Predominant Disease Research Articles

Evaluation of pulmonary tuberculosis disease burden in Shenyang, China, 2023.

Pulmonary tuberculosis (PTB) is one of the most serious infectious diseases worldwide and poses a great threat to people's health. China has a vast territory with substantial regional disparities in the PTB disease burden. However, there have been no studies conducted to evaluate the PTB disease burden in Shenyang. The aim was to elucidate the magnitude, composition, and distribution of PTB disease burden in Shenyang. The disability-adjusted life years (DALYs) calculated based on Global Burden of Disease (GBD) framework was used to assess the disease burden of PTB in Shenyang in 2023, and descriptive epidemiological methods were employed to elucidate the magnitude, composition, and distribution characteristics of PTB disease burden in Shenyang. In 2023, 4,169 PTB cases were reported in Shenyang, including 2,901 males and 1,268 females. The incidence of PTB was 45.50/105, of which 64.29/105 for males and 27.30/105 for females. The incidence among males was higher than that among females (X2 = 688.56, p<0.001). The highest incidence was 107.00/105 in the group of the population aged 80 and above (X2 = 1171.75, p<0.001). In 2023, 189 PTB deaths were reported in Shenyang, including 156 males and 33 females. The mortality of PTB was 2.06/105 of which 3.46/105 for males and 0.71/105 for females. The mortality among males was higher than that among females (X2 = 83.69, p<0.001). The highest mortality was 16.04/105 in the group of the population aged 80 and above (X2 = 285.61, p<0.001). The PTB DALYs rate was 58.25/105, of which 91.73/105 for males and 21.22/105 for females. The DALYs rate among males was higher than that among females (X2 = 44.04, p<0.001). The highest DALYs rate was 149.86/105 in the group of the population aged 80 and above (X2 = 305.35, p<0.001). Years of life lost (YLLs) due to PTB accounted for 71.38% of total DALYs, of which 74.33% for males and 52.89% for females. The PTB DALYs rate in Shenyang was 58.25/105, which was lower than that in China, equivalent to 80% of the national PTB disease burden rate. The disease burden showed a characteristic of increasing with age, and the PTB DALYs rate for males was higher than that for females, being equivalent to 4 times the female rate. The predominant disease burden of PTB was attributed to YLLs, accounting for as much as 71.38%, indicating that PTB primarily results in premature mortality rather than disability. Therefore, the focus should be shifted towards early intervention to reduce transmission, especially for the aged males.

Liver sinusoidal endothelial cells: Friend or foe in metabolic dysfunction- associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the predominant liver disease and is becoming the paramount contributor to end-stage liver disease and liver-related deaths. Liver sinusoidal endothelial cells (LSECs) located between the hepatic parenchyma and blood from viscera and gastrointestinal tract are the gatekeepers for the hepatic microenvironment and normal function. In normal physiological conditions, LSECs govern the substance exchange between hepatic parenchyma and blood through dynamic regulation of fenestration and maintain the quiescent state of Kupffer cells (KCs) and hepatic stellate cells. In MASLD, lipotoxicity, insulin resistance, gastrointestinal microbiota dysbiosis, and mechanical compression caused by fat-laden hepatocytes result in LSECs capillarization and dysfunction. The altered LSECs progressively shift from healer to injurer, exacerbating liver inflammation and advancing liver fibrosis. This review focuses on the deteriorative roles of LSECs and related molecular mechanisms involved in MASLD and their contribution to metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis development and progression. Furthermore, in this review, we propose that targeting LSECs dysfunction is a prospective therapeutic strategy to restore the physiological function of LSECs and mitigate MASLD progression.

Joint analysis of genome-wide cross-trait and multi-omics reveals molecular mechanisms of inflammatory bowel disease and nominates its novel therapeutic genes.

Inflammatory bowel disease (IBD) with the two predominant endophenotypes-Crohn's disease (CD) and ulcerative colitis (UC)-represents a group of chronic gastrointestinal inflammatory conditions. Since most genetic associations with IBD are often limited to independent subtypes, we reported a genome-wide association study (GWAS) cross-trait analysis combined with CD and UC to enhance statistical power. Initially, we detected 256 association signals at 54 genomic susceptibility loci and further characterized the functionality of variants within these regions. Subsequently, we revealed tissue and cell-specific heritability enrichment, particularly in whole blood, small intestine terminal ileum, spleen, lung, and colon transverse. Leveraging multi-omics datasets, we adopted a two-pronged approach comprising summary data-based Mendelian randomization (SMR) and transcriptome-wide association study (TWAS) to pinpoint likely causal genes and variants. Further, RNA-seq analysis facilitated the evaluation of differential expression and co-expression in intestinal tissues. Through a multi-stage prioritization strategy, compelling evidence for putative targets was nominated; notably highlighting several potential susceptibility genes such as IL27 and SBNO2. Finally, we utilized Mendelian randomization (MR) analysis with diverse datasets to verify the convergence of these two endophenotype-driven genes. Our investigation yields valuable insights to inform genetic mechanisms in IBD and reveal potential causal gene targets.

Outcome of critically ill patients receiving systemic chemotherapy on the intensive care unit.

Analyze the outcomes of critically ill patients who developed new-onset organ dysfunction and received systemic chemotherapy during their ICU stay. Retrospective cohort study. A tertiary medical center in Germany with an Intensive Care Medicine department consists of 11 intensive care units comprising 140 beds, serving all subspecialties of adult intensive care medicine. 167 patients receiving systemic oncological treatment from January 1st, 2015 to December 31st, 2021, with a data cut-off on December 31st, 2022. None. A total of 167 patients were included. The primary reasons for ICU admission were respiratory failure and shock/sepsis, each accounting for 34% of cases, while complications associated with oncological therapy accounted for less than 8%. The median age of hematological patients (n = 129) was 62 years (IQR 50-70), and for solid tumor patients (n = 38), it was 60 years (IQR 52-65). Predominant disease entities included lymphoma (43%) and acute myeloid leukemia (29%) among hematological patients, and lung cancer (47%) and gastrointestinal malignancies (17%) among solid tumor patients. Hematological patients had a significantly higher median Simplified Acute Physiology Score II (47 vs. 39 points; p=0.013), a higher need for invasive mechanical ventilation (59% vs. 50%; p=0.3), renal replacement therapy (54% vs. 24%; p < 0.001), and a higher 1-year mortality rate (64% vs. 53%; p=0.2) compared to solid tumor patients. The hazard ratio for 1 year survival for male sex was 2.34 (1.31-3.49), for mechanical ventilation 2.01 (1.33-3.04), for vasopressor therapy 1.98 (1.27-3.10), and for renal replacement therapy 1.51 (1.03-2.23), respectively. Administering intravenous chemotherapy in an ICU setting remains challenging, and the experience to establish an indication for systemic chemotherapy is still challenging. However, the study demonstrates that, after careful interdisciplinary decision-making, a substantial number of patients can benefit from it.

Особенности медико-социальной характеристики пациентов трудоспособного возраста с гипертонической болезнью.

Hypertension is the leading disease among diseases of the circulatory system in the Russian Federation and is not only an important medical, but also a socio-economic problem. The purpose of the study: to study the medical and social characteristics of patients of working age with hypertension. Materials and methods. A study was conducted of 247 patients aged 30 to 50 years with an established diagnosis of «Hypertension with predominant heart disease without (congestive) heart failure» (hereinafter referred to as hypertension – GB), attached to a territorial polyclinic. The results of the work. In the observed patients, the diagnosis of GB in most cases was established when contacting a medical organization, in every fourth patient during periodic medical examination, in every sixth during medical examination. The average age of patients was 42.4±5.4 years, more women than men, two thirds of patients with higher education and are satisfied with their financial situation, three quarters are satisfied with housing conditions, 71.8% of patients are married. Conclusion. According to the survey, the medical and social characteristics of patients with GB made it possible to form a socio-hygienic portrait of a patient with GB: most of the population is occupied by women, the average age is almost the same for both groups and is 42.4±5.4 years old, who mostly have higher education, are married, are satisfied with their financial situation, housing conditions and morally- the psychological climate in the family, however, 53.6% of patients have bad habits, 66.0% have an average and high cardiovascular risk. The scope of the results. The use of the analyzed medical and social characteristics of patients of working age with hypertension for the formulation of preventive measures.

Nanomaterial-based synergistic strategies for combating dental caries: progress and perspectives.

Dental caries, as the predominant global oral disease, remains a critical public health issue worldwide, particularly in socioeconomically disadvantaged communities. However, common caries prevention approaches (e.g., oral health education, mechanical plaque removal, and delivery of fluoride agents) are still insufficient for optimal caries management, and therefore, alternative regimens that can supplement existing strategies are highly warranted. Nanomaterials exhibit considerable potential in combating cariogenic pathogens and biofilms owing to their promising antimicrobial capacity, improved penetration into biofilms, targeted precision delivery, and versatile physicochemical properties. As unifunctional materials are limited in caries management, this review underscores the latest advancement in multifunctional anti-caries nanomaterials/nanomedicines. It highlights the cutting-edge materials developed or engineered to (i)incorporate diagnostic capabilities to prevent caries at an early stage, thus enhancing treatment efficiency, (ii) integrate mechanical "brushing" with anti-caries approaches to mechanochemically eradicate biofilms, (iii) exert antimicrobial/antibiofilm effects while preserving dental hard tissue. The current work also outlines future directions for optimizing nanosystems in the management of dental caries while emphasizing the need for innovative solutions to improve preventive and therapeutic efficacies.

Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy: Results From a Meta-Analysis of the Global SBMA Dataset.

Spinal and bulbar muscular atrophy (SBMA) is a rare, slowly progressive, and debilitating disease without effective treatments available. Lack of reliable biomarkers and sensitive outcome measures makes clinical research conduct challenging. The primary objective of this study was to identify clinically meaningful and statistically sensitive outcome measures enabling the evaluation of therapeutic interventions in late-stage clinical trials. This study was a meta-analysis of SBMA patient-level data from 6 observational studies conducted in Italy, South Korea, Denmark, United Kingdom, Japan, and United States. Patients with confirmed SBMA genetic diagnosis and differing severity were enrolled following individual site protocols. Routine assessments were performed longitudinally for approximately 3 years, including one or more clinical outcomes, such as SBMA functional rating scale (SBMAFRS), 6-minute walk test (6MWT), quantitative muscle testing (QMT), and Adult Myopathy Assessment Tool (AMAT). A modified scale, m-SBMAFRS, was derived by including only lower limb and trunk subscales having lower variability and larger effect size compared with the others. Changes from baseline at follow-up time points were calculated for all measures, and percent changes using random slope models were calculated to compare clinical measure performances. A survey conducted on 196 patients by the Coordination of Rare Diseases at Sanford (CoRDS), elucidating the impact of specific disease aspects on patients' lives, was also evaluated to corroborate these research outcomes. This global SBMA dataset analyzed data from 278 men (mean age = 59.7 ± 10.8 years, mean disease duration = 17.7 ± 11.9 years). Patients progressed on SBMAFRS (-4.7 ± 6.2 points after 38 months with 1-year standard response mean [SRM] = 0.6) and 6MWT (distance walked decreased by -53.2 ± 87.0 meters after 26 months with 1-year SRM = 0.5). These measures showed lower variability and larger effect size than AMAT and QMT (1-year SRM = 0.1 and -0.2, respectively) and confirmed SBMA linear progression across a range of disease stages. The m-SBMAFRS also showed a significant yearly decline of 0.9 ± 1.5 points (SRM = 0.6) and more consistent performance with less variability across clinical sites. The CoRDS survey confirmed the relevance of lower limb strength and mobility, which correlated with higher quality-of-life metrics and were reported by patients as predominant disease issues. We generated a comprehensive global SBMA dataset, enabling the identification of sensitive functional end points for clinical trials. Possible limitations relate to data collection nuances across sites that a single study protocol could override.

Diverse Phenotypes, Consistent Treatment: A Study of 30 997 South Asian and White Inflammatory Bowel Disease Patients Using the UK Inflammatory Bowel Disease BioResource.

Studies in the UK and North America have suggested a distinct disease profile in South Asians compared to that of White populations. Disparities in the medical and surgical management of IBD in minority ethnic groups (including Black Americans and Asians) in the US have been shown, while data from Europe, including the UK, have been lacking. This study sought to evaluate South Asian (SA) and White (WH) inflammatory bowel disease (IBD) phenotypes, and to explore treatment approach variations between these cohorts in the UK using the IBD BioResource database. Differences between WH and SA IBD patients were analysed using demographic, phenotypic and outcome data. Drug utilisation patterns and surgical outcomes were assessed in propensity score-matched (PSM) cohorts with multivariable logistic regression, Cox regression and Kaplan-Meier analysis. 30,997 eligible patients were included. UC was the predominant disease subtype in SA (p<0.001). SA were younger at diagnosis (p<0.001), had a male preponderance (p<0.001), and were less likely to have a smoking history at diagnosis. The SA CD phenotype differed from WH, with less ileal (SA 30.3%, WH 38.4%, p=0.008) and stricturing (SA 16.9%, WH 25.6%, p<0.001) disease, but more perianal disease (SA 38.5%, WH 32.2%, p=0.009). More SA UC patients had extensive disease (SA 41.7%, WH 34.1%, p<0.001). In PSM cohorts, comparing treatments, there were no differences in 5-aminosalicylate, corticosteroid, thiopurine, anti-TNF or vedolizumab use. Survival analysis in matched cohorts showed no difference in time to surgery (CD) or colectomy (UC), and SA ethnicity was not associated with a difference in risk of surgery/colectomy. Demographic and phenotypic differences exist between UK SA and WH IBD patients, highlighting distinct ethnicity-related variance, and the need for a research focus on under-represented populations. In comparing matched SA and WH patients, no disparity in medical and surgical IBD therapy in UK healthcare has been demonstrated: treatment is consistent regardless of ethnicity.

The Tick Microbiome: The "Other Bacterial Players" in Tick Biocontrol.

Hard ticks (family Ixodidae) are one of the most predominant arthropod disease vectors worldwide, second only to mosquitoes. In addition to harboring animal and human pathogens, ticks are known to carry a microbial community constituted of non-pathogenic organisms, which includes maternally inherited intracellular endosymbionts and other environmentally acquired extracellular microorganisms. These microbial communities, which include bacteria, viruses, protozoans, and fungi-with often commensal, mutualistic, or parasitic associations with the tick-comprise the tick microbiome, bacteria being the most studied community. Many bacterial taxa frequently reported in ticks include soil, plant, and animal-associated microbes, suggesting many are environmentally acquired, including members with known entomopathogenic potential, such as Bacillus thuringiensis, Bacillus spp., and Pseudomonas spp. It has been reported that microbial community composition can impact pathogen persistence, dissemination, and fitness in ticks. In the United States, Ixodes scapularis (northeast) and I. pacificus (west) are the predominant vectors of Borrelia burgdorferi, the causal agent of Lyme disease. Amblyomma americanum is another important tick vector in the U.S. and is becoming an increasing concern as it is the leading cause of alpha-gal syndrome (AGS, or red meat allergy). This condition is caused by tick bites containing the galactose alpha 1,3 galactose (alpha-gal) epitope in their saliva. In this paper, we present a summary of the tick microbiome, including the endosymbiotic bacteria and the environmentally acquired (here referred to as the non-endosymbiotic community). We will focus on the non-endosymbiotic bacteria from Ixodes spp. and Amblyomma americanum and discuss their potential for novel biocontrol strategies.

Recent Apprises on Predominant Disease and Disorders Detected in BAU Vet Clinic, Mymensingh, Bangladesh

The present study was accompanied at the Veterinary Teaching Hospital, BAU Mymensingh, since November 2023 to January 2024, to acknowledge the three months clinical study on animals. A total of 1765 clinical cases of which 427 goats, 211 cats, and 1127 cattle were examined. The clinical cases were divided into three groups: surgical, gynecological, obstetrical, and medicinal cases. In contrast with gynecological and obstetrical (cattle 3.82%, goats 7.26%, and cats 7.11%) and surgical (cattle 15.17%, goats 22.48%, and cats 19.91%) cases, the most significant percentage of cases were medicinal (cattle 81.01%, goats 69.79%, and cats 72.99%). Among the medicinal cases in cattle, parasite infestation most significant was (65.72%), than other infectious diseases (17.09%), general systemic (6.57%), and digestive disorders (3.83%). Additional cases counted like skin conditions (1.75%), respiratory disorders (1.64%), metabolic diseases (1.53%), eye disease (0.33%), urogenital disorders (0.55%), and musculoskeletal disorders (0.99%). In case of goats, general systemic diseases were maximum significant (24.16%), then parasitic diseases (21.14%), infectious diseases (20.13%), and digestive disorders (19.46%). Moreover, eye disease (5.37%), respiratory disorder (5.37%), skin conditions (2.68%), and musculoskeletal disorders (1.68%) were observed. In pet animals like cats infectious diseases were utmost significant (25.97%), compared to parasitic diseases (20.13%) and digestive disorders (19.48%). Additionally, skin diseases (11.69%), respiratory disorders (8.44%), eye disease (2.60%) and musculoskeletal disorders were (1.30%). The most prevalent gynecological and obstetric problems among the gynecological and obstetric cases were identified as repeat breeding (30.23%) in cattle, retained placenta (35.48%) in goats, and dystocia (60.00%) in cats. Hernia (26.32%) in cattle, Bone fracture (28.13%) in goats, and Bone fracture (23.81%) in cats were documented. In conclusion, the represented percentage of diseases was observed in BAU Vet Clinics and we hope that these data will support in the development strategies to regulate the most important diseases in the study area.

Desmoplakin Cardiomyopathy in Pediatric Patients: A Distinct, Underrecognized Cohort of Arrhythmogenic Cardiomyopathy.

DSP cardiomyopathy is a distinct subset of arrhythmogenic cardiomyopathy, reported primarily in adults, that has predominantly left ventricular involvement and features of myocarditis. Clinical characteristics, risk stratification, and management of pediatric patients with DSP variants are not well known. We sought to identify phenotypic features and prognosis of pediatric patients with DSP pathogenic or likely pathogenic variants. Multicenter, retrospective study of patients <21 years of age with DSP variants from 6 tertiary pediatric hospitals. Thirty-four patients, including 10 probands with clinical disease and 24 genotype-positive phenotype-negative patients, were included in the study. The majority of probands were initially diagnosed with myocarditis (50%) and had biventricular (60%) or left ventricular predominant (40%) disease. Chest pain was the most common symptom at presentation (30%), and all had troponin elevation. Probands with homozygous or compound heterozygous DSP variants were likely to present at an early age (<13 years) with symptoms of heart failure, severe biventricular involvement, and dermatologic abnormalities. Low-voltage QRS was the most prominent ECG abnormality. Of those who underwent implantable cardioverter defibrillator implantation, 50% received appropriate implantable cardioverter defibrillator therapy and were found to have significant biventricular involvement in addition to severe left ventricular dysfunction with an ejection fraction <35%. DSP cardiomyopathy in children and adolescents has varied phenotypic manifestations based on age and genotype and often can be diagnosed as myocarditis. Severe left ventricular dysfunction and biventricular involvement may be associated with a higher likelihood of malignant ventricular tachyarrhythmia.

Survival Dynamics of Invasive Fungal Diseases in Pediatric Hemato-Oncology Patients at a Tertiary Medical Facility in Mexico from July 2020 to July 2023

Abstract Background Invasive fungal diseases (IFD) have been increasing in prevalence over the past two decades, with filamentous fungi being the most common cause. However, candidiasis remains the predominant etiology of infection, especially in cases of neutropenic fever accompanied by neutropenic colitis. The prevalence of infections caused by Aspergillus species, Mucor species, Fusarium, and other species is higher among individuals with severe and extended neutropenia and those who have undergone hematopoietic progenitor cell transplantation. Methods A retrospective, descriptive, observational study was conducted to identify cases of patients diagnosed with invasive fungal diseases, categorizing them as possible, probable, or confirmed. In our comprehensive analysis of cases, we prioritize the examination of diseases induced by filamentous fungi, while considering the specific chemotherapy regimen administered and the particular oncological condition. Results The predominant etiology observed was invasive aspergillosis, followed by mucormycosis. A total of 18 cases suggestive of invasive Aspergillosis were identified, but clinical or histopathological investigations were not conducted due to limitations. The majority of cases were pulmonary, accounting for 92% of cases, while rhinosinusal involvement was identified in 8%. Factors such as clinical characteristics, imaging studies, serum galactomannan determination, and microbiological culture were considered. The patient survival rate was found to be 86.7%, with an average treatment duration of six weeks. A mortality rate of 3.7% was observed due to the underlying disease during the consolidation phase of invasive fungal diseases. Conclusion In our study, invasive aspergillosis emerged as the predominant invasive fungal disease in pediatric hemato-oncology patients. Despite challenges in conducting comprehensive investigations, our findings underscore the importance of timely diagnosis and management. The 86.7% survival rate reflects the efficacy of the treatment approach employed, while the observed mortality emphasizes the impact of underlying diseases on outcomes. This study contributes valuable insights to the understanding and improvement of survival dynamics in pediatric patients facing invasive fungal diseases.

Exploring the mechanisms of Cornus officinalis in the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking and molecular dynamics simulations

Non-alcoholic steatohepatitis (NASH) is a predominant metabolic liver disease, typically characterized by hepatic steatosis, oxidative stress, and inflammation. The traditional Chinese medicine Cornus officinalis possesses anti-inflammatory and hepatoprotective pharmacological properties and has shown ameliorative effects on NASH. however, its mechanism of action remains unclear. This study aims to elucidate the mechanisms by which C. officinalis ameliorates NASH. The active components of C. officinalis were analyzed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the corresponding targets were predicted. Subsequently, the DisGeNET, GeneCards, and GEO databases were employed to identify NASH-related targets. Venn diagrams were used to intersect the C. officinalis targets with the NASH targets. Protein–protein interaction (PPI) networks were constructed using the STRING database, and PPI network analysis was performed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), followed by molecular docking validation. Cornus officinalis was found to contain 20 major active ingredients corresponding to 672 potential targets, 61 of which overlapped with NASH targets. PPI network, GO, and KEGG pathway analyses identified four targets with the highest correlation, and molecular docking results indicated that the active ingredients of C. officinalis exhibited strong binding affinities to NASH targets. The treatment of NASH with C. officinalis is characterized by multiple active ingredients and multiple targets, underscoring the major advantage of traditional Chinese medicine in treating NASH.

Microbiology of Actinomyces Species Isolated From Patients With Invasive Disease and Contaminated Samples in a Comprehensive Cancer Center.

Actinomyces are mucous membrane commensals that infrequently cause invasive disease. Our goal was to define Actinomyces species prevalence, the predominant disease site and risk factors for actinomycosis. We retrospectively reviewed patients with growth of Actinomyces species from cultures in a single-cancer center from July 2007 to June 2020. Proven invasive actinomycosis was defined as the presence of compatible clinical syndrome and radiographic findings with histopathological confirmation or culture from a normally sterile site. Probable invasive actinomycosis was defined based on the same criteria but without histologic confirmation. Contaminants were defined as culture growth in the absence of clinical or radiological findings consistent with disease. Speciation of Actinomyces was performed by the bioMerieux VITEK 2 anaerobic and coryneform identification card. Of 235 patients, 179 (76.2%) had malignancy. Among 90 (38.3%) patients with invasive actinomycosis, A odontolyticus was isolated in 32 (35.6%), followed by A meyeri in 20 (22.2%), and A naeslundii in 17 (18.9%). Among 145 (61.7%) colonized patients, A odontolyticus was isolated in 67 (46.2%), followed by A naeslundii in 27 (18.6%). Abdominopelvic infection was the most common site for invasive actinomycosis documented in 54 patients (60.0%) followed by orocervicofacial in 14 (15.6%) and thoracic in 10 (11.1%). A odontolyticus, A meyeri, and A naeslundi were the most frequently isolated species causing invasive actinomycosis, and A odontolyticus and A nauslendii among colonizers. Abdominopelvic represented the most frequent site for invasive disease. Further studies are needed to investigate the epidemiology of Actinomyces species in this population.

STING Promotes the Progression of ADPKD by Regulating Mitochondrial Function, Inflammation, Fibrosis, and Apoptosis.

Autosomal dominant polycystic kidney disease (ADPKD) is a predominant genetic disease, which is caused by mutations in PKD genes and is associated with DNA damage in cystic cells. The intrinsic stimulator of interferon genes (STING) pathway is crucial for recognizing damaged DNA in the cytosol, triggering the expression of inflammatory cytokines to activate defense mechanisms. However, the precise roles and mechanisms of STING in ADPKD remain elusive. In this study, we show that Pkd1 mutant mouse kidneys show upregulation of STING, which is stimulated by the DNAs of nuclear and mitochondrial origin. The activation of STING promotes cyst growth through increasing (1) the activation of NF-κB in Pkd1 mutant cells and (2) the recruitment of macrophages in the interstitial and peri-cystic regions in Pkd1 mutant mouse kidneys via NF-κB mediating the upregulation of TNF-α and MCP-1. Targeting STING with its specific inhibitor C-176 delays cyst growth in an early-stage aggressive Pkd1 conditional knockout mouse model and a milder long-lasting Pkd1 mutant mouse model. Targeting STING normalizes mitochondrial structure and function, decreases the formation of micronuclei, induces Pkd1 mutant renal epithelial cell death via p53 signaling, and decreases renal fibrosis in Pkd1 mutant mouse kidneys. These results support that STING is a novel therapeutic target for ADPKD treatment.

Biological Barriers for Drug Delivery and Development of Innovative Therapeutic Approaches in HIV, Pancreatic Cancer, and Hemophilia A/B.

Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease's pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which-upon effective drug delivery to their target cells-allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease.

Efficacy of Pomegranate Peel Extract Mouthwash on Gingivitis and C-reactive protein

Background and objective: Gingivitis is characterized as the world’s most predominant inflammatory periodontal disease. Healthy mouth and teeth are obtained by brushing and uses mouthwash. And because of the side effects of chlorhexidine, pomegranate peel extract mouthwash used alternative which are thought to have anti-inflammatory effect. The aim of this study is to prepare a herbal mouthwash and to evaluate the efficacy of pomegranate peel extract mouthwash on plaque index, gingival index, and C-reactive protein on moderate gingivitis patients. Method: this study is a clinical crossover design study, which consists of 25 volunteers with moderate gingivitis, who visited Duhok Dental Training Center. This study started from December 2022 to March 2023. Plaque and gingival index with a sample of saliva for C-reactive protein measuring were taken as a baseline before each mouth wash and after that, the pomegranate peel extract mouthwash was used for two weeks, then three weeks wash out between them, then chlorhexidine mouth wash was used for two weeks (crossover method). All saliva samples were analyzed using (CRP ELISA Test). Results: Twenty-five patients who used pomegranate peel extract mouthwash showed a significant reduction after two weeks used (CRP=162.28, GI=0.54, PI=0.82) and p value (&lt;0.0001) in mean C-reactive protein, gingival index, and plaque index from baseline which was (CRP=669.78, GI=1.88, PI=2.11). Conclusion: Pomegranate peel extract mouthwash had been shown effective against moderate gingivitis in adult patients with no systemic diseases through lowering in mean salivary C-reactive protein, gingival index, and plaque index.

Identification of factors directly linked to incident chronic obstructive pulmonary disease: A causal graph modeling study.

Beyond exposure to cigarette smoking and aging, the factors that influence lung function decline to incident chronic obstructive pulmonary disease (COPD) remain unclear. Advancements have been made in categorizing COPD into emphysema and airway predominant disease subtypes; however, predicting which healthy individuals will progress to COPD is difficult because they can exhibit profoundly different disease trajectories despite similar initial risk factors. This study aimed to identify clinical, genetic, and radiological features that are directly linked-and subsequently predict-abnormal lung function. We employed graph modeling on 2,643 COPDGene participants (aged 45 to 80 years, 51.25% female, 35.1% African Americans; enrollment 11/2007-4/2011) with smoking history but normal spirometry at study enrollment to identify variables that are directly linked to future lung function abnormalities. We developed logistic regression and random forest predictive models for distinguishing individuals who maintain lung function from those who decline. Of the 131 variables analyzed, 6 were identified as informative to future lung function abnormalities, namely forced expiratory flow in the middle range (FEF25-75%), average lung wall thickness in a 10 mm radius (Pi10), severe emphysema, age, sex, and height. We investigated whether these features predict individuals leaving GOLD 0 status (normal spirometry according to Global Initiative for Obstructive Lung Disease (GOLD) criteria). Linear models, trained with these features, were quite predictive (area under receiver operator characteristic curve or AUROC = 0.75). Random forest predictors performed similarly to logistic regression (AUROC = 0.7), indicating that no significant nonlinear effects were present. The results were externally validated on 150 participants from Specialized Center for Clinically Oriented Research (SCCOR) cohort (aged 45 to 80 years, 52.7% female, 4.7% African Americans; enrollment: 7/2007-12/2012) (AUROC = 0.89). The main limitation of longitudinal studies with 5- and 10-year follow-up is the introduction of mortality bias that disproportionately affects the more severe cases. However, our study focused on spirometrically normal individuals, who have a lower mortality rate. Another limitation is the use of strict criteria to define spirometrically normal individuals, which was unavoidable when studying factors associated with changes in normalized forced expiratory volume in 1 s (FEV1%predicted) or the ratio of FEV1/FVC (forced vital capacity). This study took an agnostic approach to identify which baseline measurements differentiate and predict the early stages of lung function decline in individuals with previous smoking history. Our analysis suggests that emphysema affects obstruction onset, while airway predominant pathology may play a more important role in future FEV1 (%predicted) decline without obstruction, and FEF25-75% may affect both.

Microbial and Inflammatory Salivary Biomarkers of Periodontal Diseases

Recent data reveals that severe periodontal diseases affect approximately 19% of global adult populations, impacting more than 1 billion individuals universally, ranking it as the sixth most predominant human disease. Diagnosis and treatment plans for periodontal disease entirely depend solely on the assessment of traditional clinical parameters. However, these parameters are not sensitive and are subject to error. Hence, microbial and inflammatory biomarkers of periodontal diseases in saliva have attracted of interest. This review aims to evaluate the salivary components as potential diagnostic tools for periodontal diseases. In addition to periodontal pathogens, interest in salivary biomarkers of periodontal disease is increasing, and a number of biomarkers have the potential to be accurate indicators of disease and the effectiveness of therapy. The most up to date studies examining the microbial and inflammatory biomarkers with both diagnostic and prognostic values in saliva were reviewed for the purpose of this study. It is apparent that saliva has many advantages over other oral fluids such gingival crevicular fluid and mouth rinse as a tool for diagnosis of periodontal disease. Biomarkers can identify and quantify periodontal risk through objective measures. Further, the combination of biomarkers seems to enhance the diagnostic and prognostic value of the biomarkers. Amongst the microbial biomarkers of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Tannerella forsythia are widely used with some promising results. Whereas, the inflammatory salivary biomarkers of IL-1β and MMP-8 are widely used for diagnosing periodontitis and predicting the future treatment outcome.

Clinical Features and Characteristics of Hand, Foot, and Mouth Disease Caused by Recent Coxsackievirus A6: Five Cases in Japan from 2019 to 2022.

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enteroviruses. Coxsackievirus A6 (CV-A6)-associated HFMD has recently emerged as a predominant disease worldwide. Here, we describe five HFMD cases caused by CV-A6 in Japan from 2019 to 2022. All clinical courses were not severe and were self-limited, and the skin exanthema with vesicles differed from that in classical HFMD. Phylogenetic analysis showed that the major epidemic strain cluster of CV-A6 was formed independently in 2011, and our latest CV-A6 strains in Japan were detected within this cluster. The five cases described in this report indicate the recent shift in the predominant and continuous disease manifestation of CV-A6-associated HFMD.