Occurrence Of Disease Research Articles

Hydrogen Sulfide in Musculoskeletal Diseases: Molecular Mechanisms and Therapeutic Opportunities.

Significance: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H2S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential therapeutic significance for these diseases. Recent Advances: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, muscle contraction under high fever, arthritis, and disc herniation, can be alleviated by treatment with H2S. H2S may be conducive to the development of multiple myeloma. The mechanism of action of H2S in the musculoskeletal system has been partly elucidated. A variety of H2S donors and nano-delivery systems provide promising prospects for H2S-based therapies. Critical Issues: Related research remains at the level of cell or animal experiments, but clinical research is lacking. The roles of H2S in more musculoskeletal disorders remain largely unknown. The serious consequences of musculoskeletal diseases have not been widely concerned. Targeted delivery of H2S remains a challenging task in musculoskeletal diseases. Future Directions: Develop therapeutic drugs for musculoskeletal diseases based on H2S and test their safety, efficacy, and tolerance. Explore the combination of current drugs for musculoskeletal diseases with H2S-releasing components to improve the therapeutic efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use. Antioxid. Redox Signal. 00, 000-000.

Implementation of an Automated System Using Machine Learning Models to Accelerate the Process of In Silico Identification of Small Molecules As Drug Candidates.

Drugs are commonly utilized to diagnose, cure, or prevent the occurrence of diseases, as well as to restore, alter, or change organic functions. Drug discovery is a time-consuming, costly, difficult, and inefficient process that yields very few medicinal breakthroughs. Drug research and design involves the capturing of structural information for biological targets and small molecules as well as various in silico methods, such as molecular docking and molecular dynamic simulation. This article proposes the idea of expediting computational drug development through a collaboration of scientists and universities, similar to the Human Genome Project using machine learning (ML) strategies. We envision an automated system where readily available or novel small molecules (chemical or plant-derived), as well as their biological targets, are uploaded to an online database, which is constantly updated. For this system to function, machine learning strategies have to be implemented, and high-quality datasets and high quality assurance of the ML models will be required. ML can be applied to all computational drug discovery fields, including hit discovery, target validation, lead optimization, drug repurposing, and data mining of small compounds and biomolecule structures. Researchers from various disciplines, such as bioengineers, bioinformaticians, geneticists, chemists, computer and software engineers, and pharmacists, are expected to collaborate to establish a solid workflow and certain parameters as well as constraints for a successful outcome. This automated system may help speed up the drug discovery process while also lowering the number of unsuccessful drug candidates. Additionally, this system will decrease the workload, especially in computational studies, and expedite the process of drug design. As a result, a drug may be manufactured in a relatively short time.

Global A-to-I RNA editing during myogenic differentiation of goat MuSCs.

RNA editing, especially A-to-I editing sites, is a common RNA modification critical for stem cell differentiation, muscle development, and disease occurrence. Unveiling comprehensive RNA A-to-I editing events associated with myogenesis of the skeletal muscle satellite cells (MuSCs) is essential for extending our knowledge of the mechanism underpinning muscle development. A total of 9,632 RNA editing sites (RESs) were screened in the myoblasts (GM), myocytes (DM1), and myotubes (DM5) samples. Among these sites, 4,559 A-to-I edits were classified and further analyzed. There were 3,266 A-to-I sites in the protein-coding region, out of which 113 missense sites recoded protein. Notably, five A-to-I sites in the 3' UTR of four genes (TRAF6, NALF1, SLC38A1, ENSCHIG00000019092) altered their targeted miRNAs. Furthermore, a total of 370 A-to-I sites with different editing levels were detected, including FBN1, MYH10, GSK3B, CSNK1D, and PRKACB genes. These genes were predominantly enriched in the cytoskeleton in muscle cells, the hippo signaling pathway, and the tight junction. Furthermore, we identified 14 hub genes (TUFM, GSK3B, JAK2, RPSA, YARS1, CDH2, PRKACB, RUNX1, NOTCH2, CDC23, VCP, FBN1, RARS1, MEF2C) that potentially related to muscle development. Additionally, 123 stage-specific A-to-I editing sites were identified, with 43 sites in GM, 25 in DM1, and 55 in DM5 samples. These stage-specific edited genes significantly enriched essential biological pathways, including the cell cycle, oocyte meiosis, motor proteins, and hedgehog signaling pathway. We systematically identified the RNA editing events in proliferating and differentiating goat MuSCs, which was crucial for expanding our understanding of the regulatory mechanisms of muscle development.

Evaluation relationship between VDR gene and clinical and inflammatory factors in patients with RRMS.

Adipocyte levels including leptin and FABS-4 levels, adiponectin, obesity, and vitamin D can be related to the occurrence and exacerbation of MS disease. This research aimed at determining the relationship between VDR gene changes and clinical and inflammatory factors in patients with relapsing-remitting multiple sclerosis (RRMS). This case/control study was conducted based on the ethical principles of Helsinki. RRMS disease was confirmed based on history, clinical signs, radiological signs, and neurologist's diagnosis. The research population consisted of healthy people and patients with RRMS referring to Hazrat Rasool Akram Hospital between 2021 and 2023 who met the criteria for entering the research. FokI polymorphism is associated with a substantial increase in risk, with an odds ratio of 7.28, for those with the FF genotype who have RRMS compared to healthy individuals (OR=7.28: 95% CI; 1.86, 28.41). The presence of FokI polymorphism significantly raises the likelihood of developing RRMS in persons with the FF genotype compared to healthy individuals, with an odds ratio of 28.7. RRMS patients with genotypes did not exhibit a significant increase in risk compared to controls for FokI, ApaI, TaqI, and BsmI polymorphisms. None of the studied polymorphisms revealed a significant risk in obese patients with different genotypes compared to the obese people. Further research, including more cases, is needed to avoid results that could be inflated by small samples or low frequencies of minor alleles.

Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients'suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Biological characterization and in vitro fungicide screening of a new causal agent of walnut leaf spot in Guizhou Province, China.

Walnut (Juglans regia L.) is a widely grown nut plant worldwide, including in Guizhou Province, located in southwest China. The high quality and special taste make Guizhou walnuts, particularly those produced in Hezhang County, a "Chinese National Geographical Indication Product" that substantially contributes to the local economy and grower's income. In July 2022, a serious occurrence of leaf spot disease was observed in a walnut plantation area, Shuitang Town, Hezhang County, Guizhou Province, China (27°07'67″N, 104°64'61″E). The causal agent was identified as Didymella segeticola through morphological characterization and amplification and sequencing of the internal transcribed spacer (ITS) region, beta-tubulin (TUB) gene, and glyceraldehyde-3-phosphate dehydrogenase (G3PD) gene. Koch's postulates, including re-isolation and identification, were performed to confirm its pathogenicity on healthy leaves. To our knowledge, this is the first report of D. segeticola causing leaf spot on walnuts worldwide. Further, to determine its biological characteristics, which could be utilized for future disease management, the effects of temperature, light, and carbon and nitrogen resources on mycelial growth, conidia production, and conidia germination and the effects of humidity on conidia germination were studied. The optimum temperature for mycelial growth of representative strain D. segeticola C27 was 20°C. Increasing the light period significantly decreased conidia production and conidia germination. Maltose and beef extract were the best carbon and nitrogen sources, respectively, for the pathogen. Conidia germination was enhanced at 90% humidity. In vitro screening of effective fungicides was conducted. Among the 20 screened fungicides, difenoconazole showed the best inhibition rate, with an EC50 (concentration for 50% of the maximal effect) of 0.0007 μg/mL. Tetramycin also showed sufficient inhibitory effects against D. segeticola, with an EC50 value of 0.0009 μg/mL. Our study provides new insights into the causal agent of walnut leaf spot in Guizhou, China, as well as the first pathogen characteristics and promising candidate fungicides for its management.

Multiple roles of mitochondrial autophagy receptor FUNDC1 in mitochondrial events and kidney disease.

This article reviews the latest research progress on the role of mitochondrial autophagy receptor FUN14 domain containing 1 (FUNDC1) in mitochondrial events and kidney disease. FUNDC1 is a protein located in the outer membrane of mitochondria, which maintains the function and quality of mitochondria by regulating mitochondrial autophagy, that is, the selective degradation process of mitochondria. The structural characteristics of FUNDC1 enable it to respond to intracellular signal changes and regulate the activity of mitochondrial autophagy through phosphorylation and dephosphorylation. During phosphorylation, unc-51-like kinase 1 (ULK1) promotes the activation of mitophagy by phosphorylating Ser17 of FUNDC1. In contrast, Src and CK2 kinases inhibit the interaction between FUNDC1 and LC3 by phosphorylating Tyr18 and Ser13, thereby inhibiting mitophagy. During dephosphorylation, PGAM5 phosphatase enhances the interaction between FUNDC1 and LC3 by dephosphorylating Ser13, thereby activating mitophagy. BCL2L1 inhibits the activity of PGAM5 by interacting with PGAM5, thereby preventing the dephosphorylation of FUNDC1 and inhibiting mitophagy. FUNDC1 plays an important role in mitochondrial events, participating in mitochondrial fission, maintaining the homeostasis of iron and proteins in mitochondrial matrix, and mediating crosstalk between mitochondria, endoplasmic reticulum and lysosomes, which have important effects on cell energy metabolism and programmed death. In the aspect of kidney disease, the abnormal function of FUNDC1 is closely related to the occurrence and development of many diseases. In acute kidney injury (AKI), cardiorenal syndrome (CRS), diabetic nephropathy (DN), chronic kidney disease (CKD) ,renal fibrosis (RF) and renal anemia, FUNDC1-mediated imbalance of mitophagy may be one of the key factors in disease progression. Therefore, in-depth study of the regulatory mechanism and function of FUNDC1 is of great significance for understanding the pathogenesis of renal disease and developing new treatment strategies.

Development of a chemiluminescent immunoassay based on magnetic solid phase for quantification of homocysteine in human serum

BackgroundHomocysteine (HCY) is a sulfur-containing amino acid that is an independent or important risk factor for the occurrence of many chronic diseases and is one of the most important indicators for determining health risks. However, existing HCY detection methods do not meet the requirements of clinical diagnosis. Therefore, there is an urgent need to establish new detection methods to meet the needs of clinical detection.ResultsIn this study, we used the principle of competitive method to establish a new method for the determination of HCY in human serum using a chemiluminescent enzyme immunoassay in conjunction with a chemiluminescent assay instrument that uses magnetic microparticles as the solid phase of the immunoreaction. The established method achieved satisfactory results in terms of minimum detection limit, specificity, accuracy, and clinical application. The limit of detection was 0.03 ng/mL. The intra-assay coefficient of variation (CV) was 1.94–5.05%, the inter-assay CV was 2.29–6.88%, and the recovery rate was 88.60–93.27%. Cross-reactivity with L-cysteine ranged from 0.0100 to 0.0200 μmol/L, and cross-reactivity with glutathione ranged from 0.0100 to 0.200 μmol/L, all of which were less than the limit of detection (LoD) of this method. The linear factor R of this method was greater than 0.99.ConclusionsIn summary, the developed method showed a good correlation with the product from Abbott. A total of 996 clinical patients with cardiovascular diseases were evaluated using the method developed in this study.

Untargeted Metabolite Profiling Reveals Acute Toxicity of Pentosidine on Adipose Tissue of Rats.

Background: Pentosidine is an advanced glycation end product that is commonly found in heat-processed foods. Pentosidine has been involved in the occurrence and development of some chronic diseases. It was reported that pentosidine exposure can impair the function of the liver and kidneys. Adipose tissue, as an active endocrine organ, plays an important role in maintaining the normal physiological function of cells. However, the metabolic mechanism that causes pentosidine to induce toxicity in adipose tissue remains unclear. Methods: In the study, thirty male Sprague-Dawley rats were divided into a normal diet group, low dose group, and high dose group. A non-targeted metabolomics approach was used to compare the metabolic profiles of adipose tissue between the pentosidine and normal diet groups. Furthermore, histopathological observation and body weight change analysis were performed to test the results of the metabolomics analysis. Results: A total of forty-two differential metabolites were identified. Pentosidine mainly disturbed twelve metabolic pathways, such as ascorbate and aldarate metabolism, glycine, serine, and threonine metabolism, sulfur metabolism, pyruvate metabolism, etc. Additionally, pyruvic acid was identified as a possible key upregulated metabolite involved in thirty-four metabolic pathways. α-Ketoglutaric acid was named as a probable key downregulated metabolite involved in nineteen metabolic pathways based on enrichment network analysis. In addition, histopathological analysis and body weight changes confirmed the results of the metabolomics analysis. Conclusions: These results provided a new perspective for the molecular mechanisms of adipose tissue toxicity induced by pentosidine.

Systemic amyloidosis following inflammatory bowel disease, follicular lymphoma, and diffuse large B-cell lymphoma: a case report

Systemic amyloidosis is a rare disorder characterized by the widespread deposition of misfolded amyloid proteins in several organs, leading to organ failure and potentially death if not promptly recognized. The occurrence of inflammatory bowel disease (IBD), follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) developing into systemic amyloidosis is uncommon. Here is a case of a 55-year-old Asian woman with a history of IBD, follicular lymphoma, and abdominal DLBCL who developed systemic amyloidosis affecting her gastrointestinal, cardiac, and renal organs. Gastrointestinal symptoms (abdominal pain and melena) initially manifested in this patient with systemic amyloidosis. She underwent treatment with three cycles of rituximab and bendamustine. However, she passed away after 2 months of hospitalization due to multiple organ failure. Hence, physicians must be vigilant in recognizing amyloidosis as a potential complication of lymphoma or other inflammatory diseases, as early recognition can contribute to improved clinical outcomes.

Method of intelligent agricultural pest image recognition based on machine vision algorithm

In recent years, people have paid increasing attention to smart agriculture. Its core technology is to combine information technology such as computer vision with agricultural production. In agricultural production, the occurrence of pests and diseases can seriously affect agricultural production. Therefore, in agricultural production, the diagnosis and identification of agricultural pests and diseases is the key to improve crop yield. Traditional machine vision methods often rely on feature extraction and classifier design, lack of strong learning and generalization ability, and can not effectively control crop diseases and pests in a timely manner. In order to solve this problem, this paper designs an agricultural pest recognition system based on machine vision algorithm of fuzzy recognition theory, and applies it to agricultural pest recognition. Compared with the traditional machine vision method, this method has obvious advantages, and can effectively improve the monitoring and early warning ability of crop diseases and pests. The experimental results show that the highest recognition rate of the machine vision optimization algorithm based on fuzzy recognition theory is 98.06%, and the lowest recognition error rate is 5.83%. It can be seen that the machine vision recognition algorithm based on fuzzy recognition theory has good recognition effect and can be used in agricultural pest recognition system to help farmers carry out agricultural production and reduce economic losses caused by diseases and pests.

Occurrence and seroprevalence of infectious viral, bacterial, and protozoal diseases among patients attending the Ore General Hospital in southwestern Nigeria

Infectious diseases caused by viruses, bacteria, protozoans, and fungi continue to pose significant challenges globally, with transmission routes including person-to-person contact, animal vectors, and environmental exposure. Despite global efforts to control these diseases, limited studies and resource constraints in Ore, Nigeria, have led to increasing prevalence, highlighting the need for targeted public health interventions. This study aimed to determine the distribution of infectious diseases among patients attending General Hospital Ore, Odigbo, Nigeria. Serum samples from consenting patients were assayed for the presence of malaria parasites, human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), Salmonella infection, Helicobacter pylori infection, high vaginal swab (HVS) results, and urinary tract infections (UTIs). The subjects included 1900 males (38.8%) and 3000 females (61.2%). The overall prevalence rates were as follows: HIV (40%), malaria (35%), typhoid (37.5%), HBsAg (20%), H. pylori (6.3%), HVS (45%), and UTIs (10%). The high rates of infectious diseases observed in this study, compared to rates reported elsewhere, suggest the need to strengthen public health measures and infection prevention strategies in the area. In addition, routine screening for these diseases and early passive or active immunization for vaccine-preventable diseases are essential to further reduce the burden of these infections.

Modeling Chronic Disease Mortality by Methods From Accelerated Life Testing.

We propose a parametric model for describing chronic disease mortality from cohort data and illustrate its use for Type 2 diabetes. The model uses ideas from accelerated life testing in reliability theory and conceptualizes the occurrence of a chronic disease as putting the observational unit to an enhanced stress level, which is supposed to shorten its lifetime. It further addresses the issue of semi-competing risk, that is, the asymmetry of death and diagnosis of disease, where the disease can be diagnosed before death, but not after. With respect to the cohort structure of the data, late entry into the cohort is taken into account and prevalent as well as incident cases inform the analysis. We finally give an extension of the model that allows age at disease diagnosis to be observed not exactly, but only partially within an interval. Model parameters can be straightforwardly estimated by Maximum Likelihood, using the assumption of a Gompertz distribution we show in a small simulation study that this works well. Data of the Cardiovascular Disease, Living and Ageing in Halle (CARLA) study, a population-based cohort in the city of Halle (Saale) in the eastern part of Germany, are used for illustration.

Sirt6 ameliorates high glucose-induced podocyte cytoskeleton remodeling via the PI3K/AKT signaling pathway

Background Podocyte injury plays an important role in the occurrence and progression of diabetic kidney disease (DKD), which leads to albuminuria. Cytoskeletal remodeling is an early manifestation of podocyte injury in DKD. However, the underlying mechanism of cytoskeletal remodeling has not been clarified. Histone deacetylase sirtuin6 (Sirt6) has been found to play a key role in DKD progression, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway directly regulates the cytoskeletal structure of podocytes. Whereas, the relationship between Sirt6, the PI3K/AKT pathway and DKD progression remains unclear. Methods Renal injury of db/db mice was observed by PAS staining and transmission electron microscope. Expression of Sirt6 in the glomeruli of db/db mice was detected by immunofluorescence. UBCS039, a Sirt6 activator, was used to explore the renal effects of Sirt6 activation on diabetic mouse kidneys. We also downregulating Sirt6 expression in podocytes using the Sirt6 inhibitor, OSS_128167, and induced upregulation of Sirt6 using a recombinant plasmid, after which the effects of Sirt6 on high glucose (HG)-induced podocyte damage were assessed in vitro. Podocyte cytoskeletal structures were observed by phalloidin staining. The podocyte apoptotic rate was assessed by flow cytometry, and PI3K/AKT signaling activation was measured by Western blotting. Results Db/db mice exhibited renal damage including elevated urine albumin-to-creatinine ratio (ACR), increased mesangial matrix, fused podocyte foot processes, and thickened glomerular basement membrane. The expression of Sirt6 and PI3K/AKT pathway components was decreased in db/db mice. UBCS039 increased the expressions of Sirt6 and PI3K/AKT pathway components and ameliorated renal damage in db/db mice. We also observed consistent Sirt6 expression was in HG-induced podocytes in vitro. Activation of the PI3K/AKT pathway via a Sirt6 recombinant plasmid ameliorated podocyte cytoskeletal remodeling and apoptosis in HG-treated immortalized human podocytes in vitro, whereas Sirt6 inhibition by OSS_128167 accelerated HG-induced podocyte damage in vitro. Conclusions Sirt6 protects podocytes against HG-induced cytoskeletal remodeling and apoptosis through activation of the PI3K/AKT signaling pathway. These findings provide evidence supporting the potential efficacy of Sirt6 activation as a promising therapeutic strategy for addressing podocyte injury in DKD.

SMYD1 modulates the proliferation of multipotent cardiac progenitor cells derived from human pluripotent stem cells during myocardial differentiation through GSK3β/β-catenin&ERK signaling.

The histone-lysine N-methyltransferase SMYD1, which is specific to striated muscle, plays a crucial role in regulating early heart development. Its deficiency has been linked to the occurrence of congenital heart disease. Nevertheless, the precise mechanism by which SMYD1 deficiency contributes to congenital heart disease remains unclear. We established a SMYD1 knockout pluripotent stem cell line and a doxycycline-inducible SMYD1 expression pluripotent stem cell line to investigate the functions of SMYD1 utilizing an in vitro-directed myocardial differentiation model. Cardiomyocytes lacking SMYD1 displayed drastically diminished differentiation efficiency, concomitant with heightened proliferation capacityof cardiac progenitor cells during the early cardiac differentiation stage. These cellular phenotypes were confirmed through experiments inducing the re-expression of SMYD1. Transcriptome sequencing and small molecule inhibitor intervention suggested that the GSK3β/β-catenin&ERK signaling pathway was involved in the proliferation of cardiac progenitor cells. Chromatin immunoprecipitation demonstrated that SMYD1 acted as a transcriptional activator of GSK3β through histone H3 lysine 4 trimethylation. Additionally, dual-luciferase analyses indicated that SMYD1 could interact with the promoter region of GSK3β, thereby augmenting its transcriptional activity. Moreover, administering insulin and Insulin-like growth factor 1 can enhance the efficacy of myocardial differentiation in SMYD1 knockout cells. Our research indicated that the participation of SMYD1 in the GSK3β/β-catenin&ERK signaling cascade modulated the proliferation of cardiac progenitor cells during myocardial differentiation. This process was partly reliant on the transcription of GSK3β. Our research provided a novel insight into the genetic modification effect of SMYD1 during early myocardial differentiation. The findings were essential to the molecular mechanism and potential interventions for congenital heart disease.

Prenylated Dihydroflavonol from Sophora flavescens Regulate the Polarization and Phagocytosis of Macrophages In Vitro

As an important member of innate immunity, macrophages show remarkable plasticity and heterogeneity, and play an important role in immune regulation, tissue development, homeostasis of the internal environment and injury repair. However, the excessive activation of macrophages is closely related to the occurrence and development of many diseases. The prenylated flavonoid structure is one of the characteristic structures isolated from Sophora flavescens, with anti-inflammatory, anti-tumor, anti-allergy and other effects. In this study, the effects of (2R)-3β,7,4′-trihydroxy-5-methoxy-8-prenylflavanone (TMP), a prenylated dihydroflavonol, on the polarization and phagocytosis of macrophages were systematically studied. In LPS-induced M1-type macrophages, TMP dose-dependently inhibited the expression of COX-2, iNOS and the secretion of NO, IL-1β, IL-6 and IL-18, showing an inhibitory effect on M1 polarization. Further experiments revealed that it was related to the inhibition of TLR4-related AKT/mTOR, MAPK and NF-κB signaling pathways; in IL-4-induced M2-type macrophages, TMP down-regulated the expression of M2-related Arg1, IL-10, TGF-β, CD206 and CD163, as well as the phosphorylation levels of AKT1 and STAT6. For macrophages in a physiological state, it was very important for cells to return from a stress state to a phenotypic stability in the M0 state. These results indicated that TMP negatively regulated the M1/M2 polarization of macrophages, and made them tend to M0 homeostasis, which might provide new theoretical and data support for explaining the anti-inflammatory immunoregulatory activity of Sophora flavescens.

Role of glucocorticoid receptor beta in the development of steroid resistance

Glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs for the treatment of inflammatory diseases, despite the fact that the resistance to them is increasing due to various circumstances. GC insensitivity is an important clinical issue that is associated with life-threatening disease progression. Currently, there is no reliable biomarker that can be used to define steroid resistance. According to several studies, increased expression of the glucocorticoid receptor beta (GR-β) isoform is associated with steroid resistance. The purpose of this review is to analyse the correlation between GR-β expression and the occurrence of steroid therapy-resistant diseases and to determine its potential as a biomarker. This review summarizes studies that point out increased GR-β expression in steroid-resistant groups of patients compared to steroid-sensitive groups. Articles included in the review focus on asthma, nasal polyposis, ulcerative colitis, and other chronic inflammatory diseases in which resistance to steroid therapy is observed. GR-β levels have also been shown to be elevated in patients with allergic rhinitis, Crohn's disease and rheumatoid arthritis. In most studies, higher levels of GR-β were detected in peripheral blood mononuclear cells (PBMC) by reverse transcription polymerase chain reaction (RT-PCR). Increased expression of GR-β is mostly associated with steroid resistance. Thus, it can potentially be used as a biomarker of steroid resistance-related disorders.

Microbes and pathogens associated with shrimps - implications and review of possible control strategies.

Shrimp aquaculture has been growing rapidly over the last three decades. However, high-density aquaculture together with environmental degradation has led to increased incidence of shrimp infections. Thus, devising and implementing effective strategies to predict, diagnose and control the spread of infections of shrimps are crucial, also to ensure biosecurity and sustainability of the food industry. With the recent advancements in biotechnology, more attention has been given to develop novel promising therapeutic tools with potential to prevent disease occurrence and better manage shrimp health. Furthermore, owing to the advent of the next-generation sequencing (NGS) platforms, it has become possible to analyze the genetic basis of susceptibility or resistance of different stocks of shrimps to infections and how sustainable aquaculture could be made free of shrimp diseases.

Seasonal detection of pathogens in honeybees kept in natural and laboratory conditions

The honeybee is one of the most important pollinators in the world. The frequently observed poor health of honeybee colonies can be caused by various factors, e.g. environmental pollution, nutritional stress, and climate changes. Moreover, honeybees are constantly exposed to a wide spectrum of pathogens, such as parasites, bacteria, and viruses. We examined the occurrence of various diseases in different-aged worker honeybees from two colonies kept in natural and laboratory conditions during spring, summer, and autumn in Poland. The honeybees were examined by PCR to detect infection with selected pathogens: Nosema ceranae, N. apis, N. bombi, Acarapis woodi, trypanosomatids, and neogregarines (Mattesia or Apicystis species) and by RT-PCR to identify deformed wing virus (DWV), black queen cell virus (BQCV), and acute bee paralysis virus (ABPV). DWV and N. ceranae turned out to be the dominant pathogens. Trypanosomatids and BQCV were also found in several samples. We did not detect the presence of the other pathogens: N. apis, N. bombi, A. woodi, neogregarines, or ABPV. As shown in the present study, the dynamics and occurrence of pathogens are influenced by keeping conditions, honeybee age, and seasonality.

Composition and Antioxidant Status of Human Milk of Women Living in Bydgoszcz (Poland).

The aim of this study was to compare cortisol concentrations, nutritional composition, and the antioxidant status of human milk of women living in Bydgoszcz (Poland), taking into account maternal factors (fertility, area of residence, economic activity, and breastfeeding period). The basic composition of human milk was evaluated using the MIRIS HMATM analyzer. The level of cortisol was determined by the enzyme-linked immunosorbent method. In order to determine the antioxidant activity, the DPPH radical method was used. It was observed that the concentration of cortisol in human milk in the group of women living in the city center was higher compared to the milk of women living on the outskirts of the city. In the group of women breastfeeding from 3 to 5 weeks after childbirth, the concentration of cortisol in milk was higher compared to the group of women breastfeeding less than 12 months of age and compared to the group of women lactating over 12 months of age. The antioxidant status of human milk was highest in the group of professionally active women and in the group of breastfeeding women from 3 to 5 weeks after childbirth. The basic composition and the caloric value of human milk differed statistically significantly in the study groups. Based on this study, it can be concluded that the composition and antioxidant status of human milk depends on maternal factors (fertility, professional activity, area of residence, and breastfeeding period). Higher cortisol concentrations in breast milk are probably determined by the area of residence (city center and associated higher noise/sound and stress levels) and lactation period (hormonal imbalance, fatigue, and postpartum period). Milk from economically active women shows greater protection against reactive oxygen species compared to milk from inactive women, protecting against the occurrence of diseases of civilization. Milk from breastfeeding women over 12 months of age also shows protection against reactive oxygen species, despite the fact that the highest level of antioxidant status of human milk occurs in the initial period of lactation.