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Dentistry Journal May 2024This review's objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic... (Review)
Review
This review's objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic databases (Scopus and PubMed) were searched for published scientific articles following PRISMA principles. Articles eligible for inclusion in this review had to be published in English between 2017 and 2023, be original studies, and involve human subjects. Fifteen studies were included in this review: three examining oral symptoms of vitamin B12 deficiency; one assessing vitamin B complex and vitamin E for recurrent oral ulcers; one investigating serum vitamin D levels in recurrent aphthous stomatitis patients; three exploring hypovitaminosis effects on dental caries; two measuring blood serum vitamin D levels; one evaluating vitamin B12 hypovitaminosis; three investigating hypovitaminosis as indicative of gingival disease; one focusing on vitamin deficiencies and enamel developmental abnormalities; one assessing vitamin deficiencies in oral cancer patients; one examining vitamin K as an oral anticoagulant and its role in perioperative hemorrhage; and one evaluating vitamin effects on burning mouth syndrome. Despite some limitations, evidence suggests a correlation between vitamin deficiencies and oral symptoms. This systematic review was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) database (202430039).
PubMed: 38920853
DOI: 10.3390/dj12060152 -
Frontiers in Endocrinology 2024Glycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5-anhydroglucitol-6-phosphate in...
INTRODUCTION
Glycogen storage disease type 1b (GSD-1b) is characterized by neutropenia and neutrophil dysfunction generated by the accumulation of 1,5-anhydroglucitol-6-phosphate in neutrophils. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, facilitate the removal of this toxic metabolite and ameliorate neutropenia-related symptoms, including severe infections and inflammatory bowel disease (IBD). Our case series presents the treatment of three pediatric GSD-1b patients with empagliflozin over a follow-up of three years; the most extended reported follow-up period to date.
CASES DESCRIPTION
A retrospective analysis of empagliflozin treatment of three pediatric GSD-1b patients (two male and one female; ages at treatment initiation: 4.5, 2.5 and 6 years) was performed. Clinical and laboratory data from a symmetrical period of up to three years before and after the therapy introduction was reported. Data on the clinical course of the treatment, IBD activity, the need for antibiotic treatment and hospitalizations, neutrophil count and function, and markers of inflammation were assessed. Prior the introduction of empagliflozin, patients had recurrent oral mucosa lesions and infections, abdominal pain, and anemia. During empagliflozin treatment, the resolution of aphthous stomatitis, termination of abdominal pain, reduced frequency and severity of infections, anemia resolution, increased appetite, and improved wound healing was observed in all patients, as well as an increased body mass index in two of them. In a patient with IBD, long-term deep remission was confirmed. An increased and stabilized neutrophil count and an improved neutrophil function enabled the discontinuation of G-CSF treatment in all patients. A trend of decreasing inflammation markers was detected.
CONCLUSIONS
During the three-year follow-up period, empagliflozin treatment significantly improved clinical symptoms and increased the neutrophil count and function, suggesting that targeted metabolic treatment could improve the immune function in GSD-1b patients.
Topics: Humans; Male; Benzhydryl Compounds; Female; Glucosides; Glycogen Storage Disease Type I; Child; Child, Preschool; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 38919482
DOI: 10.3389/fendo.2024.1365700 -
Scientific Reports Jun 2024Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing...
Viral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe surrogate system to interrogate the function, evolution, and antigenicity of viral glycoproteins from viruses that are difficult to manipulate or those requiring high biosafety level containment. However, the production of recombinant VSV can be technically challenging. In this work, we present an efficient and robust plasmid-based system for the production of recombinant VSV encoding foreign glycoproteins. We validate the system using glycoproteins from different viral families, including arenaviruses, coronaviruses, and hantaviruses, as well as highlight their utility for studying the effects of mutations on viral fitness. Overall, the methods described herein can facilitate the study of both native and recombinant VSV encoding foreign glycoproteins and can serve as the basis for the production of VSV-based vaccines.
Topics: Plasmids; Glycoproteins; Animals; Humans; Vesiculovirus; Viral Proteins; HEK293 Cells
PubMed: 38918479
DOI: 10.1038/s41598-024-65384-8 -
Microbiology Spectrum Jun 2024The rapidly developing field of oncolytic virus (OV) therapy necessitates the development of new and improved analytical approaches for the characterization of the virus...
UNLABELLED
The rapidly developing field of oncolytic virus (OV) therapy necessitates the development of new and improved analytical approaches for the characterization of the virus during production and development. Accurate monitoring and absolute quantification of viral proteins are crucial for OV product characterization and can facilitate the understanding of infection, immunogenicity, and development stages of viral replication. Targeted mass spectrometry methods like multiple reaction monitoring (MRM) offer a robust way to directly detect and quantify specific targeted proteins represented by surrogate peptides. We have leveraged the power of MRM by combining ultra-high performance liquid chromatography (UPLC) with a Sciex 6500 triple-stage quadrupole mass spectrometer to develop an assay that accurately and absolutely quantifies the structural proteins of a pseudotyped vesicular stomatitis virus (VSV) intended for use as a new biotherapeutic (designated hereafter as VSV-GP to differentiate it from native VSV). The new UPLC-MRM method provides absolute quantification with the use of heavy-labeled reference standard surrogate peptides. When added in known exact amounts to standards and samples, the reference standards normalize and account for any small perturbations during sample preparation and/or instrument performance, resulting in accurate and precise quantification. Because of the multiplexed nature of MRM, all targeted proteins are quantified at the same time. The optimized assay has been enhanced to quantify the ratios of the processed GP1 and GP2 proteins while simultaneously measuring any remaining or unprocessed form of the envelope protein GP complex (GPC; full-length GPC).
IMPORTANCE
The development of oncolytic viral therapy has gained considerable momentum in recent years. Vesicular stomatitis virus glycoprotein (VSV-GP) is a new biotherapeutic emerging in the oncolytic viral therapy platform. Novel analytical assays that can accurately and precisely quantify the viral proteins are a necessity for the successful development of viral vector as a biotherapeutic. We developed an ultra-high performance liquid chromatography multiple reaction monitoring-based assay to quantify the absolute concentrations of the different structural proteins of VSV-GP. The complete processing of GP complex (GPC) is a prerequisite for the infectivity of the virus. The assay extends the potential for quantifying full-length GPC, which provides an understanding of the processing of GPC (along with the quantification of GP1 and GP2 separately). We used this assay in tracking GPC processing in HEK-293-F production cell lines infected with VSV-GP.
PubMed: 38916347
DOI: 10.1128/spectrum.03651-23 -
BioRxiv : the Preprint Server For... Jun 2024The cellular enzyme poly (ADP-ribose) polymerase-1 (PARP-1) regulates multiple processes that are potentially implicated in HIV-1 infection. However, the role of PARP-1...
UNLABELLED
The cellular enzyme poly (ADP-ribose) polymerase-1 (PARP-1) regulates multiple processes that are potentially implicated in HIV-1 infection. However, the role of PARP-1 in HIV-1 infection remains controversial, with reports indicating or excluding that PARP-1 influence early steps of the HIV-1 life cycle. Most of these studies have been conducted with Vesicular Stomatitis virus Glycoprotein G (VSV-G)-pseudotyped, single-round infection HIV-1; limiting our understanding of the role of PARP-1 in HIV-1 replication. Therefore, we evaluated the effect of PARP-1 deficiency or inhibition in HIV-1 replication in human CD4+ T cells. Our data showed that PARP-1 knockout increased viral replication in SUP-T1 cells. Similarly, a PARP-1 inhibitor that targets PARP-1 DNA-binding activity enhanced HIV-1 replication. In contrast, inhibitors affecting the catalytic activity of the enzyme were inactive. In correspondence with the pharmacological studies, mutagenesis analysis indicated that the DNA-binding domain was required for the PARP-1 anti-HIV-1 activity, but the poly-ADP-ribosylation activity was dispensable. Our results also demonstrated that PARP-1 acts at the production phase of the viral life cycle since HIV-1 produced in cells lacking PARP-1 was more infectious than control viruses. The effect of PARP-1 on HIV-1 infectivity required Env, as PARP-1 deficiency or inhibition did not modify the infectivity of Env-deleted, VSV-G-pseudotyped HIV-1. Furthermore, virion-associated Env was more abundant in sucrose cushion-purified virions produced in cells lacking the enzyme. However, PARP-1 did not affect Env expression or processing in the producer cells. In summary, our data indicate that PARP-1 antagonism enhances HIV-1 infectivity and increases levels of virion-associated Env.
IMPORTANCE
Different cellular processes counteract viral replication. A better understanding of these interfering mechanisms will enhance our ability to control viral infections. We have discovered a novel, antagonist effect of the cellular enzyme poly (ADP-ribose) polymerase-1 (PARP-1) in HIV-1 replication. Our data indicate that PARP-1 deficiency or inhibition augment HIV-1 infectivity in human CD4+ T cells, the main HIV-1 target cell . Analysis of the mechanism of action suggested that PARP-1 antagonism increases in the virus the amounts of the viral protein mediating viral entry to the target cells. These findings identify for the first time PARP-1 as a host factor that regulates HIV-1 infectivity, and could be relevant to better understand HIV-1 transmission and to facilitate vaccine development.
PubMed: 38915699
DOI: 10.1101/2024.06.11.598467 -
Journal of Virological Methods Jun 2024We evaluated the use of the Product Enhanced Reverse Transcriptase (PERT) assay as a means of detecting virus in retroviral vectors products pseudotyped with Gibbon Ape...
We evaluated the use of the Product Enhanced Reverse Transcriptase (PERT) assay as a means of detecting virus in retroviral vectors products pseudotyped with Gibbon Ape Leukemia Virus (GALV) and Vesicular Stomatitis Virus G (VSVG) envelopes. PERT provides greater standardization than the S+/L- assay which has been used extensively in virus detection. A challenge is that PERT will also detect residual retroviral vectors as vector particles contain reverse transcriptase. Vector products were cultured for 3 weeks on HEK293 cells to amplify any potential virus. In addition, vector supernatant and end-of-production cells were spiked with GALV to evaluate for inhibition by the test article. Results of PERT and the S+/L- assay were compared. PERT and S+/L- assays were both effective in detecting virus. Vector supernatants were negative at the end of 3 weeks of culture by PERT for both GAVL and VSVG pseudotyped vector. In contrast, end-of-production cells were positive by PERT due to persistent vector producing cells. A one-week culture of cell-free media obtained at the 3 weeks timepoint allowed distinction of virus-free test articles from those with virus. The PERT assay is suitable for detecting replication competent retrovirus in vector products pseudotyped with GALV and VSVG envelopes.
PubMed: 38908550
DOI: 10.1016/j.jviromet.2024.114988 -
European Journal of Dermatology : EJD Apr 2024
Topics: Humans; Colchicine; Recurrence; Female; Stomatitis, Aphthous; Administration, Oral; Adult; Ulcer; Lymphadenitis
PubMed: 38907559
DOI: 10.1684/ejd.2024.4653 -
Critical Reviews in Oncology/hematology Jun 2024Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and... (Review)
Review
CONTEXT
Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.
OBJECTIVE
To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.
EVIDENCE ACQUISITION
A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs).
EVIDENCE SYNTHESIS
Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.
CONCLUSIONS
Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.
PubMed: 38906514
DOI: 10.1016/j.critrevonc.2024.104420 -
Molecular Biology Reports Jun 2024Senecavirus A (SV-A) is an RNA virus that belongs to the genus Senecavirus within the family Picornaviridae. This study aimed to analyze factors that can influence the...
BACKGROUND
Senecavirus A (SV-A) is an RNA virus that belongs to the genus Senecavirus within the family Picornaviridae. This study aimed to analyze factors that can influence the molecular diagnosis of Senecavirus A, such as oligonucleotides, RNA extraction methods, and RT-qPCR kits.
METHODS
Samples from suspected cases of vesicular disease in Brazilian pigs were analyzed for foot-and-mouth disease, swine vesicular disease, and vesicular stomatitis. All tested negative for these diseases but positive for SV-A. RT-qPCR tests were used, comparing different reagent kits and RNA extraction methods. Sensitivity and repeatability were evaluated, demonstrating efficacy in detecting SV-A in clinical samples.
RESULTS
In RNA extraction, significant reduction in Cq values was observed with initial dilutions, particularly with larger supernatant volumes. Trizol and Maxwell showed greater sensitivity in automated equipment protocols, though results varied in tissue tests. RT-qPCR kit comparison revealed differences in amplification using viral RNA but minimal differences with plasmid DNA. Sensitivity among methods was comparable, with slight variations in non-amplified samples. Repeatability tests showed consistent results among RT-qPCRs, demonstrating similarity between methods despite minor discrepancies in Cq values.
CONCLUSIONS
Trizol, silica columns, and semi-automated extraction were compared, as well as different RT-qPCR kits. The study found significant variations that could impact the final diagnosis.
Topics: Animals; Picornaviridae; Swine; Picornaviridae Infections; RNA, Viral; Swine Diseases; Sensitivity and Specificity; Real-Time Polymerase Chain Reaction; Swine Vesicular Disease; Foot-and-Mouth Disease; Brazil; Reproducibility of Results
PubMed: 38904698
DOI: 10.1007/s11033-024-09692-2 -
Cureus Jun 2024Heat-activated polymethyl methacrylate (PMMA) is the most common and widely accepted denture base material. Two important drawbacks are the development of denture...
Comparative Evaluation of the Flexural Strength of Heat-Activated Polymethyl Methacrylate Denture Base Resin With and Without 0.2% by the Weight of Silver Nanoparticles Cured by Conventional and Autoclave Methods: An In Vitro Study.
PURPOSE
Heat-activated polymethyl methacrylate (PMMA) is the most common and widely accepted denture base material. Two important drawbacks are the development of denture stomatitis and the high incidence of fracture of denture bases. The present study investigated the effect of adding 0.2% by weight of silver nanoparticles (AgNps) and using the autoclave method of terminal boiling on the flexural strength of heat-activated PMMA denture base resin.
METHODS
A total of 40 samples of heat-activated PMMA blocks were divided into four groups, with 10 samples (n = 10) in each group. Group 1 consisted of unmodified heat-activated PMMA resin (PMMA-1) polymerized by the conventional method of terminal boiling (conventional curing); Group 2 consisted of 0.2% by weight AgNPs added to heat-activated PMMA resin (PMMA-2) polymerized by conventional curing; Group 3 consisted of PMMA-1 polymerized by the autoclave method of terminal boiling (autoclave curing); and Group 4 consisted of PMMA-2 polymerized by autoclave curing. The flexural strength was tested using a universal testing machine. Descriptive statistics were expressed as mean ± SD and median flexural strength. Kruskal-Wallis ANOVA with Mann-Whitney U post hoc test was applied to test for statistical significance between the groups. The level of significance was set at p<0.05.
RESULTS
The results showed a statistically significant reduction in flexural strength in Group 2 compared to Group 1. The samples from Group 4 showed a statistically significant increase in flexural strength compared to Group 2. The Group 4 denture base had the highest flexural strength (115.72 ± 7.27 MPa) among the four groups, followed by Group 3 (104.16 ± 4.85 MPa). The Group 1 samples gave a flexural strength of 101.45 ± 3.13 MPa, and Group 2 gave the lowest flexural strength (85.98 ± 3.49 MPa) among the four groups tested.
CONCLUSION
The reduction in flexural strength of the heat-activated PMMA denture base after adding 0.2% by weight of AgNP as an antifungal agent was a major concern among manufacturers of commercially available denture base materials. It was proved in the present study that employing the autoclave curing method of terminal boiling for the polymerization of 0.2% by weight of AgNp-added heat-activated PMMA denture base resulted in a significantly higher flexural strength compared to the conventional curing method of terminal boiling for polymerization. Unmodified heat-activated PMMA gave higher flexural strength values when polymerized by autoclave curing compared to the conventional curing method of terminal boiling.
PubMed: 38903978
DOI: 10.7759/cureus.62675