Search Results (3,638)

Background/Objectives: This literature review aims to provide guidance on the treatment of recurrent aphthous stomatitis (RAS) based on studies published over the past 10 years. Methods: This study included randomized clinical trials involving human patients from 2013 and 2023, published in any language. The trials examined both pharmacological and non-pharmacological treatments for aphthous lesions, mainly focusing on the adult population, with pain management as the primary outcome. The research was conducted using PubMed, EMBASE, and CINHAL databases. Results: Most of the 45 analyzed studies focused on non-pharmacological therapies, which led to positive results with minimal adverse effects or contraindications, even when compared to cortisone-based treatments. Laser therapy also showed excellent results, particularly in the immediate post-treatment period. Non-pharmacological therapies appeared to offer the best risk–benefit ratio for patients suffering from RAS. Conclusions: Treatment should be individualized based on the patient’s specific form of RAS, and laser therapy can be used either as a standalone treatment or as an adjunct to other treatments considered in the review. Full article

Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time. Full article

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor, with fewer than 5% of patients surviving five years after diagnosis. The introduction of immune checkpoint inhibitors (ICIs), followed by chimeric antigen receptor (CAR) T-cell therapy, marked major advancements in oncology. Despite demonstrating efficacy in other blood and solid cancers, these therapies have yielded limited success in clinical trials for both newly diagnosed and recurrent GBM. A deeper understanding of GBM’s resistance to immunotherapy is essential for enhancing treatment responses and translating results seen in other cancer models. Objectives: In this review, we examine clinical trial outcomes involving ICIs and CAR-T for GBM patients and explore the evasive mechanisms of GBM and the tumor microenvironment. Findings and Discussion: Multiple clinical trials investigating ICIs in GBM have shown poor outcomes, with no significant improvement in progression-free survival (PFS) or overall survival (OS). Results from smaller case studies with CAR-T therapy have warranted further investigation. However, no large-scale trials or robust studies have yet established these immunotherapeutic approaches as definitive treatment strategies. Future research should shift focus from addressing the scarcity of functional T cells to exploiting the abundant myeloid-derived cells within the tumor microenvironment. Conclusions: Translating these therapies into effective treatments for glioblastoma in humans remains a significant challenge. The highly immunosuppressive nature of GBM and its tumor microenvironment continue to hinder the success of these innovative immunotherapeutic approaches. Targeting the myeloid-derived compartment may lead to more robust and sustained immune responses. Full article

Due to a continuous increase in life expectancy and the progress made in specialized healthcare, the incidence of Alzheimer’s disease (AD) has dramatically increased to the point that it has become one of the main challenges of contemporary medicine. Despite a huge scientific and clinical effort, current treatments manage just a temporary alleviation of symptomatology but offer no cure. Modern trials involving cell transplantation in experimental animals require the involvement of neurosurgeons in the treatment protocol. CSF shunting, intraventricular infusions, or DBS for symptoms relief have been an integral part of the therapeutic arsenal from the very beginning. The development of stereotactic surgery has facilitated the experimental potential of cell transplantation in the hippocampus for Alzheimer’s disease. We conducted a narrative review of the literature in the top three medical databases (PubMed, Science Direct, and Google Scholar) using the keywords “Alzheimer’s disease”, “hippocampus”, and “transplant”. After eliminating duplicates, 241 papers were selected and screened by title and abstract. Two reviewers independently analyzed the 88 papers and chose 32 experiments that involved stereotactic hippocampal transplantation of cells in experimental animals with AD. The stereotactic transplantation of cells such as mesenchymal stem cells (MSCs), neuronal stem cells (NSCs), induced pluripotent cells (iPSCs), astrocytes, and derivates from stem cells was analyzed. The experiments used either a chemically induced or transgenic AD model and observed the impact of the stereotactic transplantation with behavioral testing, MRS spectroscopy, and biochemical analysis. The stereotaxic method delivers minimal invasive treatment option by cell transplantation at the hippocampus. The results showed that amyloid deposits were lower after transplantation, showing a positive impact. Other impactful results involve proliferation of neurogenesis, downregulation of anti-inflammatory response, and increased neuronal plasticity. The increased precision with which the stereotaxic method manages to target deep structures of the brain and the results of the reviewed papers could represent an argument for future human trials. More studies are needed to confirm the viability of the transplanted cells and the long-term effects. Full article

Background: Colon cancer is known as one of the most prevalent malignancies in the world. This well-known pathology requires accurate lymph node dissection to achieve effective staging and improved treatment outcomes. Indocyanine green fluorescence imaging has been used as a new technique for enhancing lymph node visualization during surgical intervention. The high rates of local recurrence in colon cancer patients require innovative methods to improve lymphatic mapping and lymph node dissection. This review evaluates the clinical utility and efficacy of ICG imaging in enhancing lymph node accuracy in colon cancer surgery. Materials and methods: A systematic search was conducted in October 2024 (last day of consulting the database was 16 November) across Web of Science, Scopus, and PubMed to identify studies published from 2020 onwards focusing on the use of indocyanine green in colon cancer surgeries. The search terms used were “indocyanine green”, “ICG”, “fluorescent imaging”, “near-infrared imaging”, “colon cancer”, “colorectal cancer”, “colon carcinoma”,” colon neoplasms”, “surgery”, “surgical procedure”, “surgical resection”, surgical precision”. The search followed PRISMA guidelines. The records underwent a two-phase independent screening process conducted by the authors, first based on the title and abstract, followed by full record evaluation. Articles were excluded following certain exclusion criteria: non-human studies; restricted access publications; other publication type than article (review, meta-analysis, questionnaire-based study, case report, etc.), studies focusing on other diseases or studies that focused on the surgical treatment of metastasis from colon cancer; foreign language (non-English); no data of interest for the current review; studies that focused on rectal cancer and that grouped rectal and colon cancer. Data extraction involved both quantitative and qualitative data, such as detection rates, sensitivity, specificity, and other surgical outcomes. Risk of bias was assessed using ROBINS-I, J Joanna Briggs Institute (JBI) Critical Appraisal Checklist, and the Newcastle–Ottawa Scale, depending on study type. The study was not preregistered in PROSPERO. However, to ensure methodological rigor and transparency, it was retrospectively registered in Open Science Framework (OSF). Results: From the 3300 records initially identified, 9 studies were included in this review. Detection rates varied from 55% to 100%, with the highest rate reported in robot-assisted surgeries. The studies showed an improved lymph node detection and lymphatic flow accuracy using ICG fluorescence. Discussion: ICG fluorescence demonstrated substantial benefits, improving staging accuracy and potentially reducing recurrence rates by guiding the lymphadenectomy. The variability observed in detection rates is largely attributed to differences in ICG administration, cancer stage, and surgical approaches. Conclusions: ICG-guided surgery for colon cancer represents a promising advancement, enhancing lymph node detection and staging accuracy. Large-scale randomized trials are essential to establish standardized protocols and validate the efficacy in improving surgical outcomes. Full article

Xenobiotics, including drugs, undergo metabolism to facilitate detoxification and excretion. Predicting a compound’s metabolic fate before clinical trials is crucial for efficacy and safety. The existing methods rely on in vitro systems and in vivo animal testing. In vitro systems do not replicate the complexity of in vivo systems, and differences in biotransformation pathways between humans and nonclinical species may occur; thus, accurate predictions of human-specific drug metabolism are not always achieved. The aim of this study was to evaluate whether a chimeric mouse with a humanized liver, specifically the PXB-mouse, can mimic human metabolic profiles. PXB-mice have livers engrafted with up to 95% human hepatocytes. The biotransformation of 12 different small-molecule drugs were evaluated in PXB-mice (through analysis of blood and urine) and compared with the metabolism by hepatocytes from humans and mice and, when available, literature reports on human in vivo metabolism. The detected metabolites included major Phase I and II transitions, such as hydroxylation, and N- and O-dealkylation and glucuronidation. The metabolic patterns of the PXB-mice closely matched human in vivo data. It is also worth noting that the human hepatocytes formed most of the circulating metabolites, indicating that hepatocytes provide reliable predictions of human metabolic pathways. Thus, for drugs with human biotransformation pathways that are not observed in nonclinical species, the PXB-mouse model can be valuable in predicting human-specific metabolism. Full article

Objective: To investigate the preclinical efficacy and identify predictive biomarkers of polo-like kinase 1 (PLK1) inhibitors in small cell lung cancer (SCLC) models. Methods: We tested the cytotoxicity of selective PLK1 inhibitors (rigosertib, volasertib, and onvansertib) in a panel of SCLC cell lines. We confirmed the therapeutic efficacy of subcutaneous xenografts of representative cell lines and in four patient-derived xenograft models generated from patients with platinum-sensitive and platinum-resistant SCLC. We employed an integrated analysis of genomic and transcriptomic sequencing data to identify potential biomarkers of the activity and mechanisms of resistance in laboratory-derived resistance models. Results: Volasertib, rigosertib, and onvansertib showed strong in vitro cytotoxicity at nanomolar concentrations in human SCLC cell lines. Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. There was an association between YAP1 expression and disruptive or inactivation TP53 gene mutations, with greater efficacy of PLK1 inhibitors. Comparison of lab-derived onvansertib-resistant H526 cells to parental cells revealed differential gene expression with upregulation of NAP1L3, CYP7B1, AKAP7, and FOXG1 and downregulation of RPS4Y1, KDM5D, USP9Y, and EIF1AY highlighting the potential mechanisms of resistance in the clinical setting. Conclusions: We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965). Full article

Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region’s highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity. Methods: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides. Results: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at ¹⁶⁹K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site (¹⁷⁹LDV/I¹⁸¹) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions. Conclusions: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa. Full article

Background: Alveolar bone reconstruction with recombinant protein has several advantages, including less surgical timing, and reduced infection. This systematic review aims to assess the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a treatment modality for children with cleft lip and palate compared to the conventional iliac crest bone grafting approach. Methods: For current systematic review and meta-analysis, five electronic databases, namely, MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Web of Science, and ScienceDirect, were searched. The primary outcome measured in this review was bone volume and height after alveolar bone reconstruction surgery. The Risk of Bias Tool 2 assessed the risk of bias for randomized control trials and the Risk of Bias tool for non-randomized trials of interventions for non-randomized studies. By evaluating pooled meta-analysis, the mean difference was calculated. GRADE uncertainty of evidence was performed to assess the certainty of the results. Results: Of 230 identified studies, 6 randomized and 2 non-randomized studies were included in the current review. The average bone volume was higher among the rhBMP-2 group at 61.11% ± 24.6% than the iliac crest group at 59.12% ±18.59%. The calculated mean bone height was higher in the iliac crest group at 78.65% ± 14.38% than in the rhBMP-2 group at 67.5% ± 5.45%. The risk of bias reported in the studies was low to moderate. The result of the meta-analysis supported using rhBMP-2 in alveolar bone reconstruction; however, no significant association was found (mean difference: −1.24; confidence interval: −4.14 to 1.67). Conclusion: The calculated meta-analysis reported no significant difference, and the quality of evidence measured was also moderate. Hence, more clinical trials are required to support using rhBMP-2 as an alternative to traditional techniques for treating cleft lip and palate. Full article

Introduction: Traumatic brain injury (TBI) in pediatric population is responsible for significant mortality and morbidity, particularly among children aged 0–4 and young adults aged 15–24. The developing brain’s unique characteristics may increase vulnerability to injuries, potentially leading to long-term cognitive and motor deficits. Current therapeutic options for neuronal regeneration post-TBI are limited, although neurotrophins, especially nerve growth factor (NGF), show promise in enhancing recovery. NGF can mitigate excitotoxicity and promote neuroprotection, particularly by intranasal administration, which is attractive because of its non-invasive nature. Case Presentation: A three-year-old boy suffered from severe TBI due to a car accident, leading to multiple complications, including a basilar skull fracture and cerebral venous sinus thrombosis. Initial assessments revealed significant neurological impairments. After intensive care and rehabilitation, the child exhibited gradual improvements in consciousness and motor functions but continued to face challenges, particularly with left-sided hemiparesis. Nine months post-injury, he began intranasal administration of human-recombinant NGF (hr-NGF) as part of a clinical trial. Discussion: Following hr-NGF treatment, the child demonstrated notable advancements in motor function, achieving independent standing and walking. Cognitive assessments indicated improvements in various domains, including verbal comprehension and executive functioning. EEG results showed reduced epileptiform activity. These findings suggest that hr-NGF may facilitate recovery in pediatric TBI cases by enhancing both motor and cognitive outcomes. Conclusions: This case highlights the potential role of intranasal hr-NGF administration as a therapeutic strategy for improving neurological recovery in children with severe TBI. The positive clinical outcomes support further exploration of NGF as a viable treatment option to mitigate long-term sequelae associated with pediatric brain injuries. Full article

Background: Pharmacokinetic drug–drug interactions (DDIs) can be caused by the effect of a pharmaceutical compound on the activity of one or more subtypes of the Cytochrome P450 (CYP) family, UDP-glucuronosyltransferases (UGTs), and/or transporters. As the number of therapeutic areas with polypharmacy has increased, interest has grown in assessing the risk of DDIs during the early phases of drug development. Various lines of research have led to improved mathematical models to predict DDIs, culminating in the Food and Drug Administration’s (FDA) guidelines on evaluating pharmacokinetic DDI risks. However, the recommended static models are highly conservative and often result in false positive predictions. The current research aims to improve the workflow for assessing CYP-mediated DDI risk using Boehringer Ingelheim (BI) proprietary compounds. Methods: The Drug–drug Interaction Risk Calculator (PharmaPendium) was used to evaluate the mechanistic static model, and predictions were correlated with human pharmacokinetic studies from Phase I clinical trials. Results: The results demonstrated that the FDA formula performed well in predicting DDIs for BI proprietary compounds. Furthermore, the integration of either human renal excretion or preclinical species total excretion data into the mechanistic static model enhanced the predictive performance for candidate drugs as victims in DDIs. Conclusions: The basic static models (BSMs) for drug interactions should be used in early drug discovery to “rule out” DDI risks because of the minimal inputs required and the low rate of false negative predictions. Mechanistic static models (MSMs) can then be implemented for compounds that require additional evaluation. Full article

Porcine endogenous retrovirus C (PERV-C) is a gammaretrovirus present in the genome of many, but not all, pigs. It is an ecotropic virus, able to infect only pig cells. In contrast, PERV-A and PERV-B, which are present in all pigs, can infect cells of multiple host species, including humans, thereby posing a risk for xenotransplantation when pigs are used as donor animals. Notably, PERV-C can recombine with PERV-A to produce PERV-A/C recombinants that can infect human cells and replicate to higher titers compared to the paternal PERV-A. The objective of this study is to evaluate the reliability of both existing and newly developed polymerase chain reactions (PCR) methods for detecting PERV-C, with the aim of selecting PERV-C-free pigs to be used for xenotransplantation. To detect PERV-C by PCR, specific primers targeting the region of the envelope protein gene, which differs from that of PERV-A and PERV-B due to its unique receptor binding site, must be employed. In this study, new PCR assays were developed to detect PERV-C and a total of ten PCR assays and one real-time PCR assay were evaluated for their reliability in detecting PERV-C. These assays were used to screen indigenous Greek black pigs, Auckland Island pigs, and German slaughterhouse pigs. Two of the PCR assays consistently yielded reliable results, whereas the other PCRs and the real-time PCR gave false positive results. Using the reliable assays, it was shown that one out of four indigenous Greek black pigs (using the same method in a previous publication 11 of 21 pigs were found PERV-C-negative), one out of ten German slaughterhouse pigs, the pig kidney cell line PK15, and all the Auckland Island pigs were PERV-C-negative. The reliable PCR assays will enable the screening of PERV-C-negative donor pigs to be used in xenotransplantation. Most importantly, all the Auckland Island pigs that were genetically modified in Germany for use in clinical trials were PERV-C-negative. Full article

Background/Objectives: The effects of sweetened and unsweetened high β-glucan whole grain barley on postprandial blood glucose response in normoglycemic human subjects were evaluated in a randomized, controlled, crossover clinical trial. Methods: Sixteen healthy, over-night fasted participants were studied on four or eight separate occasions. Participants consumed an unsweetened preload condition (n = 16): white glutinous rice (WR; 0 g β-glucan), low β-glucan barley (LB; ~4 g), medium β-glucan barley (MB; ~5 g), or high β-glucan barley (HB; ~6 g); or a sweetened condition with high fructose corn syrup (HFCS; n = 8): WR + 50 g HFCS, LB + 50 g HFCS, MB + 50 g HFCS, or HB + 50 g HFCS. After consuming the preload as a breakfast food, participants self-administered blood glucose tests every 15 min for four hours. Results: In both sweetened and unsweetened conditions, higher β-glucan content was associated with lower blood glucose peak response and incremental area under the curve estimates (iAUC). In comparison to the unsweetened conditions, the sweetened conditions resulted in less prominent decreases in mean blood glucose response and iAUC blood glucose as β-glucan content increased. Conclusions: By attenuating postprandial glycemic response, high β-glucan whole grain barley foods could play a role in helping to control blood glucose. Full article

Background/Objectives: The need for innovative cancer treatments has brought immunotherapies to the forefront as a promising approach, with therapeutic vaccines demonstrating the potential to mobilize immune cells to eliminate tumor cells. However, challenges such as genetic variability among patients, immune evasion mechanisms, and disease relapse contribute to the complexity of achieving an ideal therapy, especially for hematological cancers. This review systematically identifies and analyzes recent studies focused on the development of therapeutic immunotherapy vaccines, examining critical aspects such as development stages, key assays for therapeutic validation, treatment outcomes, and study limitations. Methods: A scoping review was conducted following the PRISMA extension guidelines (PRISMA-ScR). Literature searches were conducted across Scopus, PubMed, Web of Science, and Science Direct databases using keywords including “immunotherapy”, “vaccines”, “immunization”, “hematological malignancies”, “blood cancer”, “hematopoietic neoplasms”, and “leukemia”. Results: A total of 56 articles published from 2013 to 2024 were included in the analysis. The majority of studies are in the preclinical stage, with some advancing to phase 1 and phase 2 clinical trials. Acute myeloid leukemia emerged as the most frequently studied malignancy. While first- and second-generation vaccines dominate the field, innovative approaches, such as dendritic-cell-based vaccines and mRNA vaccines, are gaining prominence. Notably, preclinical models often demonstrate superior outcomes compared to clinical trials, as results observed in animal models are not fully replicated in human studies. Conclusions: Despite challenges related to disease progression and patient loss, the studies reviewed highlight significant advancements in patient prognosis, emphasizing the potential of novel therapeutic vaccines as an effective alternative for the treatment of hematological cancers. Full article

Facial thread lifting with absorbable threads such as poly(L-lactide-co-ε-caprolactone) (P(LA/CL)) has been explored in an animal model. This experimental study utilized P(LA/CL)-HA-micro threads enhanced with hyaluronic acid microencapsulation via NAMICA technology in five four-month-old female pigs. The effects were compared to those of P(LA/CL)-HA threads over a six-month period through histological analysis. The results indicated improvements in skin remodeling, with P(LA/CL)-HA-micro threads enabling controlled and prolonged release of hyaluronic acid, leading to sustained improvements in tissue structure. These findings suggest that microencapsulated threads could enhance therapeutic outcomes; however, these results are preliminary and derived from an animal model. Further research and clinical trials are necessary to confirm these benefits in human subjects. Full article