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18 pages, 2859 KB  
Review
Clinical Practice Recommendations for Non-Dermatologists on the Diagnostic Suspicion of GPP
by Antonella Di Cesare, Elia Rosi, Annalisa Cavallo, Serena Guiducci, Anna Lucia Marigliano, Simone Vanni and Francesca Prignano
J. Clin. Med. 2026, 15(15), 6087; https://doi.org/10.3390/jcm15156087 - 5 Aug 2026
Abstract
Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, chronic cutaneous inflammatory disease characterized by unpredictable, recurrent acute flares of painful sterile pustules on a widespread erythematous background. In addition to cutaneous manifestations, patients may experience fever, pruritus, pain, chills, and general malaise, [...] Read more.
Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, chronic cutaneous inflammatory disease characterized by unpredictable, recurrent acute flares of painful sterile pustules on a widespread erythematous background. In addition to cutaneous manifestations, patients may experience fever, pruritus, pain, chills, and general malaise, which may be further complicated by secondary infection, sepsis, and organ failure, thus requiring urgent medical treatment and, in some cases, hospitalization. Prompt therapeutic management of the acute phase is crucial for severe cases, and proactive treatment to prevent flares should always be considered. However, early recognition of acute flares can be challenging due to the low frequency of the disease, the rapid onset of flares, the lack of hematological biomarkers and the absence of standardized diagnostic criteria. Moreover, despite the approval of new targeted therapies, there are still several unmet needs, as these treatments are highly expensive, not always readily available, and may have limited efficacy in patients with advanced or complicated disease. For these reasons, multidisciplinary round-table discussions and shared diagnostic and therapeutic algorithms involving dermatologists, who are responsible for diagnosing and treating GPP, and other medical specialists are desirable to facilitate prompt referral to dermatologists for accurate diagnosis and appropriate treatment. We report the updated literature discussed during a multidisciplinary meeting with the aim of providing practice recommendations for clinicians involved in GPP management. Full article
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16 pages, 1348 KB  
Article
Traditional Mongolian Rhythmical Vibration Therapy for Low Back Pain: Acute Mechanisms and Three-Year Sustainability
by Molor Radnaabazar, Tserendagva Dalkh and Odontsetseg Ganbaatar
Healthcare 2026, 14(15), 2357; https://doi.org/10.3390/healthcare14152357 - 3 Aug 2026
Viewed by 61
Abstract
Background/Objectives: Traditional Mongolian Rhythmical Vibration Therapy (RVT) is a manual intervention utilizing low-frequency mechanical oscillations, yet its biomechanical effects lack objective quantification. The present study aimed to evaluate the impact of manual RVT on paraspinal muscle stiffness and its long-term sustainability on the [...] Read more.
Background/Objectives: Traditional Mongolian Rhythmical Vibration Therapy (RVT) is a manual intervention utilizing low-frequency mechanical oscillations, yet its biomechanical effects lack objective quantification. The present study aimed to evaluate the impact of manual RVT on paraspinal muscle stiffness and its long-term sustainability on the quality of life (QoL) in patients with chronic low back pain (LBP). Methods: To evaluate treatment mechanisms and long-term sustainability, this investigation utilized an acute comparative framework (n = 60) alongside a three-year longitudinal observational study design (n = 60) using consecutive convenience sampling. To assess biomechanical efficacy, paraspinal stiffness was measured via mytonometry, contrasting manual RVT against mechanical percussive vibration. Additionally, the long-term sustainability of outcomes was evaluated where clinical efficacy was quantified using the Roland-Morris Disability Questionnaire (RMQ) and the WHOQoL instrument, supported by a post-treatment metered walking regimen (Terrenkur). Within- and between-group changes were analyzed using paired and independent t-tests. Results: A Manual RVT yielded statistically significant and greater reduction in paraspinal muscle stiffness compared to mechanical vibration (p < 0.05). Immediate clinical outcomes revealed significant reductions in RMQ scores, which dropped from 13.33 ± 2.046 to 3. 40 ± 1.522 (p < 0.001, Cohen’s d = 4.20). At the three-year follow-up, participants maintained significantly high quality of life scores across physical, psychological, and social domains (p < 0.001, effect sizes d > 0.80). Conclusions: Manual RVT is associated with reduced paraspinal muscle stiffness in chronic LBP patients. The integration of this manual therapy with a Terrenkur maintenance regimen appears to support the maintenance of functional and quality of life improvements over a three-year period. However, given the observational design of the study, these outcomes must be interpreted cautiously, and randomized controlled trials are required to establish absolute therapeutic efficacy. Full article
(This article belongs to the Special Issue Advances in Manual Therapy: Diagnostics, Prevention and Treatment)
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74 pages, 7813 KB  
Review
Biopolymer-Based Hydrogels for Wound Healing: Advances in Cellulose, Chitosan, Alginate, and Hyaluronic Acid from Design to Clinical Translation
by Shery Jacob, Namitha Raichel Varkey, Sai H. S. Boddu, Jigar N. Shah, Rekha Rao and Anroop B. Nair
Pharmaceuticals 2026, 19(8), 1210; https://doi.org/10.3390/ph19081210 - 1 Aug 2026
Viewed by 217
Abstract
Wound healing is a multifaceted biological process comprising the phases of hemostasis, inflammation, proliferation, and remodeling, all of which require supportive microenvironment for optimal tissue regeneration. Biopolymer-based hydrogels, derived from materials such as cellulose and its derivatives, chitosan, alginate, and hyaluronic acid, have [...] Read more.
Wound healing is a multifaceted biological process comprising the phases of hemostasis, inflammation, proliferation, and remodeling, all of which require supportive microenvironment for optimal tissue regeneration. Biopolymer-based hydrogels, derived from materials such as cellulose and its derivatives, chitosan, alginate, and hyaluronic acid, have emerged as promising wound dressing materials due to their excellent biocompatibility, biodegradability, moisture-retention capacity, and potential to mimic the native extracellular matrix. The structural characteristics, wound healing functions, and underlying mechanisms of these biopolymers are critically examined and summarized in tabular form. The review further highlights the incorporation of natural and synthetic therapeutic agents, growth factors, stem-cell-derived products, and peptides into biopolymer matrices to enhance therapeutic efficacy. The examined research findings indicate significant increases in fluid intake, moisture retention, antibacterial activity, angiogenesis, collagen deposition, tissue regeneration, and wound healing rates. Translational difficulties, regulatory issues, clinical research, and new patent activity pertaining to advanced wound healing biomaterials are also covered in the review. Despite tremendous improvements, issues still exist in bulk manufacturing, long-term safety, reproducibility, mechanical stability, and clinical validation. Future innovations are anticipated to concentrate on smart, multipurpose, and customized hydrogel systems that can integrate drug delivery, biosensing, and regenerative capabilities while reacting dynamically to wound microenvironments. Overall, biopolymer-based hydrogels are a flexible, rapidly developing platform with significant promise to improve next-generation skin tissue engineering and change the treatment of both acute and chronic wounds. Full article
(This article belongs to the Section Pharmaceutical Technology)
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23 pages, 805 KB  
Review
Neuromodulation to Promote Recovery Following Traumatic Brain Injury: A Narrative Review of Current Pharmacologic and Non-Pharmacologic Approaches
by Cindy K. Wong, Nilsha Khurana, Raya T. Aliakbar and Roy A. Poblete
Brain Sci. 2026, 16(8), 813; https://doi.org/10.3390/brainsci16080813 - 30 Jul 2026
Viewed by 278
Abstract
Traumatic brain injury (TBI) is a leading cause of long-term neurological disability worldwide and is frequently associated with persistent impairments in consciousness, cognition, mood, and functional independence. Despite advances in acute neurocritical care, effective therapies that enhance neurological recovery remain limited. Neuromodulation has [...] Read more.
Traumatic brain injury (TBI) is a leading cause of long-term neurological disability worldwide and is frequently associated with persistent impairments in consciousness, cognition, mood, and functional independence. Despite advances in acute neurocritical care, effective therapies that enhance neurological recovery remain limited. Neuromodulation has emerged as a promising strategy to augment neuroplasticity and improve recovery through both pharmacologic and non-pharmacologic approaches. This narrative review summarizes current evidence supporting pharmacologic neuromodulatory therapies, including central nervous system stimulants (methylphenidate and modafinil), dopaminergic agents (amantadine and bromocriptine), acetylcholinesterase inhibitors (donepezil and rivastigmine), and selective serotonin reuptake inhibitors (sertraline and fluoxetine). Mechanisms of action, clinical efficacy, adverse effects, and practical considerations across the acute, subacute, and chronic phases of TBI recovery are discussed. Emerging non-pharmacologic neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation, are also reviewed. Although amantadine remains the only neuromodulator supported by moderate-quality guideline recommendations for accelerating recovery in disorders of consciousness, accumulating evidence suggests that several additional pharmacologic and non-pharmacologic neuromodulation interventions may improve attention, executive function, fatigue, mood, and rehabilitation participation in carefully selected patients. However, current evidence is limited by heterogeneous study populations, small sample sizes, inconsistent outcome measures, and a paucity of long-term randomized controlled trials. Future research should prioritize adequately powered comparative studies, standardized outcome measures, biomarker-guided patient selection, and multimodal treatment strategies to optimize neurological recovery following TBI. Full article
(This article belongs to the Special Issue Exploring Rehabilitation Strategies and Biomarkers for Brain Injury)
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11 pages, 204 KB  
Article
Cutaneous Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Cohort Study of Clinical Spectrum and Treatment Patterns
by Annunziata Raimondo, Annunziata Nigro, Mara Corbisieri, Valentina Giudice, Bianca Serio, Serena Lembo and Carmine Selleri
Life 2026, 16(8), 1255; https://doi.org/10.3390/life16081255 - 29 Jul 2026
Viewed by 160
Abstract
Cutaneous graft-versus-host disease (GVHD) is a common complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Despite established guidelines, discrepancies persist between clinical trial evidence and real-world practice, particularly for newer agents such as ruxolitinib. To characterize the phenotypic spectrum of cutaneous GVHD, evaluate [...] Read more.
Cutaneous graft-versus-host disease (GVHD) is a common complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Despite established guidelines, discrepancies persist between clinical trial evidence and real-world practice, particularly for newer agents such as ruxolitinib. To characterize the phenotypic spectrum of cutaneous GVHD, evaluate real-world treatment strategies—with a specific focus on systemic and topical ruxolitinib—and assess adherence to national and international guidelines, we conducted a retrospective observational study of patients undergoing allo-HSCT between 2015 and 2025 who were referred to a dedicated dermato-haematology clinic. Clinical, histological, and therapeutic data were collected. Cutaneous manifestations were classified according to National Institutes of Health (NIH) and Italian Group for Blood and Marrow Transplantation (GITMO) criteria. Of 62 transplanted patients, 44 (71%) developed GVHD, with the skin as the most frequently involved organ. Acute GVHD predominantly presented with maculopapular eruptions, whereas chronic GVHD showed heterogeneous phenotypes, including sclerotic variants. First-line management was largely guideline-concordant. Systemic ruxolitinib was administered to 3% of patients in the aGVHD group and 3% in the cGVHD group. Steroid-refractory and steroid-dependent status was not systematically recorded; therefore, treatment eligibility could not be reliably determined, and the observed frequencies should not be interpreted as evidence of underuse. Topical ruxolitinib was not used and remains investigational for cutaneous GVHD. Interpretation should also consider that the study period encompassed changes in regulatory approval, reimbursement, and access to targeted therapies. Structured multidisciplinary assessment may support the management of complex cutaneous GVHD, although its effects on treatment decisions and patient outcomes require prospective evaluation. Full article
(This article belongs to the Special Issue Pathogenesis, Biomarkers, and Treatments of Skin Diseases)
21 pages, 7957 KB  
Article
HSV-1 Infection Differentially Modulates NPY and VIP Neuropeptide Expression in the Mouse Brain and in Human Neuronal Cells
by Javier Carbone-Schellman, Nicolás Sales-Salinas, Rodrigo Reyes-Ramírez, Benjamín Rodríguez, Patricia Pereira-Sánchez, Gisella Vásquez-Canales, José A. Jara, Alfredo Molina-Berríos, Boris Rebolledo-Jaramillo, Alexis M. Kalergis, Pablo A. González and Luisa F. Duarte
Int. J. Mol. Sci. 2026, 27(15), 6735; https://doi.org/10.3390/ijms27156735 - 28 Jul 2026
Viewed by 260
Abstract
Neurotropic viruses can alter neuronal responses in the central nervous system (CNS), significantly affecting viral clearance and disease progression. Herpes simplex virus type 1 (HSV-1) brain infection may lead to life-threatening severe acute encephalitis in untreated patients and neurological sequelae in survivors despite [...] Read more.
Neurotropic viruses can alter neuronal responses in the central nervous system (CNS), significantly affecting viral clearance and disease progression. Herpes simplex virus type 1 (HSV-1) brain infection may lead to life-threatening severe acute encephalitis in untreated patients and neurological sequelae in survivors despite antiviral treatment. Notably, asymptomatic brain infection occurs in an important proportion of healthy individuals (>35%) and is associated with residual chronic neuroinflammatory responses that may lead to neurodegeneration. Therefore, understanding the molecular basis of these detrimental effects and finding and advancing new therapeutic strategies to manage HSV-1 brain infections are needed. Neuropeptides are pleiotropic neuroimmune mediators expressed throughout the CNS that modulate glial activation, cytokine production, and neuronal survival. However, their regulation during HSV-1 brain infections remains largely unexplored. Here, we sought to investigate the expression dynamics of two neuropeptides, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), in two mouse strains that model human traits of symptomatic and asymptomatic HSV-1 brain infections (BALB/c and C57BL/6, respectively), as well as in the human neuroblastoma cell line SH-SY5Y, to uncover potential differences that could help explain the susceptibility of some individuals to develop severe HSV-1 infection. Our findings provide evidence that HSV-1 brain infection modulates NPY and VIP mRNA expression in a neurovirulence- and host-susceptibility-dependent manner, which may be associated with disease severity and chronic damage, warranting further evaluation. Full article
(This article belongs to the Special Issue Molecular Mechanism and Therapeutic Strategy in Viral Infection)
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18 pages, 546 KB  
Review
Lithium in Bipolar Disorder: Renal Mechanisms, Nephrotoxicity Phenotypes, and a Shared-Care Pathway for Clinical Practice
by Nikolina Rijavec and Željka Večerić-Haler
Int. J. Mol. Sci. 2026, 27(15), 6730; https://doi.org/10.3390/ijms27156730 - 28 Jul 2026
Viewed by 221
Abstract
Lithium remains a cornerstone mood stabilizer for bipolar disorder, with strong evidence for relapse prevention and a unique association with reduced suicide risk. Its benefit is counterbalanced by renal adverse effects, ranging from impaired urinary concentrating capacity and nephrogenic diabetes insipidus (NDI) to [...] Read more.
Lithium remains a cornerstone mood stabilizer for bipolar disorder, with strong evidence for relapse prevention and a unique association with reduced suicide risk. Its benefit is counterbalanced by renal adverse effects, ranging from impaired urinary concentrating capacity and nephrogenic diabetes insipidus (NDI) to chronic tubulointerstitial nephropathy with progressive loss of glomerular filtration rate in a minority of long-term users. Mechanistically, lithium enters collecting duct principal cells via the epithelial sodium channel, disrupts vasopressin-regulated water handling by downregulating aquaporin-2, and can drive chronic interstitial injury. Risk is amplified by episodes of lithium intoxication, dehydration, interacting medications that reduce renal lithium clearance, longer treatment duration, and comorbid kidney disease. This review integrates psychiatric and nephrologic perspectives on lithium’s indications, mechanisms, renal phenotypes, and prevention strategies, and proposes a practical shared-care pathway for patients with bipolar disorder who develop polyuria, NDI, acute kidney injury, or chronic kidney disease during lithium therapy, emphasizing monitoring, targeted treatment of polyuria, mitigation of toxicity, and structured shared decision-making when renal function declines. Full article
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14 pages, 511 KB  
Article
The Pilonidal Sinus Disease-Specific Quality of Life Questionnaire (SQoL): Reliability, Validity, and Utilisation
by Edvinas Dainius, Monika Vaiciute, Edgaras Burzinskis, Audrius Parseliunas, Tadas Latkauskas, Violeta Simatoniene, Silvija Ilgunaityte, Donatas Venskutonis and Algimantas Tamelis
J. Clin. Med. 2026, 15(15), 5875; https://doi.org/10.3390/jcm15155875 - 27 Jul 2026
Viewed by 192
Abstract
Background: Pilonidal sinus disease is an inflammatory condition characterised by formations ranging from minor cysts to extensive sinus tracts in the natal cleft in the sacrococcygeal area. Due to its complex and unique symptoms, the condition may not be adequately captured by the [...] Read more.
Background: Pilonidal sinus disease is an inflammatory condition characterised by formations ranging from minor cysts to extensive sinus tracts in the natal cleft in the sacrococcygeal area. Due to its complex and unique symptoms, the condition may not be adequately captured by the generic quality of life (QoL) instruments. In this study, we evaluated a newly developed pilonidal sinus disease-specific quality of life (SQoL) questionnaire, valuating its validity and applicability for measuring postoperative outcomes of pilonidal sinus disease. Materials and Methods: The study involved developing a SQoL. A total of 116 adult patients with chronic and acute symptomatic disease at the Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS) were asked to complete both the SQoL and the SF-36v2 questionnaire. Key evaluation criteria for the SQoL questionnaire included internal consistency, measurement stability, as well as construct and discriminant validity. Results: 2 months after the procedure, 103 patients (response rate 88.79%) completed both questionnaires. Internal consistency was assessed 1 week after surgery, with the overall questionnaire achieving a Cronbach’s α coefficient of 0.919. The Spearman correlation coefficient for the total questionnaire score in the test–retest validation was 0.55 (CI 0.406–0.679), indicating a moderately significant correlation for all questions. Construct validity was evaluated by comparing the SQoL questionnaire with the results from various SF-36v2 domains 1 week after surgery. The highest inverse correlations were found between the corresponding domains of Physical Functioning and Role Physical Functioning (−0.770 and −0.600), with all correlations being statistically significant. Conclusions: A newly developed SQoL questionnaire has shown promise in assessing the impact of the disease and its treatment, particularly by addressing disease-specific symptoms. Standardising outcome measures can improve the reliability of meta-analyses and systematic reviews, which in turn helps to create more personalised care plans. The trial was registered in ClinicalTrials.gov with the identifier of NCT05982028. Full article
(This article belongs to the Special Issue Colorectal Surgery: Advances in Modern Clinical Management)
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21 pages, 3501 KB  
Article
Transferosomes Containing 20-Hydroxyecdysone for Psoriasis Treatment: Preparation, Characterization, and In Vitro and In Vivo Toxicity Assessment
by Pawel Bakun, Dariusz T. Mlynarczyk, Kacper Durowicz, Szymon Tomczak, Jolanta Dlugaszewska, Daniel Ziental, Robert Kleszcz, Aleksandra Majchrzak-Celińska, Ewelina Musielak, Mateusz de Mezer, Mikołaj Baranowski, Aneta Wozniak-Braszak, Emilia Cicha, Violetta Krajka-Kuzniak, Anna Jelinska, Tomasz Goslinski and Ludwika Piwowarczyk
Pharmaceuticals 2026, 19(8), 1157; https://doi.org/10.3390/ph19081157 - 25 Jul 2026
Viewed by 304
Abstract
Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products [...] Read more.
Background/Objectives: Psoriasis is a chronic, immune-mediated inflammatory skin disorder affecting millions of individuals worldwide. It remains a therapeutic challenge due to the limited skin penetration of many drugs, adverse systemic effects, and the need for long-term management. Transferosomal nanoformulations containing natural products were proposed as a potential therapeutic tool. Methods: Transferosomes containing 20-hydroxyecdysone and resveratrol were prepared using the thin-film hydration method followed by probe ultrasonication, generating several formulation variants differing in composition. The vesicles were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) to determine size, polydispersity index (PDI), and zeta potential. Furthermore, time-domain nuclear magnetic resonance (TD-NMR) relaxation measurements were employed to evaluate local molecular dynamics and membrane fluidity, providing deeper insights into the structural integrity and elasticity of the transferosomal systems. The stability of the nanoformulations was assessed for one month in water and phosphate-buffered saline (PBS). Viability was evaluated in vitro using the MTS assay on human epidermal keratinocyte (HEK) and psoriasis-patient derived human epidermal keratinocyte (PHEK) cell lines, alongside antimicrobial profiling against four representative human skin microbiome strains. Acute toxicity was further examined in vivo using the Danio rerio FET test. Results: The formulations demonstrated high physicochemical stability over the tested period, maintained desirable particle sizes within 100–200 nm, and showed no cytotoxicity toward skin-associated bacteria or in the zebrafish model. Conclusions: The developed nanoformulations present suitable properties in terms of safety and stability and can be considered for potential use in psoriasis treatment. Full article
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24 pages, 1555 KB  
Review
Blood–Brain Barrier Changes and Related Microvascular Outcomes in Long-COVID: A Comprehensive Review
by Marcella Chagas-Sena, Wei Ling Lau, Thomas Edward Lane, Paola Cristina Resende and Ane Claudia Fernandes Nunes
Life 2026, 16(8), 1227; https://doi.org/10.3390/life16081227 - 24 Jul 2026
Viewed by 1399
Abstract
Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the [...] Read more.
Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the blood–brain barrier (BBB) are central mechanisms for acute and chronic ischemic and hemorrhagic cerebral events. Understanding these mechanisms is vital to reducing their impact on population health, whether through treatment or prevention of adverse outcomes. The objective of this study is to perform a review of the scientific literature on the post-infection effects of SARS-CoV-2 affecting the cerebral endothelium and the BBB, correlating them with potential clinical outcomes. Material and Methods: Analysis of studies extracted from the PubMed database using the following terms: Long-COVID “AND” SARS-CoV-2 “AND” blood–brain barrier. Inclusion criteria: keywords, publications related to the topic, and primary studies published after peer review. Exclusion criteria: preprint studies, publication outside of the timeframe 2020–2025, study design not compatible with this research, and full text not available. Results: An initial 121 studies were identified, of which 105 were excluded due to not meeting all inclusion criteria and 6 studies were inaccessible due to not being in the English language and full-text access limitations. Fifteen articles were included in the analysis, for topics as expression of viral receptors in the endothelium, markers of their activation, cerebral microvascular injury and coagulopathies. To clarify the pathogenic cascade, the evidence was stratified by biological model where in vitro evidence demonstrates that the Spike protein induces direct endothelial toxicity and platelet aggregation, establishing the primary molecular insult. Animal models confirm the translation of this insult into structural degradation of the BBB and pericyte loss. Clinically, infection-phase findings, characterized by multifocal microthrombosis and permeability spikes, act as the determining event that predisposes to the persistent neuroinflammatory environment. Biomarkers of BBB disruption and neuronal damage were consistently reported, with persistence of BBB dysfunction modifying risk stratification and rehabilitation efforts. Reported cases of Long-COVID demonstrated normalization of BBB markers without correlation with long-term symptoms, suggesting that other mechanisms are involved in Long-COVID. Conclusion: Cerebral endotheliopathies and BBB dysfunction in patients with COVID-19 continue to impact the health of the population. The scientific literature indicates that SARS-CoV-2 induces cerebral endothelial injury, BBB disruption, and an increased risk of vascular events related to endotheliopathy, inflammation, and hypercoagulability. Understanding the impact of COVID-19 pathology on the population and developing prospective studies is essential to quantify the prevalence and mechanisms of brain injury. The identification of molecular targets and infection pathways are promising toward defining both preventive and therapeutic strategies to improve outcomes in the Long-COVID population. Full article
(This article belongs to the Special Issue Outlook for Cerebrovascular Damage Research)
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19 pages, 3012 KB  
Article
Effect of the Proteasome Inhibitor, Bortezomib, on Histone Modifications in Human Leukemic Cell Lines
by Hedieh Sattarifard, Marvellous Oyeyode, Dhanvi Prajapati, Angela Duaqui, Gurlovleen Kaur, Ishdeep Muker, Wenxia Luo, Ted M. Lakowski and James R. Davie
Int. J. Mol. Sci. 2026, 27(15), 6597; https://doi.org/10.3390/ijms27156597 - 24 Jul 2026
Viewed by 332
Abstract
Histone-modifying enzymes and histone post-translational modifications (PTMs) play key roles in the organization (euchromatin versus heterochromatin) and function (active versus silenced genes) of chromatin. The abundance and activity of these enzymes, along with their associated histone PTMs, are often altered in cancer cells, [...] Read more.
Histone-modifying enzymes and histone post-translational modifications (PTMs) play key roles in the organization (euchromatin versus heterochromatin) and function (active versus silenced genes) of chromatin. The abundance and activity of these enzymes, along with their associated histone PTMs, are often altered in cancer cells, leading to deregulated gene expression. The expression of the KMT2A-MLLT3 protein, resulting from a chromosomal translocation in mixed-lineage leukemia (MLL), a subtype of acute myeloid leukemia, augments transcription elongation, promoting the expression of HOXA9 and MEIS1, genes that play critical roles in MLL development. Bortezomib, a proteasome inhibitor, has been effective at treating various cancers. In this study, we compared the impact of bortezomib on histone PTMs in the MLL cell line MOLM-13 and the chronic myeloid leukemic (CML) cell line K562. We report that MOLM-13 had a greater level of histone H2B monoubiquitinated at lysine 120 (H2BK120ub) and histone H3 dimethylated at lysine 79 (H3K79me2) (modifications involved in elongation) and similar levels of histone H2A monoubiquitinated at lysine 119 (H2AK119ub). Bortezomib treatment resulted in significant reductions in H2BK120ub and H2AK119ub levels, as well as in transcript levels of genes involved in MLL development. Full article
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20 pages, 436 KB  
Article
Real-World Use of Cefiderocol for Multidrug-Resistant Gram-Negative Infections in Critically Ill ICU Patients: A Single-Center Case Series
by Stelian Adrian Ritiu, Adelina Baloi, Marius Păpurică, Dorel Sandesc, Daiana Toma, Claudiu Rafael Bârsac, Sonia Elena Popovici, Madalina Butaș, Ana-Maria-Ionela Botoaca and Ovidiu Bedreag
Pathogens 2026, 15(8), 786; https://doi.org/10.3390/pathogens15080786 - 24 Jul 2026
Viewed by 222
Abstract
Background/Objectives: Carbapenem-resistant Gram-negative (CR-GN) infections are associated with high mortality in intensive care units (ICUs), with limited therapeutic options. We aimed to evaluate microbiological and clinical outcomes associated with cefiderocol in critically ill patients with multidrug-resistant (MDR) Gram-negative infections. Methods: This retrospective, single-center [...] Read more.
Background/Objectives: Carbapenem-resistant Gram-negative (CR-GN) infections are associated with high mortality in intensive care units (ICUs), with limited therapeutic options. We aimed to evaluate microbiological and clinical outcomes associated with cefiderocol in critically ill patients with multidrug-resistant (MDR) Gram-negative infections. Methods: This retrospective, single-center case series included 25 critically ill patients with carbapenem-resistant or multidrug-resistant Gram-negative infections treated with cefiderocol between May 2024 and October 2025 in a mixed ICU of a tertiary hospital in Romania. Microbiological cure was defined as eradication of the designated target pathogen at the end of therapy. Clinical evolution was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, as well as inflammatory biomarkers including white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Results: Klebsiella pneumoniae was the predominant pathogen, identified in 23 of 25 patients (92%), followed by Acinetobacter baumannii (11/25, 44%) and Pseudomonas aeruginosa (6/25, 24%). As multiple pathogens were co-isolated in 16 patients (64%), percentages exceed 100% and are reported as proportions of patients rather than of total isolates. Microbiological cure was achieved in 68% of patients. Mortality was markedly higher in patients without microbiological eradication (88% vs. 35%). Higher baseline APACHE II (HR 1.18, 95% CI 1.02–1.37) and SOFA scores (HR 1.33, 95% CI 1.07–1.65) were associated with increased mortality. Early initiation of cefiderocol (≤10 days from ICU admission) was associated with improved microbiological and clinical outcomes compared to delayed treatment. Reductions in severity scores and inflammatory markers, including C-reactive protein (CRP) and procalcitonin (PCT), were observed during therapy. Pathogen type and combination therapy were not clearly associated with outcomes in this cohort. Conclusions: Cefiderocol was observed in association with clinically relevant rates of microbiological eradication and improvements in clinical parameters in critically ill patients with MDR Gram-negative infections. Outcomes appeared to be primarily determined by baseline disease severity, while earlier initiation of therapy was associated with more favourable microbiological and clinical outcomes, although causality cannot be established given the observational design and absence of a comparator group. These findings are hypothesis-generating and supportive of a potential role for cefiderocol as a salvage option in high-risk ICU populations, pending validation in larger, prospective, controlled studies. Full article
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16 pages, 3248 KB  
Article
Discovery of a Novel 4,5-Dihydro-1H-pyrazole-1-carbothioamide Derivative with Cytotoxic, Apoptotic, and ABL1 Inhibitory Activities Against Chronic Myeloid Leukemia
by Ayben Erkan, Ayca Irgit Calayir, Halilibrahim Ciftci and Belgin Sever
Biomedicines 2026, 14(7), 1651; https://doi.org/10.3390/biomedicines14071651 - 22 Jul 2026
Viewed by 360
Abstract
Background/Objectives: Chronic myeloid leukemia (CML) is a hematological malignancy driven by the constitutively active BCR-ABL1 fusion protein. Although current ABL1 tyrosine kinase inhibitors (TKIs) have improved CML management, resistance remains a major challenge, highlighting the need for novel therapeutic strategies. Methods: [...] Read more.
Background/Objectives: Chronic myeloid leukemia (CML) is a hematological malignancy driven by the constitutively active BCR-ABL1 fusion protein. Although current ABL1 tyrosine kinase inhibitors (TKIs) have improved CML management, resistance remains a major challenge, highlighting the need for novel therapeutic strategies. Methods: A chalcone derivative containing naphthalene and toluene moieties (A) was synthesized from 2-acetonaphthone and p-tolualdehyde and subsequently converted into a novel 4,5-dihydro-1H-pyrazole-1-carbothioamide derivative (B) through reaction with thiosemicarbazide. The cytotoxicity of compounds A and B against K562 CML cells was evaluated using the MTT assay. The active compound was further investigated for cytotoxic selectivity using HL-60 acute myeloid leukemia (AML) cells and healthy PBMCs. Apoptotic effects in K562 cells were analyzed using Annexin V/ethidium homodimer staining, whereas ABL1 inhibitory activity was determined using the ADP-Glo kinase assay. The potential interaction between the active compound and ABL1 was assessed by molecular docking analysis. Results: Compound B displayed potent cytotoxic activity against K562 cells with an IC50 value of 6.92 ± 1.14 µM and demonstrated selectivity toward leukemic cells over PBMCs (SI = 5.4). Treatment with compound B markedly induced apoptosis in K562 cells. In addition, compound B inhibited ABL1 activity in a concentration-dependent manner. Molecular docking studies revealed a favorable binding orientation within the ATP-binding pocket of ABL1. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) analysis predicted favorable pharmacokinetic properties for compound B. Conclusions: These findings demonstrate that compound B possesses cytotoxic, pro-apoptotic, and ABL1 inhibitory activities against CML cells and may serve as a promising lead structure for the development of novel therapeutic agents targeting CML. Full article
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15 pages, 689 KB  
Article
Investigation of the Anti-Toxoplasma gondii Potential of Loratadine
by Stephanie Ortega Alves, Ingrid de Oliveira Dias, Gabriel Candido Moura, Samuel Cota Teixeira and Juliana Quero Reimão
Pathogens 2026, 15(7), 773; https://doi.org/10.3390/pathogens15070773 - 22 Jul 2026
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Abstract
Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective [...] Read more.
Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through β-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development. Full article
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12 pages, 242 KB  
Article
Medication Patterns as a Lens on Health Needs Among Migrant Agricultural Workers in Informal Settlements in Apulia: A Descriptive Outreach Study
by Cesare De Virgilio Suglia, Renato Laforgia, Marcella Schiavone, Anna Belfiore, Giacomo Guido, Rosa Buonamassa, Alba Cuxart-Graell, Martina Di Noto, Valeria Mele, Emanuele Costanza, Venilia Cocco, Alexandre Meduri, Lucia Raho, Nicole Laforgia, Roberta Iatta, Giovanni Putoto and Francesco Di Gennaro
Infect. Dis. Rep. 2026, 18(4), 76; https://doi.org/10.3390/idr18040076 - 21 Jul 2026
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Abstract
Background: Migrant agricultural workers in Italy often experience social and health vulnerabilities, including unstable housing and limited access to primary care. In Southern Italy, many live in informal settlements and seek care through outreach services. This study describes patterns of pharmacological treatment in [...] Read more.
Background: Migrant agricultural workers in Italy often experience social and health vulnerabilities, including unstable housing and limited access to primary care. In Southern Italy, many live in informal settlements and seek care through outreach services. This study describes patterns of pharmacological treatment in this population and examines how they relate to the clinical conditions managed in mobile clinics. Methods: We analyzed routinely collected data from 2928 unique patients (8547 clinical encounters; 8965 treatment occurrences) managed by Doctors with Africa CUAMM mobile clinics in 12 informal settlements in Apulia, Italy, between 2017 and 2026. Diagnoses were grouped into clinical categories, and pharmacological treatments were classified by therapeutic class. We conducted a descriptive analysis of the distribution of diagnostic categories and associated treatments. Results: The population was predominantly male (96.5%), young (81% <45 years), and largely excluded from regular primary care (93.5% without a General Practitioner). Musculoskeletal disorders and fatigue were the leading diagnostic category (34.0%), followed by gastrointestinal (13.5%) and respiratory conditions (13.0%). Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics were the most frequently recorded treatments (32.6% of treatment occurrences). Among musculoskeletal presentations, NSAIDs were used in 76% of cases. Gastroprotective agents were documented in 52% of encounters with gastrointestinal symptoms. Among cardiovascular presentations, 87.7% of treatment occurrences involved chronic management with antihypertensives or beta-blockers. Conclusions: In this outreach setting, medication use provides a descriptive picture of common health problems and treatment responses among migrant agricultural workers living in informal settlements. The prominent use of symptomatic pharmacological relief, particularly NSAIDs in musculoskeletal conditions, suggests that care is often focused on managing pain and acute complaints in a population facing barriers to continuous primary care. These findings support the need for stronger inclusion of migrant workers in the National Health Service and for policies that address underlying social and structural determinants of health. Full article
(This article belongs to the Special Issue Infections in Vulnerable Populations)
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