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The American Journal of Psychiatry Jul 2024
Topics: Humans; Multifactorial Inheritance; Phenotype; Mental Disorders; Genome-Wide Association Study; Genetic Predisposition to Disease
PubMed: 38946280
DOI: 10.1176/appi.ajp.20240398 -
Acta Dermatovenerologica Croatica : ADC Mar 2024The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory...
BACKGROUND
The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory illnesses, such as psoriasis, is explored herein. We examined the link between resistin gene polymorphisms (-420 C>G and +299 G>A) and psoriasis in the Turkish population.
METHODS
In this study, we examined 107 patients with psoriasis and 103 healthy controls. Resistin -420 C>G (rs1862513) and +299 G>A (rs3745367) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTS
In patients with psoriasis, the frequency of the resistin -420 CG genotype was meaningfully lower than in the controls. In comparison with the controls, the resistin +299 GA genotype and A allele frequencies were significantly higher. The Resistin -420 CG genotype significantly reduced the risk of psoriasis incidence, while the resistin +299 GA genotype and A allele were found to be associated with a higher risk of psoriasis.
CONCLUSIONS
In the Turkish community, resistin gene polymorphisms at -420 C>G and +299 G>A may exert an important influence on psoriasis etiology and susceptibility.
Topics: Humans; Psoriasis; Resistin; Male; Female; Adult; Middle Aged; Genetic Predisposition to Disease; Turkey; Case-Control Studies; Genotype; Promoter Regions, Genetic; Gene Frequency; Polymorphism, Genetic; Polymorphism, Single Nucleotide
PubMed: 38946181
DOI: No ID Found -
Experimental Eye Research Jun 2024Aging changes the responsiveness of our immune defense, and this decline in immune reactivity plays an important role in the increased susceptibility to infections that...
Aging changes the responsiveness of our immune defense, and this decline in immune reactivity plays an important role in the increased susceptibility to infections that marks progressing age. Aging is also the most pronounced risk factor for development of age-related macular degeneration (AMD), a disease that is characterized by dysfunctional retinal pigment epithelial (RPE) cells and loss of central vision. We have previously shown that acute systemic viral infection has a large impact on the retina in young mice, leading to upregulation of chemokines in the RPE/choroid (RPE/c) and influx of CD8 T cells in the neuroretina. In this study, we sought to investigate the impact of systemic infection on the RPE/c in aged mice to evaluate whether infection in old age could play a role in the pathogenesis of AMD. We found that systemic infection in mice led to upregulation of genes from the crystallin family in the RPE/c from aged mice, but not in the RPE/c from young mice. Crystallin alpha A (CRYAA) was the most upregulated gene, and increased amounts of CRYAA protein were also detected in the aged RPE/c. Increased CRYAA gene and protein expression has previously been found in drusen and choroid from AMD patients, and this protein has also been linked to neovascularization. Since both drusen and neovascularization are important hallmarks of advanced AMD, it is interesting to speculate if upregulation of crystallins in response to infection in old age could be relevant for the pathogenesis of AMD.
PubMed: 38945517
DOI: 10.1016/j.exer.2024.109984 -
Reproductive Toxicology (Elmsford, N.Y.) Jun 2024In utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life....
In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFβ/ROS/Akt signaling pathway.
BACKGROUND
In utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life. However, the underlying molecular mechanisms remain largely unknown. We tested the hypothesis that fetal nicotine aerosol exposure reprograms ischemia-sensitive gene expressions, resulting in increased heart susceptibility to ischemic injury and cardiac dysfunction in adulthood.
METHODS
Pregnant rats were exposed to chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21. Experiments were performed on 6-month-old adult offspring.
RESULTS
CINA exposure increased ischemia-induced cardiac injury and cardiac dysfunction compared to the control group, which was associated with over- expression of angiotensin II receptor (ATR) protein in the left ventricle (LV) of adult offspring. Meanwhile, CINA exposure up-regulated cardiac TGF-β/SMADs family proteins in the LV. In addition, CINA exposure enhanced cardiac reactive oxygen species (ROS) production and increased the DNA methylation level. The levels of phosphorylated-Akt were upregulated but LC3B-II/I protein abundances were downregulated in the hearts isolated from the CINA-treated group.
CONCLUSION
Fetal nicotine aerosol exposure leads to cardiac dysfunction in response to ischemic stimulation in adulthood. Two molecular pathways are implicated. First, fetal CINA exposure elevates cardiac ATR levels, affecting the TGFβ-SMADs pathway. Second, heightened Angiotensin II/ATR signaling triggers ROS production, leading to DNA hypermethylation, p-Akt activation, and autophagy deficiency. These molecular shifts in cardiomyocytes result in the development of a heart ischemia-sensitive phenotype and subsequent dysfunction in adult offspring.
PubMed: 38945500
DOI: 10.1016/j.reprotox.2024.108650 -
Chemosphere Jun 2024As the most widely employed artificial nanomaterials, silver nanoparticles (AgNPs) have been implicated in oxidative stress-induced liver injury. Despite these...
As the most widely employed artificial nanomaterials, silver nanoparticles (AgNPs) have been implicated in oxidative stress-induced liver injury. Despite these observations, the precise mechanisms underpinning AgNPs-induced hepatotoxicity have yet to be fully elucidated. This study embarked on an intersectional analysis of the GEO dataset (GSE139560), which encompassed murine liver tissues subjected to AgNPs, alongside datasets related to ferroptosis. Through this approach, three pivotal ferroptosis-associated genes (Arrdc3, Txnip, and Egfr) were identified. Further integration with disease model analysis from GSE111407 and GSE183158 unveiled a significant association between AgNPs exposure and alterations in glucose metabolism and insulin signaling pathways, intricately linked with the identified key ferroptosis genes. This correlation fostered the hypothesis that ferroptosis significantly contributed to the hepatotoxicity triggered by AgNPs. Subsequent Gene Set Enrichment Analysis (GSEA) pointed to the activation of ferroptosis-associated pathways, specifically MAPK and PPAR, under AgNPs exposure. Examination of the mRNA-miRNA interaction network revealed co-regulated upstream miRNAs targeting these pivotal genes, establishing a nexus to ferroptosis and heightened liver susceptibility. Experimental validation employing an adult zebrafish model exposed to AgNPs from 90 to 120 dpf demonstrated elevated levels of Fe and MDA in the zebrafish livers, along with conspicuous mitochondrial morphological alterations, thereby reinforcing the notion that AgNPs precipitate liver dysfunction predominantly through the induction of ferroptosis. These insights collectively underscore the role of ferroptosis in mediating the adverse effects of AgNPs on liver glucose metabolism and insulin sensitivity, culminating in liver dysfunction. Overall, these results enhance the understanding of nanomaterial-induced hepatotoxicity and inform strategies to mitigate such health risks.
PubMed: 38945227
DOI: 10.1016/j.chemosphere.2024.142673 -
Biomaterials Jun 2024We present a bioprinted three-layered airway model with a physiologically relevant microstructure for the study of severe acute respiratory syndrome coronavirus 2...
We present a bioprinted three-layered airway model with a physiologically relevant microstructure for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection dynamics. This model exhibited clear cell-cell junctions and mucus secretion with an efficient expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Having infected air-exposed epithelial cells in the upper layer with a minimum multiplicity of infection of 0.01, the airway model showed a marked susceptibility to SARS-CoV-2 within one-day post-infection (dpi). Furthermore, the unique longevity allowed the observation of cytopathic effects and barrier degradation for 21 dpi. The in-depth transcriptomic analysis revealed dramatic changes in gene expression affecting the infection pathway, viral proliferation, and host immune response which are consistent with COVID-19 patient data. Finally, the treatment of antiviral agents, such as remdesivir and molnupiravir, through the culture medium underlying the endothelium resulted in a marked inhibition of viral replication within the epithelium. The bioprinted airway model can be used as a manufacturable physiological platform to study disease pathogeneses and drug efficacy.
PubMed: 38944967
DOI: 10.1016/j.biomaterials.2024.122689 -
Journal of Gastrointestinal and Liver... Jun 2024Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral...
BACKGROUND AND AIMS
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
MATERIALS
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Topics: Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Lipase; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Middle Aged; 17-Hydroxysteroid Dehydrogenases; Genetic Predisposition to Disease; Case-Control Studies; Hepatitis B, Chronic; Prognosis; Adult; Turkey; Risk Factors; Prospective Studies; Phenotype; Genetic Association Studies; Acyltransferases; Phospholipases A2, Calcium-Independent
PubMed: 38944871
DOI: 10.15403/jgld-5474 -
Mymensingh Medical Journal : MMJ Jul 2024Very early onset inflammatory bowel disease (VEO-IBD) is called when age of onset of IBD occurs below 6 years. Though it is rare, it has been increasing over last decade... (Review)
Review
Very early onset inflammatory bowel disease (VEO-IBD) is called when age of onset of IBD occurs below 6 years. Though it is rare, it has been increasing over last decade with decreasing age of onset. VEO-IBD is different compared with pediatric and adult-onset IBD in many aspects, including the disease type, location of the lesion, disease behavior and genetic susceptibility. These children with VEO-IBD are usually present with more severe disease than older children and adults. VEO-IBD is associated with monogenic defect. The thought of a monogenic cause of VEO-IBD was first confirmed by the detection of mutations of interleukin 10 (IL-10) receptor genes that cause impaired IL-10 signaling. Monogenic IBD possesses significant concern because it usually presents with refractory to conventional IBD treatment or fistulous Crohn's disease, so early treatment with biologics or an alternative approach such as hematopoietic stem cell transplantation (HSCT) might be looked-for. Before establishing IBD, we must think of more common diseases of this age group. Infection and Cow's milk protein allergy (CMPA) are two common conditions and it can cause severe colitis. Confirmation of chronic intestinal inflammation by endoscopies is of greatest significance for the diagnosis of IBD. There should be no age limit for performing endoscopies. Severe disease should be treated with biologic agents and surgery. Identification of genes associated with IBD leads to better understanding of its pathogenesis, which could help to provide more targeted interventions. We discuss the topic here to create awareness among Pediatricians so that the patients can be benefited.
Topics: Humans; Inflammatory Bowel Diseases; Age of Onset; Child; Child, Preschool
PubMed: 38944746
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024Autoimmune thyroiditis gradually destroys the thyroid gland leading to hypothyroidism and may even lead to papillary thyroid carcinoma. Deficiency of Vitamin D has been...
Autoimmune thyroiditis gradually destroys the thyroid gland leading to hypothyroidism and may even lead to papillary thyroid carcinoma. Deficiency of Vitamin D has been linked to development of autoimmunity. Single nucleotide polymorphisms of the Vitamin D receptor gene have associated with autoimmune diseases in several studies. In this hospital based non interventional cross-sectional study Vitamin D receptor gene was studied for FokI (rs2228570) polymorphism from purified DNA in forty-eight adult cases and fifty age and sex matched healthy controls. This study was conducted in the department of Biochemistry, Calcutta National Medical College, Kolkata, West Bengal, India from January 2021 to July 2022. Their DNA was isolated using phenol chloroform method and were analysed for the related single nucleotide polymorphism by restriction digestion using appropriate restriction enzymes after amplification by PCR. Differences in allele frequencies between two groups were estimated by chi square and odds ratio test. Any potential association between the vitamin D anti TPO antibody and thyroid hormone status with polymorphic variations were assessed by post hoc ANOVA among the three genotypes. The distribution of FF genotype was significantly higher among the case group (Χ²=10.2788, p=0.006). The odds ratio for the allele F was significantly higher in case group for a range of 1.97 to 5.94 for 95 percent confidence interval (Χ²=13.9678, p=<0.001). The genotype FF group had significantly lowest Vitamin D (p=0.008) and highest Anti TPO ab (p=0.031) compared to Ff and ff genotypes. Thus, significant association was revealed between the VDR gene Fok1(rs2228570) polymorphism and autoimmune thyroiditis with the predominance of FF genotype being a strong susceptibility factor for autoimmune thyroiditis and Vitamin D deficiency in the studied population of Eastern India.
Topics: Humans; Receptors, Calcitriol; Thyroiditis, Autoimmune; Male; Female; Adult; Vitamin D; Polymorphism, Single Nucleotide; Cross-Sectional Studies; Case-Control Studies; Middle Aged; India; Genetic Predisposition to Disease; Gene Frequency; Genotype
PubMed: 38944740
DOI: No ID Found -
The Science of the Total Environment Jun 2024Microplastics (MPs) are particles with sizes of ≤5 mm formed when plastic materials break down. These contaminants are often found in marine environments, making it... (Review)
Review
Microplastics (MPs) are particles with sizes of ≤5 mm formed when plastic materials break down. These contaminants are often found in marine environments, making it easy for sea turtles to ingest them and for their microbiome to be exposed. MPs can disrupt microbiome balance, leading to dysbiosis and making organisms more susceptible to diseases. Owing to the significance of these processes, it is crucial to dedicate research to studying the metabolic and genetic analysis of the gut microbiome in sea turtles. The objective of this study was to describe the effects of exposure to MPs on the gut microbiome of sea turtles, based on current knowledge. This review also aimed to explore the potential link between MP exposure and disease susceptibility in these animals. We show that the metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFAs), polyamines, and polysaccharide A, can regulate the expression of host genes. Regulation occurs through various mechanisms, including histone acetylation, DNA methylation, and the modulation of cytokine gene expression. These processes are essential for preserving the integrity of the gut mucosa and enhancing the functionality of immune cells. Exposure to MPs disrupts the gut microbiome and alters gene expression, leading to immune system disturbances in sea turtles. This vulnerability makes turtles more susceptible to opportunistic microorganisms such as chelonid alphaherpesvirus 5 (ChAHV5), which is linked to the development of fibropapillomatosis (FP). Additionally, targeted dietary interventions or the use of live microorganisms such as probiotics can help restore microbial biodiversity and recover lost metabolic pathways. The goal of these interventions is to restore the functionality of the immune system in sea turtles undergoing rehabilitation at specialized centers. The gut microbiome plays a crucial role in sea turtle health, sparking discussions and investigations that can potentially lead to promising treatments for these animals.
PubMed: 38944299
DOI: 10.1016/j.scitotenv.2024.174298