Development Of Lesions Research Articles

High-risk human papillomavirus infection and cervical cytopathology: relationship with cervical nitric oxide levels

BackgroundNitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia.MethodsThe study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction.ResultsHigh-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5–45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2–9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6–94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6–33.3 and 34.5 µmol/mL, IQR: 11.7–61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively.ConclusionsThe high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.

Synthesis, characterization, cytotoxicity, and antiviral activity of new coumarin analogues against coronavirus

Coronaviruses have emerged as a global health challenge, with the recent outbreak of SARS-CoV-2 affecting more than 600 million individuals worldwide. While vaccination remains a central preventive approach, addressing SARS-CoV-2 involves antiviral drugs, monoclonal antibodies, and corticosteroids. Research indicates that coumarin exhibits potent antiviral properties. Therefore, this study aimed to investigate the antiviral properties of newly synthesized coumarin analogues (NCA) against coronaviruses. The study involved the synthesis of NCAs through esterification, hydrazination, imination, and cyclo-condensation reactions, followed by their characterization using FTIR, NMR, and Mass Spectrometry. Cell viability analysis was conducted using HEK-293 cells, and the viral replication inhibition activity of NCAs against OC43 was assessed using plaque assays. The antiviral activity of NCAs against the Infectious Bronchitis Virus (IBV) was evaluated based on mortality rate, lesion development, and viral RNA load suppression. The study successfully synthesized NCAs and elucidated their structures. The viral plaque assay demonstrated the ability of NCAs to effectively inhibit viral replication. Analysis of viral RNA by qRTPCR confirmed a decrease in OC43 viral load following NCA treatment. Immunofluorescence assays also showed a reduction in SARS-CoV-2 infection in the presence of NCAs. Evaluation of cytotoxicity using HEK-293 cells indicated that NCAs exhibited a favourable safety profile while effectively inhibiting IBV viral replication. These findings highlight the promising antiviral activities of NCAs against coronavirus replication and infection.

Oral Mucosa and Saliva Alterations Related to Vape.

Electronic nicotine delivery systems (e-cigarette, pod, and vape) are currently among the tobacco consumption of adolescents and young adults. The aim is to show oral mucosa and saliva alterations related to vape. A vape-user patient, presenting a white plaque in the posterior region of the hard palate, underwent clinical examination, sialometry, pH evaluation, and excisional biopsy of the white lesion. Molecular changes in saliva and vape liquid were analyzed by vibrational spectroscopy. The histopathological analyses showed hyperparakeratosis without dysplasia. Formaldehyde, ketones, and aromatic hydrocarbon species were identified in e-cig liquid by the FTIR. The use of vape may be related to the development of hyperkeratotic lesions in the oral mucosa as well as significantly modify the patient's salivary patterns as the vape liquid presents carcinogenic and cytotoxic components in its composition.

Characterization of the forehead skin microbiome in the early phase of acne.

The skin microbiota is known to be imbalanced in acne vulgaris, but the changes occurring during the early stages of acne onset remain poorly described. To characterize the skin microbiome of subclinical stages of acne in adults and adolescents. The composition and diversity of the microbiota from non-lesional skin on the forehead of subjects with mild-to-moderate acne were compared to the ones from non-acne subjects. Analyses of skin swab samples were performed using high-throughput sequencing of the V1-V3 regions of the bacterial 16S ribosomal RNA gene, the tuf gene fragment of Staphylococcus species and the internal transcribed spacer (ITS1) region of the fungal rRNA gene to determine the relative abundance, alpha-diversity and beta-diversity of bacteria and fungi. Compared with non-acne subjects, acne subjects had a higher abundance of Cutibacterium (72.4% vs. 57.8%) and lower abundances of Corynebacterium (2.8% vs. 4.8%) and Streptococcus (1.4% vs. 3.2%). Bacterial alpha- and beta-diversity indices also differed significantly between the two groups, reflecting differences in richness, evenness, abundance and phylogenetic distance between bacterial populations. Differences were also observed at the level of Staphylococcus species: S. capitis was predominant in skin samples from non-acne subjects (46.7%), whereas S. epidermidis was the most abundant Staphylococcus species in non-lesional forehead skin areas of acne subjects (44.2%). Conversely, no significant between-group differences were found for fungi, with Malasseziales being the predominant order in both subject groups. Dysbiosis was observed very early in subclinical acne stages of the forehead skin, with the overall abundance, richness and evenness of the bacterial population being lower in acne than in non-acne skin samples. Dysbiosis was also found at the level of Staphylococcus species. The development of acne lesions could therefore be prevented by using a skin care product that rebalances facial skin microbiota at very early stages.

Influence of irradiated dentin, biofilm and different artificial saliva formulations on root dentin demineralization

The aim of this study was evaluated the influence of radiation as well as of new formulations of artificial saliva on the development of root dentin lesions. Bovine root samples were divided into: irradiated (70 Gy) dentin or not; the type of biofilm (from irradiated patient-experimental or non-irradiated patient-control) and the type of artificial saliva (for the condition irradiated dentin/biofilm from irradiated patient): Control Artificial Saliva (inorganic); Control Saliva + 1 mg/ml hemoglobin; Control Saliva +0.1 mg/ml cystatin; Control Saliva + hemoglobin + cystatin; Bioextra (positive control) and deionized water (DiW, negative control) (n = 12/group). Biofilm was produced using human biofilm and McBain saliva (0.2 % of sucrose, 37o C and 5 % CO2); the treatments were done 1x/day, for 5 days. Colony-forming units (CFU) counting was performed; demineralization was quantified by transversal microradiography. Two-way ANOVA/Bonferroni or Sidak test for the comparison between biofilm x dentin and ANOVA/Tukey or Kruskal-Wallis/Dunn for comparing artificial saliva were done (p < 0.05). The type of biofilm had no influence on CFU and demineralization. Sound dentin under control biofilm presented the lowest Lactobacillus ssp. and Streptococcus mutans CFU and the lowest mean mineral loss (R) (25.6 ± 2.2; 23.7 ± 2.9 %) compared to irradiated dentin (26.1 ± 2.8; 28.1 ± 3.3, p < 0.004) for both types of biofilms (experimental and control, respectively). Bioextra was the only artificial saliva that reduced R (10.8 ± 2.5 %) and Lesion Depth (LD) (35 ± 15 μm) compared to DiW (17.3 ± 3.3 %, 81 ± 18 μm, p < 0.0001). Irradiation has impact on caries development; the experimental saliva were unable to reduce its occurrence.

CD8+ T Cells Drive Plaque Smooth Muscle Cell Dedifferentiation in Experimental Atherosclerosis.

Atherosclerosis is driven by the infiltration of the arterial intima by diverse immune cells and smooth muscle cells (SMCs). CD8+ T cells promote lesion growth during atherosclerotic lesion development, but their role in advanced atherosclerosis is less clear. Here, we studied the role of CD8+ T cells and their effects on SMCs in established atherosclerosis. CD8+ T cells were depleted in (SMC reporter) low-density lipoprotein receptor-deficient (Ldlr-/-) mice with established atherosclerotic lesions. Atherosclerotic lesion formation was examined, and single-cell RNA sequencing of aortic SMCs and their progeny was performed. Additionally, coculture experiments with primary aortic SMCs and CD8+ T cells were conducted. Although we could not detect differences in atherosclerotic lesion size, an increased plaque SMC content was noted in mice after CD8+ T-cell depletion. Single-cell RNA sequencing of aortic lineage-traced SMCs revealed contractile SMCs and a modulated SMC cluster, expressing macrophage- and osteoblast-related genes. CD8+ T-cell depletion was associated with an increased contractile but decreased macrophage and osteoblast-like gene signature in this modulated aortic SMC cluster. Conversely, exposure of isolated aortic SMCs to activated CD8+ T cells decreased the expression of genes indicative of a contractile SMC phenotype and induced a macrophage and osteoblast-like cell state. Notably, CD8+ T cells triggered calcium deposits in SMCs under osteogenic conditions. Mechanistically, we identified transcription factors highly expressed in modulated SMCs, including Runx1, to be induced by CD8+ T cells in cultured SMCs in an IFNγ (interferon-γ)-dependent manner. We here uncovered CD8+ T cells to control the SMC phenotype in atherosclerosis. CD8+ T cells promote SMC dedifferentiation and drive SMCs to adopt features of macrophage-like and osteoblast-like, procalcifying cell phenotypes. Given the critical role of SMCs in atherosclerotic plaque stability, CD8+ T cells could thus be explored as therapeutic target cells during lesion progression.

Exposure of Mice to a PFAS Mixture and Outcomes Related to Circulating Lipids, Bile Acid Excretion, and the Intestinal Transporter ASBT.

Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced impacts on enterohepatic circulation may play a critical role in cardiovascular risk. Using a mouse model with high levels of low-density and very low-density lipoprotein (LDL and VLDL, respectively) cholesterol and aortic lesion development similar to humans, the present study investigated mechanisms linking exposure to a PFAS mixture with increased cholesterol. Male and female mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFHxS, PFNA, GenX), each at a concentration of , for 7 wk. Blood was collected longitudinally for cholesterol measurements, and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA sequencing. After 7 wk of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. Total circulating cholesterol levels were higher in PFAS-exposed mice after 7 wk ( vs. in female mice and vs. in male mice exposed to vehicle or PFAS, respectively). Total circulating bile acid levels were higher in PFAS-exposed mice ( vs. in female mice and vs. in male mice exposed to vehicle or PFAS, respectively). In addition, total fecal bile acid levels were lower in PFAS-exposed mice ( vs. in females and vs. in males exposed to vehicle or PFAS, respectively). In the ileum, expression levels of the apical sodium-dependent bile acid transporter (ASBT) were higher in PFAS-exposed mice. Mice exposed to a PFAS mixture displayed higher circulating cholesterol and bile acids perhaps due to impacts on enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk following PFAS exposure. https://doi.org/10.1289/EHP14339.

Macroscopic and Histological Effects of Polycaprolactone Dermal Filler in the Orofacial Region: A Study in Rats

The objective of our study was to evaluate early and late macroscopic and histological changes associated with the use of polycaprolactone dermal filler (PCL) in the orofacial region. Forty-eight female Wistar rats were divided into the PCL group and the control group. The material was applied to the ventral tongue and submandibular region, and the animals were euthanized at three time points—24 h, and 30 and 90 days. In the PCL group, yellowish nodules were observed on the tongue at all experimental time points. At the 24 h mark, the histological analysis revealed the presence of the PCL and a predominance of lymphocytes, plasma cells, and neutrophils. At 30 and 90 days, macrophages and multinucleated giant cells predominated around the PCL spheres. Collagen density in the dermis was higher in the PCL group when compared to the control at 30 and 90 days. In the submandibular glands, an inflammatory process similar to that observed at other sites was noted, with no alterations in acinar or ductal morphology. The results of this study highlight the effectiveness of PCL as a collagen biostimulator. Nevertheless, the development of nodular lesions on the tongue signals the potential risk of complications in mobile anatomical structures.

Leaf grey spot caused by Arcopilus aureus on tobacco in China.

Tobacco (Nicotiana tabacum L.) is one of the most widely cultivated industrial crops worldwide. From April to July 2023, about 40% of tobacco seedlings in the greenhouse exhibited irregular taupe lesions in Zhengzhou, Henan Province, China. At an early stage of the lesion development, light grey spots with the diameter of 1-2 mm were observed, these spots gradually expanded and connected into large irregular lesions causing leaf wrinkling or withered. A total of 12 infected leaf tissues were sterilized with 75% ethanol for 45 s, rinsed three times in sterilized water and then plated on potato dextrose agar (PDA) medium for 10 days at 28°C in darkness. Seven fungal colonies that show the similar appearance were isolated and three of them (MB-1, MB-2 and MB-3) were used for subsequent identification. Colonies of these strains on PDA with loose mycelium and orange-red pigment on the underside, white aerial in the center and light yellow hyphae near the periphery, formed in the shape of a concentric ring pattern. Ascomata appeared from the 14th day, were black, spherical or ellipsoid with walls of textura angularis, and size was 53.8-101.1 μm × 50.3-104.3 μm (n=30). Terminal hairs were brown and straight, gradually tapering toward the tips. Asci clavate or fusiform, spore bearing part 16.2-29.2 × 7.3-11.4 μm (n=21), with 8 irregularly arranged ascospores, evanescent. Ascospores are brown at maturity, biapiculate, navicular or fusiform shapes with size of 8.7-12.8 μm × 4.8-6.9 μm (n=100), and more or less inaequilateral. Single spore strains derived from these strains exhibited the morphological features consistent with the original strains. The morphological characteristics of the fungus were consistent with the description of Arcopilus aureus (Chivers) X.W. Wang & Samson (= Chaetomium aureum Chivers) (Lee et al. 2019). Furthermore, the sequences of RPB2 region were amplified from these strains and the result sequences (GenBank accession no. OR513105-OR513108) all showed a 100.00% identity with A. aureus strain CBS 538.73 (GenBank accession no. KX976807.1). It was reported that the RPB2 gene was efficient in discriminating Arcopilus species (Tavares et al. 2022), thus a maximum likelihood (ML) phylogenetic tree based on the RPB2 gene sequences were constructed using MEGA 7.0 with 1000 replications of bootstrapping (Kumar et al. 2016), which revealed that these strains formed a well-supported clade with A. aureus strains of (CBS 153.52 and CBS538.73) (Wang et al. 2022). Pathogenicity analysis were performed on healthy flue-cured tobacco seedlings leaves (cv Y85) by using mycelial agar plugs (5 mm in diameter) and spore suspension (1×106 spores/mL), and the PDA plugs and sterile water were used for control group, respectively. Tobacco seedlings were incubated in a 25°C and 70% RH growth chamber. After seven days, the leaves showed obvious symptoms, with taupe lesions and yellow halos on the periphery, whereas no symptoms were found on the control leaves. The A. aureu was then reisolated from inoculated diseased leaves. Previously, A. aureus has been only reported to cause leaf black disease on Pseudostellaria heterophylla in China (Yuan et al. 2021). To our knowledge, this is the first reported of A. aureus causing tobacco leaf grey spot worldwide. Arcopilus aureus has been reported as a plant biocontrol fungus (Wang et al. 2013). However, due to the potential serious damage in tobacco seedlings caused by this fungus, the use of A. aureus as a plant biocontrol agent needs to be given more attention, and disease control measures of this pathogen should be developed.

Exploring the Antifungal Efficacy of Essential Oils against Alternaria solani, the Causative Pathogen of Early Leaf Blight in Tomato Plants

Alternaria solani is an important necrotrophic fungus that is responsible for the early blight disease which is a common disease in tomato fields. In this research, the antifungal activity of essential oils extracted from Satureja hortensis, Thymbra spicata, Thymus sipyleus, Origanum majorana, O. syriacium, O. onites, O. vulgar, Artemisia absinthium, A. santonicum and A. spicigera were tested against Alternaria solani the causative agent of Tomato early blight disease. The study was carried out in two different ways, in vitro and in vivo. In vitro studies were conducted on media mixed with essential oils, and different concentrations of oils were examined on fungal growth in petri dishes. In in vivo studies, the effects of essential oils on the development of disease lesions were evaluated by infecting healthy tomato fruits. The concentrations used in the study were 140, 280, 560 and 1000 µl/L in the in vitro and 2.5, 5, 10 and 20 µl/fruit under in vivo conditions. Among the in vitro trials, the essential oils extracted from Thymus sipyleus and O. onites exhibited the most pronounced antifungal efficacy, achieving complete growth inhibition of the fungal pathogen across all concentrations whereas the essential oils from Artemisia spicigera and A. santonicum displayed relatively lower efficacy compared to the other oils. Conversely, under in vivo conditions, the essential oils derived from O. majorana and A. absinthium demonstrated the greatest capacity to impede the development of disease lesions on the fruit, yielding inhibition rates of 84% and 64% at 2.5 µl per fruit concentrations, respectively. In contrast the essential oils from Artemisia spicigera and A. santonicum had the least effect on the development of the disease, as there was disease lesions appeared even on the fruits that were applied at 20µl/fruit doses. Although most of the essential oils had some degree of antifungal action, still much effort is needed to put on both in vitro and in vivo trials to strength the reliability and consistency of the future related researches.

Aberrant DNA methylation associated with the development of metabolic dysfunction-associated fatty liver disease

The literature review deals with DNA methylation, a key epigenetic mechanism that controls the activity of gene transcription, plays a decisive role in the formation of genomic imprinting, gene silencing, X-chromosome inactivation, RNA splicing, DNA repair, cell differentiation and cell reprogramming, and also determines the occurrence and development of liver steatotic lesions and metabolic disorders. Methylation of DNA cytosine dinucleotide (CpG) can be represented in two types: de novo CpG methylation, which is carried out by 5mC DNA writers — DNA-(cytosine-5)-methyltransferase (DNMT) 3a and 3b, and suppor­ting DNA methylation, which is performed by DNMT1 during DNA replication. It has been found that the maintenance DNA methylation allows the preservation of the methylation pattern characteristic of progenitor cells in the cells of the new generation, and the DNA methylation of the gene body is associated with its increased expression. Active demethylation of 5mC is carried out by TET dioxygenases, including three enzymatic representatives: TET1, TET2 and TET3. It has been demonstrated that aberrant methylation of DNA nucleotides is directly related to the activity of lipid synthesis, the degree of oxidative stress, the development of liver steatosis, low-grade inflammation, insulin resistance, and the progression of liver fibrosis. The authors presented in detail the functions and features of DNA methyltransferases, erasers, and readers of 5mC sites; possible violations of the balance of activity of writers and erasers of 5mC DNA; DNA methylation landscape and patterns; clinical significance of DNA methylation signatures in metabolic dysfunction-associated fatty liver disease. Global hypomethylation of genome, at least 55 genes, is observed in patients with metabolic dysfunction-associated fatty liver disease. The authors emphasize that the use of DNA methylation signatures is a promising direction for early diagnosis and prognosis of the course of metabolic dysfunction-associated fatty liver disease, while the study of molecular components of DNA methylation mechanisms involved in the regulation of gene expression, the dependence of their activity on exposure to the exposome will allow to persona­lize and improve recommendations for lifestyle and diet modification in patients with metabolic dysfunction-associated fatty liver disease.

Telomere Length, Telomerase Activity, and Vaginal Microbiome in Patients with HPV-Related Precancerous Lesions.

Persistent high-risk human papillomaviruses (HR HPVs) infection leads to the development of squamous intraepithelial lesions in cervical cells that may lead to cancer. The telomere length, telomerase activity, and species composition of the vaginal microbiome may influence the dynamic of changes and the process of carcinogenesis. In the present study, we analyze relative telomere length (RTL), relative hTERT expression (gene for the telomerase component-reverse transcriptase) in cervical smear cells and vaginal microbiomes. Total RNA and DNA were isolated from tissue samples of 109 patients from the following groups: control, carrier, low-grade or high-grade squamous intraepithelial lesion (L SIL and H SIL, respectively), and cancer. The quantitative PCR method was used to measure telomere length and telomerase expression. Vaginal microbiome bacteria were divided into community state types using morphotype criteria. Significant differences between histopathology groups were confirmed for both relative telomere length and relative hTERT expression (p < 0.001 and p = 0.001, respectively). A significant difference in RTL was identified between carriers and H SIL (p adj < 0.001) groups, as well as between carriers and L SIL groups (p adj = 0.048). In both cases, RTL was lower among carriers. The highest relative hTERT expression level was recorded in the H SIL group, and the highest relative hTERT expression level was recorded between carriers and the H SIL group (p adj < 0.001). A correlation between genotype and biocenosis was identified for genotype 16+A (p < 0.001). The results suggest that identification of HPV infection, telomere length assessment, and hTERT expression measurement together may be more predictive than each of these analyses performed separately.

Efficacy of rituximab in the treatment of epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous disease that is mediated by antibodies that bind collagen VII. The treatment of EBA can be challenging and often multiple immunomodulatory drugs are required. Rituximab has been reported to be an effective treatment for recalcitrant EBA, although its evidence base is limited to case reports and case series. This study therefore aimed to evaluate the efficacy of rituximab in patients with EBA. EBA patients treated with rituximab were identified by searching electronic medical records. Diagnostic criteria for EBA were as follows; mechanobullous skin lesions and / or mucosal ulceration, indirect immunofluorescence localising to the base of salt split skin and positive collagen VII antibodies. Clinical disease activity, collagen VII antibody levels and serum immunoglobulins were recorded at each follow up visit over 600 day period. Treatment responses were classified as follows; complete remission (CR) as the absence of new or established lesions on minimal therapy for 2 months, partial remission (PR) as transient lesions that heal within 1 week on minimal therapy and active disease (AD) as the development of new lesions. 14 patients with EBA were treated with rituximab. CR or PR was observed in 11 patients, and the duration of response varied between 4 and 24 months. A reduction in collagen VII antibody levels was observed in all patients. No significant adverse events were reported. Rituximab is a safe and effective treatment for patients with recalcitrant EBA although there was significant heterogeneity in the disease response.

Single nucleotide polymorphism rs4961 in the adducin 1 gene is not associated with gastric cancer or preneoplastic cancer lesions.

Gastric cancer (GC) is the fourth most deadly cancer globally. The adducin 1 (ADD1) protein is involved in oncogenic signal transduction pathways in several types of cancer, and the rs4961 variant (c.1378 G>T, p.Gly460Trp) of the ADD1 gene is associated with salt-sensitive hypertension, renal cell cancer and breast cancer susceptibility; however, it has not been investigated in GC. The aim of the present study was to evaluate the association between the rs4961 variant and the development of GC and preneoplastic gastric lesions (PGLs) in a population from western Mexico. A total of 225 individuals who underwent an endoscopy were evaluated, of which 71 patients had histopathologically diagnosed GC and 53 patients had PGLs, with 101 patients used as controls. The rs4961 variant was genotyped by using PCR and DNA sequencing. The frequency of the mutated homozygous genotype (TT) of the rs4961 variant was <10% in the three evaluated groups, and the frequency of the minor allele (T) was <21% in the GC, PGL and control groups. Genotypic and allelic frequencies were similarly distributed in all of the studied groups (P>0.05). In summary, in the study population, the rs4961 variant was not associated with GC risk; however, its role in other populations and in other types of cancer is worthy of future research.

Deficiency in Ever2 does not increase susceptibility of mice to pathogenesis by the mouse papillomavirus, MmuPV1.

Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder that is characterized by the development of papillomavirus-induced skin lesions that can progress to squamous cell carcinoma (SCC). Certain high-risk, cutaneous β-genus human papillomaviruses (β-HPVs), in particular HPV5 and HPV8, are associated with inducing EV in individuals who have a homozygous mutation in one of three genes tied to this disease: EVER1, EVER2, or CIB1. EVER1 and EVER2 are also known as TMC6 and TMC8, respectively. Little is known about the biochemical activities of EVER gene products or their roles in facilitating EV in conjunction with β-HPV infection. To investigate the potential effect of EVER genes on papillomavirus infection, we pursued in vivo infection studies by infecting Ever2-null mice with mouse papillomavirus (MmuPV1). MmuPV1 shares characteristics with β-HPVs including similar genome organization, shared molecular activities of their early, E6 and E7, oncoproteins, the lack of a viral E5 gene, and the capacity to cause skin lesions that can progress to SCC. MmuPV1 infections were conducted both in the presence and absence of UVB irradiation, which is known to increase the risk of MmuPV1-induced pathogenesis. Infection with MmuPV1 induced skin lesions in both wild-type and Ever2-null mice with and without UVB. Many lesions in both genotypes progressed to malignancy, and the disease severity did not differ between Ever2-null and wild-type mice. However, somewhat surprisingly, lesion growth and viral transcription was decreased, and lesion regression was increased in Ever2-null mice compared with wild-type mice. These studies demonstrate that Ever2-null mice infected with MmuPV1 do not exhibit the same phenotype as human EV patients infected with β-HPVs.IMPORTANCEHumans with homozygous mutations in the EVER2 gene develop epidermodysplasia verruciformis (EV), a disease characterized by predisposition to persistent β-genus human papillomavirus (β-HPV) skin infections, which can progress to skin cancer. To investigate how EVER2 confers protection from papillomaviruses, we infected the skin of homozygous Ever2-null mice with mouse papillomavirus MmuPV1. Like in humans with EV, infected Ever2-null mice developed skin lesions that could progress to cancer. Unlike in humans with EV, lesions in these Ever2-null mice grew more slowly and regressed more frequently than in wild-type mice. MmuPV1 transcription was higher in wild-type mice than in Ever2-null mice, indicating that mouse EVER2 does not confer protection from papillomaviruses. These findings suggest that there are functional differences between MmuPV1 and β-HPVs and/or between mouse and human EVER2.

Construction and validation of predictive models for intravenous immunoglobulin-resistant Kawasaki disease using an interpretable machine learning approach.

Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development. This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIG-resistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIG-resistance. A nonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment of Kawasaki disease.

A pH-sensitive, renewable invisible orthodontic aligners coating manipulates antibacterial and in situ remineralization functions to combat enamel demineralization.

During invisalign treatment, as salivary proteins or glycoproteins fill the space between the teeth and the aligners, they can easily adhere to the teeth, forming an acquired cellular film on which bacteria are highly susceptible to colonizing, which in turn leads to the development of enamel white staining lesions (WSLs), one of the major complications of orthodontic treatment. Inhibiting the activity of cariogenic bacteria while promoting the remineralization of demineralized enamel is the key to preventing and treating WSLs. Currently, the drug commonly used in clinical practice for the treatment of WSLs is silver diamine fluoride, which, although it has both antimicrobial and remineralizing effects, suffers from problems such as pulpal irritation and tooth discoloration. In this study, based on the principle of coordination chemistry, copper ions and plant polyphenol tannins were assembled on invisible orthodontic aligners to form a metal-phenol network coating (TA-Cu MPNs), and zwitterionic sulfonamethyldopamine was introduced for bionic mineralization to obtain the multifunctional coating TA-Cu MPNs@ZDS@CaP (TZC). The coating exhibits acid-responsive release of Ca2+ and PO4 3-, and the decomposed CaP layer can be regenerated by a simple dipping method. The TZC coating strongly inhibits common cariogenic bacteria and their biofilms. In addition, the results of the in vitro mineralization experiment show that TZC-coated invisible orthodontic aligner treatment of demineralized enamel has significant remineralization effects. It is worth mentioning that the constructed coating has a durable antibacterial effect and can meet the service cycle of invisible orthodontic aligners. This study provides theoretical and experimental bases for the prevention or treatment of WSLs in invisible orthodontic treatment.

Cancer Chemopreventive Effect of 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone on Diethylnitrosamine-Induced Early Stages of Hepatocarcinogenesis in Rats.

2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation.

Recurrent spontaneous pneumothorax secondary to lung cystic lesions in a case of convalescent COVID-19: a case report and literature review

BackgroundWhile spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored.Case presentation and literature reviewAn 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed “bulla” or “pneumatocele”, and one cystic lesion with air-fluid level, referred to as “pneumo-hamatocele” (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18–35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered.ConclusionsRecurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax.

Factors influencing high cardiovascular risk in subpopulation of young adults

Abstract Introduction The cardiovascular risk factors determine the development of early atheriosclerotic lesions, and the susceptibility to their proartheriosclerotic action is programmed by external factors and also those present during fetal development. The occurrence of atherosclerotic risk factors depends on an age. In population of children and young adults it seems reasonable to assess the classical risk factors for atherosclerosis in the connection with such additional given as family history being an indirect surrogate of genetic factors, and a low birth weight. Aim of the study was to categorize the study group into two groups - those who exhibit a low-risk and those who exhibit a high-risk of cardiovascular disease, and to determine the factors characteristic for each risk group. Materials and Methods The study was done on 512 volunteers, students in the following Faculties: Health Care Faculty: Nursing Course (178 / 34,7%), Physiotherapy Course (109 / 21,3%), Obstetrics Course (49 / 9,5%), Faculty of Medicine (176 / 34,3%). The questionnaire on cardiovascular risk factors was constructed. According to the results of its assessment the following groups were divided: the group of high risk (10% of investigated with the highest awarding of points) and the group of low risk (10% of investigated with the lowest awarding of points). Results Significant quantitative and qualitative differences were found between the low-risk and high-risk groups. Groups of the high and low risk did not differ in respect of sexes investigated and in respect of the direction of studies. One ascertained essential differences in variable qualitative and quantitative between the group of the low and high risk. Family history of diabetes, arterial hypertension, cardiovascular diseases, lipid disturbances, stroke were indeed greater in the group of high risk. The low birth weight was significantly lower in the group of high risk (p=0,02). The current and chronic stress status grading according to the punctual scale (0-10) was significantly higher in the group of high risk as compared to the low risk group (p=0,01, p=0,03, respectively). The systolic pressure was significantly higher in the high risk group in comparison to the low risk subjects (p=0,01). Conclusions High cardiovascular risk in subgroup of young adults results from high smoking status, low physical activity, diet and family history of cardiovascular disorders. The numerous cardiovascular risk factors that occur in some students are associated with low birth weight and a positive family medical history. The above observations show the influence of genetic and fetal factors on the development of atherosclerosis. Young adults with high cardiovascular risk are characterized by higher subjective stress level. Quantitative differences in high risk Medical family history