Serum Levels Research Articles

Immunomodulatory potential of Lactobacillus helveticus KLDS 1.8701 postbiotics: By regulating the Th17/Treg balance

Maintaining homeostasis of the immune system is critical to human health. Postbiotics are inactive probiotics and their metabolites. Despite their numerous health benefits, the immunomodulatory potential of postbiotics has received less attention. The aim of this study was to explore the immunomodulatory influences of Lactobacillus helveticus postbiotics on cyclophosphamide (CTX)-induced immunocompromised mice and the underlying mechanism. The results showed a notable decrease in the immune function of the mice within the immunocompromised model. After treatment with Lactobacillus helveticus KLDS 1.8701 postbiotics, the immunity of mice was restored, as evidenced by an increase in organ index, proliferative capacity of splenic lymphocytes, NK cell activity, and serum immunoglobulin. It also promoted intestinal SIgA secretion and alleviated the degree of CTX-induced damage to the intestinal mucosal barrier. Meanwhile, Lactobacillus helveticus KLDS 1.8701 postbiotics demonstrated the ability to balance T helper cells 17 (Th17) and Regulatory T cells (Treg), exerting regulatory control over the serum levels of IL-17 and TGF-β, and thereby influencing the immune response. Therefore, Lactobacillus helveticus KLDS 1.8701 may be used as a potential functional food additive to prevent and treat CTX-induced immunocompromise.

Lung transplant list withdrawal in a liver transplant patient thanks to elexacaftor-tezacaftor-ivacaftor: a case report

BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) is a transmembrane conductance regulator modulator that significantly improves lung function in patients affected by cystic fibrosis (CF). This triple drug is currently not indicated in liver transplant patients, as clinical trials including subjects with previous solid organ transplantation are lacking.Case presentationWe report on a liver transplant girl with CF-related advanced pulmonary disease meeting clinical criteria for lung transplant, who started the triple modulator because she could not get on the lung transplant waiting list due to psycho-social motivations. Since initiation of ETI therapy, she has experienced a significant improvement in respiratory function and quality of life, without adverse effects.ConclusionsThis case shows that ETI therapy can represent a lifesaving drug for individuals without alternatives, even in liver transplant patients. The clinical benefits of the modulator overcome risks, which may be limited with a close drug monitoring of immunosuppressants serum levels and functional liver tests.

Iraqi patients with a single-nucleotide polymorphism of interleukin-10 -1082G/A and interleukin-6 -174G/C susceptibility to asthma

The effects of genetic variations in the IL-10 -1082G/A gene and IL-6 -174G/C gene, as well as the genotypes and alleles linked to the prevalence of asthma disease, were investigated using a molecular and immunological study. Between October 2018 and the end of July 2020, 40 healthy individuals (20 females and 20 males) served as a control group for the study, which involved 50 asthmatic patients (31 females and 19 males) at the Allergy Centre, Al-Anbar Teaching Hospital, in Al-Anbar City. The study used the Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) technique to show that the single nucleotide polymorphisms IL-10 -1082G/A and IL-6 -174G/C had a considerably high prevalence rate (P<0.05) among asthma case and that there was an association between the polymorphism and the asthma risk. The findings indicate that asthma patients had considerably higher (P<0.05) IL-10 A alleles and heterozygous GA genotypes (1082G/A) compared to the control group. Genetic variations affecting IL-10 production and the genotypes affecting IL-10 serum levels are associated with the occurrence of asthma and are attributed to the IL-10 -1082G/A promoter gene polymorphism. There was a strong correlation between cytokine levels, of disease development, and the genotypes of the AA and AG genes, indicating that IL-10 -1082A/G predisposition to asthma may be influenced by the gene promoter polymorphism. Asthma development and immunological markers (IL-10) are substantially correlated. One theory links allergic rhinitis to both the development of asthma and its risk. Inducing long-term immunological and clinical tolerance in patients was a good use of HDM immunotherapy. The current study's findings indicate a substantial difference between the asthma patients and the control group in terms of gene type and allele frequency of the IL-6 -174G/C polymorphism. The patients exhibited a higher prevalence of the G allele and the GG homozygous genotype than the control group. Therefore, it was shown that those with GG genotypes had a 2-fold increased probability of having asthma, indicating that patients were more prone to the condition.

Effect of dairy products fortified with vitamin d3 on restless legs syndrome in women with premenstrual syndrome, abdominal obesity and vitamin d deficiency: a pilot study

BackgroundsRestless legs syndrome (RLS) is an unpleasant condition that affects the quality of life of patients. Its prevalence in increased in women with premenstrual syndrome (PMS). Vitamin D plays a key role in female reproduction through its impact on calcium homeostasis and neurotransmitters. We aimed to evaluate the effect of dairy products fortified with Vitamin D3 on RLS in women with PMS.Materials and methodsWe conducted a 2.5-month, randomized, total-blinded clinical trial to evaluate the effectiveness of low-fat milk and yogurt fortified with vitamin D on RLS in women with PMS. Among 141 middle-aged women with abdominal obesity, 71 and 70 cases received fortified and non-fortified low-fat dairy products, respectively. All subjects completed a Symptoms Screening Tool (PSST) and RLS questionnaires.ResultsThe results showed that in the women with severe PMS (PSST > 28), serum levels of vitamin D increased significantly following vitamin D fortification. The mean restless legs score in the severe PMS subgroup (PSST > 28) was significantly lower after the intervention (p < 0.05. Serum Vitamin D levels significantly differed between intervention and control groups in all individuals (PSST < 19, PSST 19–28, and PSST > 28) (p < 0.05), but no significant differences were found between RLS scores of the intervention and control groups in the three PMS subgroups (p > 0.05).ConclusionFortifying dairy products with vitamin D3 can increase the serum levels of vitamin D and reduce the RLS severity in women with severe PMS, but not in other groups.

Evaluation of estriol levels in women with preeclampsia in Nnewi, South-East Nigeria

Preeclampsia is a life-threatening pregnancy-induced disorder characterized by the presence of hypertension and proteinuria occurring after 20 weeks of gestation in a previously normotensive and aproteinuric woman. This study is aimed at investigating the maternal serum levels of estriol in pregnant women with preeclampsia. This is an analytical cross-sectional study including a total of 90 pregnant women aged 18-41years at 26-40 weeks of gestation, according to the last date of menstruation and ultrasonographic measurements. Forty five of these were preeclamptic while the other forty five were apparently healthy individuals. Preeclampsia was determined by proteinuria ≥30mg/dl or ≥1+ using a urine dipstick and sphygmomanometer blood pressure reading of ≥ 140/90 mmHg using ausculatory method. BMI was calculated from weight and height measurements of each participant. Estriol (E3) levels were determined utilizing the double-antibody sandwich enzyme linked immunosorbent assay technique. Hypothesis testing was done using the student’s t-test for continuous variables, Chi-square test for categorical variables and Pearson’s correlation for the tests of association. Statistical significance was set at p&lt;0.05. The mean serum values of E3 were significantly lower in women with preeclampsia (124.18±22.40) compared with the apparently healthy control counterparts (141.41±20.68, p&lt;0.001). A moderate negative correlation was observed between maternal serum estriol level and BMI in the preeclamptic group (r = -0.589; p&lt;0.001). There existed a strong negative correlation between maternal serum estriol level and systolic (r = -0.738; p&lt;0.001) as well as diastolic (r = -0.711; p&lt;0.001) blood pressures in women with preeclampsia. Preeclampsia is associated with lower maternal serum levels of estriol which may play a significant role in the pathogenesis of the disorder.

The association between fat distribution and α1-acid glycoprotein levels among adult females in the United States

BackgroundVisceral fat accumulation and obesity-induced chronic inflammation have been proposed as early markers for multiple disease states, especially in women. Nevertheless, the potential impact of fat distribution on α1-acid glycoprotein(AGP), a marker of inflammation, remains unclear. This research was conducted to investigate the relationships among obesity, fat distribution, and AGP levels.MethodsA cross-sectional observational study was performed using blood samples from adult females recruited through the National Health and Nutrition Examination Survey from 2015 to 2018. Serum levels of AGP were measured using the Tina-quant α-1-Acid Glycoprotein Gen.2 assay. Based on the fat distribution data obtained from dual-energy X-ray absorptiometry assessments, body mass index (BMI), total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android fat/gynoid fat ratio (AGR), visceral percent fat (VPF), subcutaneous percent fat (SPF), visceral fat/subcutaneous fat ratio (VSR) were used as dependent variables. To investigate the link between fat distribution and AGP, multivariate linear regression analysis was utilized. Furthermore, a sensitivity analysis was also performed.ResultsThe present study included 2,295 participants. After adjusting for covariates, BMI, TPF, APF, GPF, VPF, and SPF were found to be positively correlated with AGP levels (BMI: β = 23.65 95%CI:20.90–26.40; TPF: β = 25.91 95%CI:23.02–28.80; APF: β = 25.21 95%CI:22.49–27.93; GPF: β = 19.65 95%CI:16.96–22.34; VPF: β = 12.49 95%CI:9.08–15.90; SPF: β = 5.69, 95%CI:2.89–8.49; AGR: β = 21.14 95%CI:18.16–24.12; VSR: β = 9.35 95%CI:6.11–12.59, all P < 0.0001). All the above indicators exhibited a positive dose–response relationship with AGP. In terms of fat distribution, both AGR and VSR showed positive associations with AGP (P for trend < 0.0001). In particular, when compared to individuals in tertile 1 of AGR, participants in tertiles 2 and 3 had 13.42 mg/dL (95% CI 10.66–16.18) and 21.14 mg/dL (95% CI 18.16–24.12) higher AGP levels, respectively. Participants in the highest tertile of VSR were more likely to exhibit a 9.35 mg/dL increase in AGP compared to those in the lowest tertile (95% CI 6.11–12.59).ConclusionsOverall, this study revealed a positive dose-dependent relationship between fat proportion/distribution and AGP levels in women. These findings suggest that physicians can associate abnormal serum AGP and obesity with allow timely interventions.

Vitamin D levels in Coronavirus-infected Individuals and its Correlation with Certain Hematological Markers

The world and nearly all our health care system were confronted by a significant threat which was declared by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Determining the SARS-CoV-2 or COVID-19’s prognostic and modifiable measures surely would largely contribute to outcome improving despite the deficiency of causative therapy that affected nearly 200 million people, 3.5 million fatal incidences, and it is still airborne. The research in hand examined probable relations between the levels of vitamin D (VitD) and immunological markers. Hence, a sample of 200 lecturers and students from Cihan University-Erbil were assigned, (150 males, 50 females) whom ages were between 22 to 25, with some respondents were treated from a previous COVID-19 infection. The results showed that 98 (or 49%) of the 200 samples had Covid-19 infection. Males 60/98 had a greater prevalence rate (61%), whilst females 38/98 had a lower rate (39%). According to immunological ELISA results, every patient had positive IgG antibodies and negative IgM antibodies. Compared to the healthy group, the serum levels of IgE rose considerably in Covid-19 patients. However, when compared to the healthy group, the serum level of vitamin D3 in the Covid-19 recovered patients showed a considerable reduction. The mean results for hematological parameters indicated a non-significant increase in the number of red blood cells relative to the healthy group, but a significant increase in the WBC count, Hb concentration, and platelets. Thus, the result indicates the necessity for interventional studies on vitamin D supplementation in SARS-CoV-2 infected persons by showing a correlation between vitamin D deficit and WBC count during COVID-19 recovery.

Genetic variants in the TNF pathway impact TNFi response in a mixed population with rheumatoid arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune inflammatory disease that mainly affects the joints, on reducing functional capacity and impacting quality of life. Cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) are crucial in the pathogenesis and treatment of this disease. Some patients using TNF inhibitors (TNFi) do not respond or lose their response to these medications. Clinical, sociodemographic, and genetic data were used to evaluate the associations of single nucleotide polymorphisms (SNP) in TNF, TNFRSF1A, and TNFRSF1B genes with the diagnosis of RA, standardized score results, laboratory tests, and response to TNFi. In one subsample, TNF and IL-6 serum levels cytokines were performed. A total of 654 subjects (360 healthy controls and 294 diagnosed with RA) were included in the analysis. Higher levels of TNF have been found in individuals diagnosed with RA. IL-6 levels were higher in individuals who did not respond to TNFi treatment, while responders had levels comparable to those without the disease. No associations were found between the SNPs studied and the diagnosis of RA; however, rs767455-C seems to play a role in the response to golimumab treatment, being related to better therapeutic response and lower mean serum leukocyte levels. In addition, rs1061622-G was associated with poorer functional capacity and rs1800629-A was associated with higher leukocyte values and serum transaminase levels. The rs1061622-G and rs767455-C may play a role in the response to TNFi treatment, especially for patients using golimumab, although they do not seem to be associated with the diagnosis of RA. Polymosphisms in the TNF pathway may impact baseline levels of immune cells and markers of renal and hepatic function in RA patients. Our results highlight the importance of evaluating the impact of these polymorphisms on TNFi response and safety, particularly in larger-scale studies.

Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study.

In this prospective observational study, we aimed to investigate the serum levels of sirtuin (SIRT)3 in epilepsy patients and its association with the severity of the disease. This prospective observational study included 203 patients with symptomatic epilepsy and 100 healthy controls who visited our hospital from November 2019 to November 2022. The severity of the disease in epilepsy patients was assessed using the National Hospital Seizure Severity Scale (NHS3). We used enzyme-linked immunosorbent assay to measure the serum levels of SIRT3, interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha, and C-reactive protein in all patients. In addition, the cognitive function of all study participants was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment (MOCA). All data were analyzed using SPSS 25.0 software. The MOCA scores of the epilepsy patients were significantly lower compared to the healthy volunteers (P < 0.05). The serum SIRT3 levels were decreased significantly in patients with refractory epilepsy (183.16 ± 17.22 pg/mL) compared to non-refractory epilepsy patients (199.00 ± 18.68 pg/mL). In addition, serum SIRT3 levels were negatively correlated with the inflammatory factors IL-6 (Pearson's correlation -0.221, P = 0.002) and NHS score (Pearson's correlation -0.272, P < 0.001) of epilepsy patients, while positively correlated with MOCA scores (Pearson's correlation 0.166, P = 0.018). Furthermore, the receiver operating characteristic curve demonstrated that serum SIRT3 could be used to diagnose epilepsy, as well as refractory epilepsy. Finally, logistic regression analysis showed that SIRT3 (OR = 1.028, 95%CI: 1.003-1.054, P = 0.028), IL-6 (OR = 0.666, 95%CI: 0.554-0.800, P < 0.001), IL-1β (OR = 0.750, 95%CI: 0.630-0.894, P = 0.001), and NHS3 (OR = 0.555, 95%CI: 0.435-0.706, P < 0.001) were risk factors for refractory epilepsy. In conclusion, our findings demonstrated that serum SIRT3 levels were significantly decreased in epilepsy patients and further decreased in patients with refractory epilepsy. This study might provide new therapeutic targets and comprehensive treatment strategies for epilepsy patients.

Genetic insights into serum cathepsins as diagnostic and therapeutic targets in knee and hip osteoarthritis

Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice.

Increased level of GATA3-AS1 long non-coding RNA is correlated with the upregulation of GATA3 and IL-4 genes in multiple sclerosis patients.

Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies.

Description of Pre-Hemodialysis Serum Phosphate in Late-Stage Kidney Disease Patients of Productive Age (15-64 Years) at the Indonesian Christian University General Hospital

In Indonesia, end-stage kidney disease is still a health problem that needs attention. End-stage kidney disease or abbreviated as PGTA reflects the fifth stage of chronic kidney disease, at this stage, there is a buildup of toxins, fluids, electrolytes, and the remains of the body's metabolism. In stage 5 chronic kidney disease, the glomerular filtration rate decreases &lt; 15 ml/minute / 1.73 m2 and has occurred for 3 months or more. One of the clinical complications of end-stage renal disease is an increase in phosphate levels in the patient's blood serum (hyperphosphatemia), this occurs due to disruption of the kidney's phosphate excretion function. Hyperphosphatemia in PGTA patients can result in hyperparathyroidism, soft tissue, and cardiovascular calcification, and affect bone mineral disorders. In kidney disease patients with a glomerular filtration rate &lt; 30 ml/minute / 1.73m2, the prevalence of hyperphosphatemia complications increased to 23%. This study aims to determine the description of pre-hemodialysis inorganic phosphate levels in the serum of PGTA patients of productive age (15-64 years) undergoing hemodialysis at the Indonesian Christian University General Hospital for the period January 2022. The research conducted was a descriptive study, to determine the description of phosphate levels serum of PGTA patients. The data used in this study is primary data by directly taking the blood of 20 pre-hemodialysis patients with end-stage kidney disease and then examining it in the laboratory. In this study, the results showed that 10 PGTA patients (50%) experienced an increase in serum inorganic phosphate levels above normal (&gt;5 mg/dl). Meanwhile, 9 people (45%) had normal serum phosphate levels (2.5 - 5 mg/dl), and 1 other person had below normal serum phosphate levels (&lt;2.5 mg/dl). Keywords: Inorganic Phosphate, Hemodialysis, Hyperphosphatemia, End Stage Renal Disease

Microencapsulated rice bran alleviates hyperlipidemia induced by high-fat diet via regulating lipid metabolism and gut microbiota.

Hyperlipidemia has been suggested to be associated with dysregulation of lipid metabolism and gut microbiota. The present study prepared microencapsulated rice bran (MRB) with high stability based on in situ rice bran oil embedding and investigated the effects of MRB on lipid metabolism and gut microbiota in hyperlipidemic mice induced by high-fat diet (HFD). Results showed that compared to HFD fed mice, lipid levels in serum and hepatic lipid accumulation were reduced in mice fed with MRB, which was potentially associated with the fact that MRB decreased the expression of genes related to lipogenesis (Srebp1c, Acc, Hmgcr, and Fas) and increased the expression of genes related to lipid catabolism (Hsl, Atgl) and oxidation (Acox, Cpt1, Ucp1) (p<0.05). In gut, MRB supplementation significantly elevated the abundance of beneficial bacteria, such as Dubosiella and Faecalibaculum. In addition, significant increase in short-chain fatty acid was observed in mice from MRB groups when compared to HFD groups (p<0.05). Overall, this study suggested that MRB could alleviate the hyperlipidemia induced by HFD, which was related to the alteration of lipid metabolism and gut microbiota.

Ultrasensitive carbon nanotube-bridged MXene conductive network arrays for one-step homogeneous electrochemical immunosensing of tumor markers

Developing non-passivating and fully integrated electrode arrays for point-of-care testing of carcinoembryonic antigen (CEA) is crucial, as the serum level of CEA is closely associated with colorectal cancer. Herein, we propose a simple, low-cost, and eco-friendly template-assisted filtration method for the scalable preparation of carbon nanotube-bridged Ti3C2Tx MXene (MX@CNT) electrode arrays with a conductive network. Furthermore, we fabricate a homogeneous electrochemical (HEC) sensor for CEA detection by integrating a magnetic-bead-based alkaline phosphatase-linked immunoassay (MB-aElisa), which enables the in-situ generation of the electroactive substance 1-naphthol (1-NP). Benefiting from the unique electrochemical characteristics of a MX@CNT electrode array, such as ultra-low background signal and superior electrocatalytic activity towards the hydrolyzed 1-NP, the MB-aElisa-based HEC sensor specifically measures CEA within a detection range spanning from 0.005 to 1.0 ng mL−1, achieving a detection limit of 1.6 pg mL−1. Subsequently, this biosensing prototype is successfully utilized for the detection of CEA in serum specimens obtained from colorectal cancer patients. More importantly, the integration of MB-aElisa with a MX@CNT electrode array not only marks a significant advancement but also enables the creation of a one-step homogeneous electrochemical immunosensing platform, serving as a paradigm for the highly sensitive and selective measurement of trace tumor markers in complex biological samples.

FGF-21 Level is higher in patients with breast cancer, a candidate for a new biomarker?

Aims: Fibroblast Growth Factor 21 (FGF-21) is a member of the FGF family involved in biological processes such as embryonic development. cell growth. morphogenesis. tissue repair. tumour growth and invasion. with mitogenic and cytogenetic activity at 19q13.33.Breast cancer is a deadly and increasing disease in women. and recent studies have shown a relationship between some cancers. including breast cancer. and hormones secreted from adipose tissue.The aim of the present study was the measurement of FGF-21 levels in patients with breast cancer and its association with breast cancer. Methods: The study included 39 patients with newly diagnosed breast cancer and 39 healthy controls. During the patients’ routine blood tests. a venous blood sample was taken and the serum levels of FGF-21 were determined by ELISA. Results: Demographic and laboratory data were compared between the newly diagnosed breast cancer group and the control group. The control group consisted of 39 participants with a mean age of 52.49 ± 7.02 years. In the patient group. 39 participants with a mean age of 52.15 ± 6.21 years were included in the study. there was no statistical difference regarding age(p&gt;0.05).In the control group. the mean FGF-21 level was 121.35 ± 88.4 pg/ml. while the mean FGF-21 level in the patient group was 171 ± 117.45 pg/ml. a statistically significant difference was detected(p value=0.036). Conclusion: FGF-21 is thought to have significant and beneficial effects on glucose. lipid and energy metabolism. as well as slowing the growth of cancer cells. and may later be used as a biological marker for breast cancer.

House dust mite-induced asthma exacerbates Alzheimer's disease changes in the brain of the AppNL-G-F mouse model of disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal death. Besides aging, various comorbidities increase the risk of AD, including obesity, diabetes, and allergic asthma. Epidemiological studies have reported a 2.17-fold higher risk of dementia in asthmatic patients. However, the molecular mechanism(s) underlying this asthma-associated AD exacerbation is unknown. This study was designed to explore house dust mite (HDM)-induced asthma effects on AD-related brain changes using the AppNL-G-F transgenic mouse model of disease. Male and female 8-9 months old C57BL/6J wild type and AppNL-G-F mice were exposed to no treatment, saline sham, or HDM extract every alternate day for 16 weeks for comparison across genotypes and treatment. Mice were euthanized at the end of the experiment, and broncho-alveolar lavage fluid (BALF), blood, lungs, and brains were collected. BALF was used to quantify immune cell phenotype, cytokine levels, total protein content, lactate dehydrogenase (LDH) activity, and total IgE. Lungs were sectioned and stained with hematoxylin and eosin, Alcian blue, and Masson's trichrome. Serum levels of cytokines and soluble Aβ1-40/42 were quantified. Brains were sectioned and immunostained for Aβ, GFAP, CD68, and collagen IV. Finally, frozen hippocampi and temporal cortices were used to perform Aβ ELISAs and cytokine arrays, respectively. HDM exposure led to increased levels of inflammatory cells, cytokines, total protein content, LDH activity, and total IgE in the BALF, as well as increased pulmonary mucus and collagen staining in both sexes and genotypes. Levels of serum cytokines increased in all HDM-exposed groups. Serum from the AppNL-G-F HDM-induced asthma group also had significantly increased soluble Aβ1-42 levels in both sexes. In agreement with this peripheral change, hippocampi from asthma-induced male and female AppNL-G-F mice demonstrated elevated Aβ plaque load and increased soluble Aβ 1-40/42 and insoluble Aβ 1-40 levels. HDM exposure also increased astrogliosis and microgliosis in both sexes of AppNL-G-F mice, as indicated by GFAP and CD68 immunoreactivity, respectively. Additionally, HDM exposure elevated cortical levels of several cytokines in both sexes and genotypes. Finally, HDM-exposed groups also showed a disturbed blood-brain-barrier (BBB) integrity in the hippocampus of AppNL-G-F mice, as indicated by decreased collagen IV immunoreactivity. HDM exposure was responsible for an asthma-like condition in the lungs that exacerbated Aβ pathology, astrogliosis, microgliosis, and cytokine changes in the brains of male and female AppNL-G-F mice that correlated with reduced BBB integrity. Defining mechanisms of asthma effects on the brain may identify novel therapeutic targets for asthma and AD.

Role of Interleukin 6 in Acute Pancreatitis: A Possible Marker for Disease Prognosis

Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.

Association between serum cytokeratin 18 and N-terminal procollagen III propeptide in patients with biopsy-proven nonalcoholic fatty liver disease*

ABSTRACT Liver biopsy is still the gold standard in the staging of nonalcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide. However, being an invasive method, liver biopsy has limited use in clinical practice. The aim of this study was to determine the relationship between serum levels of cytokeratin 18 (CK-M30) and N-terminal procollagen III propeptide (PIIINP) in patients with biopsy-proven NAFLD. The study was carried out on volunteers, including both healthy individuals and patients pre-diagnosed with NAFLD. The liver biopsies were re-assessed by applying the Steatosis, Activity, Fibrosis/Fatty Liver Inhibition of Progression (SAF/FLIP) algorithm. At the end of the study, frozen serum samples (−80 °C) were analyzed using commercial kits. CK18-M30 and PIIINP levels significantly differed in all study groups. There was no significant correlation between serum levels of CK18-M30 and PIIINP in healthy individuals but there was a significant positive correlation between CK18-M30 and PIIINP levels in NAFLD (NAFL-nonalcoholic steatohepatitis (NASH)) groups. CK18-M30 was better than PIIINP at distinguishing between NAFL and NASH. The results obtained for biopsy-proven NAFLD demonstrated that both PIIINP and CK18-M30 were partly associated with histological parameters and could aid in distinguishing between NASH and NAFL.

Diosgenin Reduces Acute Kidney Injury and Ameliorates the Progression to Chronic Kidney Disease by Modifying the NOX4/p65 Signaling Pathways.

Acute kidney injury (AKI), if not well controlled, may progress to chronic kidney disease (CKD). Diosgenin is a natural phytosteroid sapogenin from plants. This study aimed to investigate the mechanistic effects of diosgenin on AKI and AKI related development of CKD. The mouse model of ischemia/reperfusion (I/R)-induced AKI was used, and its progressive changes were followed. Human renal proximal tubular epithelial cells were used, and hypoxia stimulation was applied to mimic the in vivo I/R. Diosgenin, given after renal injury, preserved kidney function, as evidenced by a reduction in serum levels of BUN, creatinine, and UACR in both acute and chronic phases of AKI. Diosgenin alleviated I/R-induced tubular injury and prevented macrophage infiltration and renal fibrosis in AKI mice. Furthermore, diosgenin also mitigated the development of CKD from AKI with reduced renal expression of inflammatory, fibrotic, and epithelial-mesenchymal transition markers. In human renal tubular epithelial cells, diosgenin downregulated the hypoxia-induced oxidative stress and cellular damages that were dependent on the NOX4/p65 signaling pathways. Taken together, diosgenin treatment reduced I/R-induced AKI and ameliorated the progression to CKD from AKI probably by modifying the NOX4/p65 signaling pathways.

The toxic effects of Helicobacter pylori and benzo(a)pyrene in inducing atrophic gastritis and gut microbiota dysbiosis in Mongolian gerbils

AbstractFood chemical and microbiological contamination are major global food safety issues. This study investigated the combined effects of the food‐borne pathogen Helicobacter pylori (H. pylori) and the pollutant benzo(a)pyrene (Bap) on atrophic gastritis and gut microbiota in Mongolian gerbils. The results demonstrated that simultaneous administration of H. pylori and Bap caused more severe weight loss, DNA damage, and gastritis in Mongolian gerbils compared with those exposed to H. pylori or Bap alone. The combination also significantly increased the serum level of proinflammatory cytokines, including IL‐1β (p &lt; .05), IL‐6 (p &lt; .0001), and TNF‐α (p &lt; .05). Additionally, the H. pylori and Bap combination altered the composition of gut microbiota in Mongolian gerbils: the relative abundance of Lactobacillus and Ligilactobacillus at the genus level (p &lt; .05) was significantly reduced while the relative abundance of Allobaculum and Erysipelotrichaceae enhanced (p &lt; .0001, p &lt; .05). Our study revealed that the synergy of H. pylori and Bap can boost the development of atrophic gastritis and lead to gut microbiota dysbiosis in Mongolian gerbils, which provides essential implications for preventing contaminated foods to sustain life and promote well‐being.