUD who received selective serotonin reuptake inhibitor treatment achieved abstinence. BUD has a detrimental effect on health outcomes in patients with MDD, and selective serotonin reuptake inhibitor treatment may be required to be prolonged for betel quid abstinence therapy to be effective. Additional studies should investigate medication therapies for betel quid addiction disorders.
Multi-Algorithm-Integrated Tertiary Lymphoid Structure Gene Signature for Immune Landscape Characterization and Prognosis in Colorectal Cancer Patients
Colorectal cancer (CRC) is a common malignancy with a low survival rate as well as a low response rate to immunotherapy. This study aims to develop a risk model based on tertiary lymphoid structure (TLS)-associated gene signatures to enhance predictions of prognosis and immunotherapy response.
Advancements in Autophagy Modulation for the Management of Oral Disease: A Focus on Drug Targets and Therapeutics
Autophagy is an intrinsic breakdown system that recycles organelles and macromolecules, which influences metabolic pathways, differentiation, and thereby cell survival. Oral health is an essential component of integrated well-being, and it is critical for developing therapeutic interventions to understand the molecular mechanisms underlying the maintenance of oral homeostasis. However, because of the complex dynamic relationship between autophagy and oral health, associated treatment modalities have not yet been well elucidated. Determining how autophagy affects oral health at the molecular level may enhance the understanding of prevention and treatment of targeted oral diseases. At the molecular level, hard and soft oral tissues develop because of complex interactions between epithelial and mesenchymal cells. Aging contributes to the progression of various oral disorders including periodontitis, oral cancer, and periapical lesions during aging. Autophagy levels decrease with age, thus indicating a possible association between autophagy and oral disorders with aging. In this review, we critically review various aspects of autophagy and their significance in the context of various oral diseases including oral cancer, periapical lesions, periodontal conditions, and candidiasis. A better understanding of autophagy and its underlying mechanisms can guide us to develop new preventative and therapeutic strategies for the management of oral diseases.
Untangling Depression in Schizophrenia: The Role of Disorganized and Obsessive-Compulsive Symptoms and the Duration of Untreated Psychosis
Schizophrenia is a complex disorder characterized by positive symptoms (e.g., hallucinations), negative symptoms (e.g., social withdrawal), and disorganized symptoms (e.g., thought disorder). Alongside these, cognitive and depressive symptoms often emerge, with depressive symptoms sometimes dominating the clinical picture. Understanding the factors that influence the development of depressive symptoms in schizophrenia could clarify the dynamics between depressive and psychotic symptoms and guide clinical interventions. A total of 105 patients with schizophrenia (66 women, 39 men) were assessed using several clinical scales: PANSS, BPRS, DOCS, DES, HAM-D, and the Luria-Nebraska Neuropsychological Battery for cognitive evaluation. Statistical analyses, including correlation and regression, were conducted using SPSS to determine the significance of associations. Disorganized and obsessive-compulsive symptoms were identified as primary factors associated with depressive symptoms in patients with schizophrenia. Conversely, a longer duration of untreated psychosis was linked to a lower severity of depressive symptoms, suggesting that early intervention may alter the depressive symptom trajectory. Here, we suggest a complex interaction between psychotic and depressive symptoms, possibly indicating a biological antagonism. The association of depressive symptoms with disorganized and obsessive-compulsive features may reflect an adaptive psychological response, attempting to stabilize amidst the disintegration of schizophrenia. These insights support a more integrated approach to treatment, addressing both psychotic and depressive symptoms to improve patient outcomes.
Update on the Biological and Clinical Relevance of Mast Cells in Chronic Rhinosinusitis with Nasal Polyps
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder whose complex immunopathogenesis has yet to be fully elucidated. Endotype-2 CRSwNP is the most common form of disease where eosinophils are the main drivers of inflammation. Traditional treatments for CRSwNP have centered around intranasal or systemic corticosteroids and endoscopic sinus surgery (ESS). However, recent advancements in targeted therapies have introduced novel biological agents that specifically target key inflammatory mediators such as IL-4, IL-5, and IL-13. These biologics offer promising options for patients with CRSwNP, particularly those who do not respond adequately to conventional treatments. Nonetheless, some patients do not satisfactorily respond to these drugs because of an insufficient blockade of the inflammatory process. The mast cell (MC) is another important (and somehow neglected) actor in the pathogenesis of CRSwNP, and the latest clinical and translational evidence in this field has been reviewed in the present paper.
Mitral Valve Transcatheter Edge-to-Edge Repair (MV-TEER) in Patients with Secondary Mitral Regurgitation Improves Hemodynamics, Enhances Renal Function, and Optimizes Quality of Life in Patients with Advanced Renal Insufficiency
Secondary mitral regurgitation (MR) is a common valvular heart disease burdening the prognosis of patients with co-existing chronic heart failure. Transcatheter edge-to-edge mitral valve repair (MV-TEER) is a minimally invasive treatment option for high-risk patients. However, the effects of MV-TEER on expanded hemodynamics, tissue perfusion, and quality of life, particularly in patients with advanced renal failure, remain underexplored.
Efficacy of High-Definition Transcranial Alternating Current Stimulation (HD-tACS) at the M1 Hotspot Versus C3 Site in Modulating Corticospinal Tract Excitability
Previous studies have shown that beta-band transcranial alternating current stimulation (tACS) applied at the M1 hotspot can modulate corticospinal excitability. However, it remains controversial whether tACS can influence motor unit activities at the spinal cord level. This study aims to compare the efficacy of applying tACS over the hotspot versus the conventional C3 site on motor unit activities and subsequent behavioral changes. This study used a randomized crossover trial design, where fifteen healthy participants performed a paced ball-squeezing exercise while receiving high-definition tACS (HD-tACS) at 21 Hz and 2 mA for 20 min. HD-tACS targeted either the flexor digitorum superficialis (FDS) hotspot or the C3 site, with the order of stimulation randomized for each participant and a 1-week washout period between sessions. Motor unit activities were recorded from the FDS. HD-tACS intervention significantly reduced the variability of motor unit firing rates and increased force variability during isometric force production. The significant modulation effects were seen only when the intervention was applied at the hotspot, but not at the C3 site. Our findings demonstrate that HD-tACS significantly modulates motor unit activities and force variability. The results indicate that cortical-level entrainment by tACS can lead to the modulation of spinal motor neuron activities. Additionally, this study provides further evidence that the C3 site may not be the optimal target for tACS intervention for hand muscles, highlighting the need for personalized neuromodulation strategies.
Correction: Chen et al. Heteronemin Suppresses Lymphangiogenesis Through ARF-1 and MMP-9/VE-Cadherin/Vimentin. 2021, , 1109
[...].
Types of Injuries and the Severity of Shoulder Dysfunction Associated with Diabetes Mellitus in Patients with Functional Impairment: A Case-Control Study
Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients.
A Metabolomic Approach to Unexplained Syncope
This study aims to identify a metabolomic signature that facilitates the classification of syncope and the categorization of the unexplained syncope (US) to aid in its management. We compared a control group (CTRL, = 10) with a transient loss of consciousness (TLC) group divided into the OH group ( = 23) for orthostatic syncope, the NMS group ( = 26) for neuromediated syncope, the CS group ( = 9) for cardiological syncope, and the US group ( = 27) for US defined as syncope without a precise categorization after first- and second-level diagnostic approaches. The CTRL and the TLC groups significantly differed in metabolic profile. A new logistic regression model has been developed to predict how the US will be clustered. Using differences in lysophosphatidylcholine with 22 carbon atom (C22:0-LPC) levels, 96% of the US belongs to the NMS and 4% to the CS subgroup. Differences in glutamine and lysine (GLN/LYS) levels clustered 95% of the US in the NMS and 5% in the CS subgroup. We hypothesize a possible role of C22:0 LPC and GLN/LYS in re-classifying US and differentiating it from cardiological syncope.
Correction: Sharma et al. Modulation of Renal Injury by Variable Expression of Myo-Inositol Oxygenase (MIOX) via Perturbation in Metabolic Sensors. 2020, , 217
In the original publication [...].
Correction: Musumeci et al. Intranasal Administration of a TRAIL Neutralizing Monoclonal Antibody Adsorbed in PLGA Nanoparticles and NLC Nanosystems: An In Vivo Study on a Mouse Model of Alzheimer's Disease. 2022, , 985
Figure 5 in the original publication [...].