Altered Profile Research Articles

High Sensitive C-Reactive Protein and Lipid Profile Alteration In Subclinical Hypothyroidism for Cardiovascular Risk Assessment.

The purpose of this study was to investigate the association of subclinical hypothyroidism with High sensitive C-reactive protein and lipid profile which can predispose to development of Cardiovascular disease. This hospital-based comparative cross-sectional study was conducted for a period of six months. A total of 71 patients with subclinical hypothyroidism and 37 healthy control subjects were enrolled for the study. Thyroid hormones, lipid profile, hs- CRP were measured and lipid variables were used to calculate lipid indices. Student t-test were used to compare means and Spearmans correlation was done to determine the association between variables. ROC curve analysis was used to determine the diagnostic value of tests. Out of 71 cases and 37 control, majority had female preponderance (71.8% in case and 83.8% in control). The mean values between case and control groups for High sensitive C-Reactive Protein, Atherogenic index of plasma, Lipoprotein combined index and non-High Density Lipoprotein cholesterol were statistically significant. There was positive correlation between Thyroid Stimulating Hormone and High sensitive C-Reactive Protein r=0.492, p 0.001, Atherogenic index of plasma and Thyroid Stimulating Hormone r=0.430, p 0.001, Lipoprotein combined index and Thyroid Stimulating Hormone (r=0.269, p =0.005), Thyroid Stimulating Hormone and non-High Density Lipoprotein cholesterol (r=0.308, p=0.001) and Atherogenic Index and Low Density Lipoprotein r= 0.712, p 0.001 with weak correlation with statistical significance as per Spearmans correlation. Area under ROC curve for High sensitive C-Reactive Protein indicated it as a positive biomarker for cardiovascular risk assessment. Our findings shows that sch patients are more at risk of cvd and hs-crp contributes as a significant marker, thus requiring timely intervention. Lipid indices and AIP must be determined even in patients with a normal lipid profile to improve atherogenic risk.

Exploring the protective role of green tea extract against cardiovascular alterations induced by chronic REM sleep deprivation via modulation of inflammation and oxidative stress

BackgroundChronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects.MethodsA total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model.ResultsChronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels.ConclusionThese findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.

Lesional Psoriasis is Associated With Alterations in the Stratum Corneum Ceramide Profile and Concomitant Decreases in Barrier Function.

Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non-lesional skin of 26 patients and 10 healthy controls were analysed using in-depth ceramide lipidomics by liquid chromatography-mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non-lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non-lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction.

Altered B-cell, plasma cell, and antibody immune profiles in blood of patients with systemic mastocytosis

Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated constitutively activated mast cells (MCs) that release MC mediators, which might act on the tumor microenvironment including other immune cells. To investigate the blood distribution of B-cell, plasma cell (PC), and antibody isotype compartments in patients with SM. We used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B cells, PCs, and their subsets in blood of 108 patients with SM (35 bone marrow mastocytosis [BMM] cases, 64 indolent SM [ISM] cases, 9 aggressive SM [ASM] cases) versus 117 age-matched healthy donors and paired bone marrow samples of 31 patients with SM versus 17 controls, respectively. In parallel, IgM, IgD, IgG, IgA, and IgE plasma levels were measured. Compared with healthy donors, patients with SM showed increased immature B-cell production in bone marrow (P= .003) associated with greater release of pre-germinal center immature (P< .001) and naive CD5+ B lymphocytes (P< .001) to blood, but a pronounced decrease in PC counts of all different IgH isotypes and subclasses (P≤ .001) together with overall increased IgM (P= .001) and IgD (P< .001) plasma levels. Different immune profiles were found per diagnostic subtype of disease with progressively greater counts in blood of immature B lymphocytes together with decreased IgMD+, IgG2+, IgA1+, and IgA2+ memory B cells (P≤ .032) and elevated IgM (P= .017) plasma levels in cases of ASM, increased IgM (P= .001) and IgD (P= .001) plasma levels in ISM cases, and exacerbated IgE (P< .001) with decreased IgG (P= .008) plasma levels in BMM cases. Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of patients with SM, consistent with distinctly altered antibody isotype profiles in plasma of patients with BMM versus ISM versus ASM.

A dTDP-L-rhamnose 4-epimerase required for glycopeptidolipid biosynthesis in Mycobacterium abscessus

Mycobacterium abscessus causes severe lung infections in cystic fibrosis patients and exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in the S-to-R transition but the underlying molecular mechanisms of this transition remain incompletely understood. Herein, we characterized MAB_4111c in relation to GPL synthesis and investigated the effects of MAB_4111c deletion in M. abscessus pathogenicity. An enzymatic assay indicated that MAB_4111c, also designated Tle for Talose epimerase, is converting dTDP-L-Rhamnose into dTDP-6-deoxy-L-Talose. A tle deletion mutant was constructed in the S variant of M. abscessus and relative areas of Rhamnose and 6-deoxy-Talose and their methylated forms expressed as ratios of total monosaccharides, showed an altered GPL profile lacking 6-deoxy-Talose. Thus, Tle provides dTDP-6-deoxy-L-Talose, subsequently used by the glycosyltransferase Gtf1 to transfer 6-deoxy-Talose to the GPL backbone. Strikingly, the tle mutant exhibited a R morphotype, showed impaired sliding motility and biofilm formation, and these phenotypes were rescued upon functional complementation. Moreover, deletion of tle in M. abscessus results in increased pathogenicity and killing in zebrafish embryos. Together, our results underscore the importance of the dTDP-L-Rhamnose 4-epimerase activity in GPL biosynthesis and in influencing M. abscessus virulence.

Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.

Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure. Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted invitro using patient-derived cells and invivo by employing murine and human xenograft pre-clinical disease models. We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive invivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease. Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis. This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.

Statement complementing the EFSA Scientific Opinion on application (EFSA-GMO-NL-2015-126) for authorisation of food and feed containing, consisting of and produced from genetically modified soybean MON 87705 × MON 87708 × MON 89788.

Following a request from the European Commission, the GMO Panel assessed additional information related to the application for authorisation of food and feed containing, consisting of and produced from genetically modified soybean MON × MON 87708 × MON 89788 (EFSA-GMO-NL-2015-126). The applicant conducted a 90-day feeding study on GM soybean MON 87705 and provided a proposal for post-market monitoring considering the altered fatty acid profile of GM soybean MON 87705 × MON 87708 × MON 89788, to fulfil the deficiencies identified by EFSA GMO Panel, addressing elements that remained inconclusive from a previous EFSA scientific opinion issued in 2020. The GMO Panel concludes that the 90-day feeding study on GM soybean MON 87705 is in line with the requirements of Regulation (EU) No 503/2013 and that no treatment-related adverse effects were observed in rats after feeding diets containing soybean MON 87705 meals at 30% or 15% for 90 days. The GMO Panel reiterates the recommendation for a PMM for food in accordance with Regulation (EC) No 1829/2003 and Regulation (EU) No 503/2013 and concludes that the proposal provided by the applicant is in line with the recommendations described for the PMM plan of soybean MON 87705 × MON 87708 × MON 89788 in the adopted scientific opinion. Taking into account the previous assessment and the new information, the GMO Panel concludes that soybean MON 87705 × MON 87708 × MON 89788, as assessed in the scientific opinion on application EFSA-GMO-NL-2015-126 and in the supplementary toxicity study, is as safe as its non-GM comparator and the non-GM reference varieties tested and does not represent a nutritional concern in humans and animals, within the scope of this application.

TMPRSS2:ERG Gene Fusion Might Predict Resistance to PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer.

The emergence of novel DNA damage repair (DDR) pathways in molecular-target therapy drugs (MTTD) has shown promising outcomes in treating patients with metastatic castration-resistant prostate cancer (mCRPC). About 25% of mCRPC patients have actionable deleterious aberrations in DDR genes, primarily in the homologous recombination (HR) pathway. However, the response rate in patients with BRCA1/2 or mutations in HRR-related genes is only 45%-55%, when exposed to poly ADP ribose polymerase (PARP) inhibitor-based therapy (PARPi). A frequent characteristic feature of prostate cancer (PC) is the occurrence of genomic rearrangement that affects the transmembrane protease serine 2 (TMPRSS2) and E26 transformation-specific (ETS)- transcription factor-related gene (ERG). In this study, a total of 114 patients with mCRPC had their RNA and DNA sequenced using next-generation sequencing. Based on their genetic profile of deleterious gene alterations of BRCA1/2 or ATM, six patients were selected for PARPi. Patients with TMPRSS2:ERG gene fusion and homozygous alteration in ATM or BRCA2 (n=2) or heterozygous alterations (BRCA1 or BRCA2) and lack of TMPRSS2:ERG gene fusion (n=2) did not show clinical benefit from PARPi (treatment duration <16 weeks). In contrast, patients (n=2) without TMPRSS2:ERG gene fusion and homozygous deleterious alterations in ATM or BRCA2 all had clinical benefit from PARPi (treatment duration ≥16 weeks). The TMPRSS2:ERG transcript product might be used as a PARPi resistance biomarker.

Effect of sediment erosion on pressure pulsations in a large Pelton turbine

AbstractPelton turbines functioning in sandy river environments often encounter difficulties due to the swift movement of sediment particles, leading to erosion and damage to overflow components. These challenges can result in operational instability, particularly noticeable in large turbines. Pressure pulsation is crucial for turbine stability, and alterations in overflow component profiles caused by sediment erosion can worsen pressure pulsations. This study utilizes numerical simulations to analyze turbine pressure pulsations based on surface profile changes of runner buckets after 2 and 4 years of sediment erosion in a single 500 MW large‐scale Pelton turbine. Our findings reveal that erosion leads to a gradual decrease in pressure pulsation along the bucket's splitting edge from the notch to the root. After 4 years of erosion and wear, the relative pressure pulsation amplitude in the root region increased by more than 530%. Additionally, changes occur in the thickness of the water film in the erosion area on the working surface, disrupting the flow pattern and generating more vortices. This occurrence intensifies the relative pressure pulsation amplitude and reduces bucket stability. The study findings highlight the significant impact of sediment erosion on Pelton turbine pressure pulsation, posing a considerable risk to the unit's operational stability and safety.

Proteomic analysis revealing mechanisms of κ-carrageenan modulating the gelling properties of heat-induced microbial transglutaminase cross-linked myofibrillar protein gels

The effects of κ-carrageenan (KC, 0.2 %, w/w) on the gelling properties and microstructures of heat-treated myofibrillar protein (MP) gels mediated by various levels (0, 0.1, 0.3, and 0.5 %, w/w) of microbial transglutaminase (TG) were investigated. The results revealed that regardless of TG level, the existence of KC significantly promoted the forming of disulphide bonds but limited the generation of large-sized protein polymers in MP gel treated with TG alone, as well as subsequently enhanced the water retention ability and gel strength of mixed MP gel, especially in the sample adding 0.3% TG and 0.2% KC, which was clearly verified by the forming of more denser and continuous gel network. Moreover, TG-induced changes in protein structure led to the alteration in the protein profiles of different MP gels, and an obvious down-regulation trend of myosin (Q9TV63, Q9TV62, P79293, and Q9TV61) was identified in the TG-0.3 group. Furthermore, liquid chromatography–tandem mass spectrometry analysis demonstrated that TG mainly induces protein crosslinking in the light meromyosin domain of the myosin rod. Meanwhile, in the presence of KC, the crosslinking-site percentage of the TG-0.3 group decreased from 37.7% to 36.2%, indicating that KC potentially reduces TG-induced crosslinking in MP gels. Thus, our findings illustrate the critical mechanisms underlying the modulation of KC on the gelling properties of TG-mediated MP gels at the molecular level, which providing potential guideline for the combined applications of TG and KC in the meat industry.

Comparative Study of Coagulation Profile and Haematological Parameters in Pregnancy-Induced Hypertension (PIH).

Background Pregnancy-induced hypertension (PIH) is a major cause of maternal and fetal morbidity and mortality. PIH, including gestational hypertension, pre-eclampsia, and eclampsia, often leads to significant alterations in coagulation profiles and haematological parameters, posing risks for thromboembolic and haemorrhagic complications. This study aimed to compare the coagulation and haematological parameters between women with PIH and normotensive pregnant women. Methods A cross-sectional observational study was conducted on 110 pregnant women, divided into two groups: 55 with PIH and 55 with normotensives. Coagulation markers such as prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), and platelet count were measured. Bleeding and clotting times were also evaluated. Data were statistically analysed using student's t-test and chi-square tests, with p ≤ 0.05 considered significant. Results Women with PIH exhibited significantly lower platelet counts, PT, aPTT, and INR values compared to the normotensive group (p < 0.0001). Thrombocytopenia and prolonged bleeding time were more common in the PIH group, suggesting an increased risk of both bleeding and clotting complications. Proteinuria was observed in 32 women (58.18%) in the PIH group, reflecting the severity of the disease. Additionally, the PIH group had markedly elevated blood pressure levels. Conclusion PIH is associated with significant coagulation and haematological abnormalities, including thrombocytopenia and a hypercoagulable state, which increase the risk of thromboembolic and hemorrhagic events. Routine monitoring of coagulation profiles and haematological parameters in PIH patients is essential for timely interventions and improving maternal and fetal outcomes.

Development of innovations for neighborhood care-Contribution of social innovation laboratories

The article demonstrates the contributions of the innovation program "D-Care Lab Baden-Württemberg 2023" to the development of innovative solutions for neighborhood care. The effects of the program are reconstructed on the basis of initial research findings pertaining to the innovation program. Adistinctive aspect of the laboratory is its cross-sectoral collaborative structure. The levels of impact can be defined as follows: the acquisition of skills by the participants, the connection between skills acquisition and learning arrangement, the changes observed as aresult of participation and the innovative solutions developed for care in the neighborhood. The initial results are presented in accordance with the theoretical research design and research methods previously outlined. The results demonstrate alterations in the competence profiles of the participants and the impact of the cooperative laboratory setting on the development of solutions. Based on these findings, the function of innovation programs becomes evident, thereby highlighting the necessity for mid-term to long-term impact analysis.

Association between alterations in the expanded lymphoid profileby flow cytometry and inborn errors of immunity

To evaluate the association between the expanded lymphoid profile and inborn errors of immunity using flow cytometry. Observational and cross-sectional, case-control study, carried out in patients with a diagnosis or clinical suspicion of inborn errors of immunity, treated at the Santísima Trinidad Children's Hospital in Córdoba, Argentina, from August 2021 to November 2022. Clinical data were collected, and peripheral blood samples were obtained for flow cytometry analysis, using the PIDOT tube, to identify lymphocyte subpopulations. For statistical analysis, Fisher's exact test, odds ratio and binary logistic regression model were used. 40 cases and 20 controls were analyzed. The most frequently altered lymphocyte subpopulations were: CD4+ n (63%), Mem c/s (60%) and Mem s/s (55%). A statistically significant association was found between several lymphocyte subpopulations and health-disease status. Binary logistic regression reported Mem s/s and CD4+n as altered lymphocyte subpopulations with a greater probability to have inborn errors of immunity. This study contributes to improving the understanding of inborn errors of immunity and demonstrates a strong association with altered lymphocyte subpopulation profiles. Mem s/s and CD4+n emerge as relevant biomarkers for diagnosis. Heterogeneity in different diseases and in flow cytometry underlines the importance of evaluating each patient individually, to improve diagnosis and treatment.

Solubilized β-Glucan Supplementation in C57BL/6J Mice Dams Augments Neurodevelopment and Cognition in the Offspring Driven by Gut Microbiome Remodeling.

A maternal diet rich in dietary fiber, such as β-glucan, plays a crucial role in the offspring's acquisition of gut microbiota and the subsequent shaping of its microbiome profile and metabolome. This in turn has been shown to aid in neurodevelopmental processes, including early microglial maturation and immunomodulation via metabolites like short chain fatty acids (SCFAs). This study aimed to investigate the effects of oat β-glucan supplementation, solubilized by citric acid hydrolysis, from gestation to adulthood. Female C57BL/6J mice were orally supplemented with soluble oat β-glucan (ObG) or carboxymethyl cellulose (CMC) via drinking water at 200 mg/kg body weight during breeding while the control group received 50 mg/kg body weight of carboxymethyl cellulose. ObG supplementation increased butyrate production in the guts of both dams and 4-week-old pups, attributing to alterations in the gut microbiota profile. One-week-old pups from the ObG group showed increased neurodevelopmental markers similar to four-week-old pups that also exhibited alterations in serum markers of metabolism and anti-inflammatory cytokines. Notably, at 8 weeks, ObG-supplemented pups exhibited the highest levels of spatial memory and cognition compared to the control and CMC groups. These findings suggest a potential enhancement of neonatal neurodevelopment via shaping of early-life gut microbiome profile, and the subsequent increased later-life cognitive function.

BOS-318 treatment enhances elexacaftor-tezacaftor-ivacaftor (ETI)-mediated improvements in airways hydration and mucociliary transport

BackgroundCFTR triple modulator therapy, elexacaftor-tezacaftor-ivacaftor (ETI) has transformed care for people with cystic fibrosis (pwCF) who have eligible mutations. It is, however, not curative. Response to treatment also varies and lung disease although slowed, remains progressive. We have previously demonstrated that inhibition of the epithelial sodium channel (ENaC) by selective furin inhibition offers an alternative, mutation-agnostic approach to enhance airways hydration and restore mucociliary transport (MCT) in CF. Inhibition of furin therefore, offers a potential therapeutic strategy for those ineligible, intolerant or non-responsive to ETI and may provide a further opportunity for clinical benefit for those currently treated with ETI. The aim of this study was to determine the impact of furin inhibition on ETI responses to assess its utility as an adjunct therapy.MethodsDifferentiated primary human CF bronchial epithelial cells (CF HBECs) were treated with the highly selective furin inhibitor, BOS-318 and ETI. Ion channel function was measured using a 24-channel Transepithelial Current Clamp (TECC-24) system and airways surface hydration was investigated by measuring airway surface liquid (ASL) height and MCT rate.ResultsThe presence of BOS-318 had no effect on the ability of ETI to stimulate CFTR-mediated Cl−secretion but contributed a reduced Na+transportviarobust inhibition of ENaC. This altered ion transport profile effected an improved ASL height and MCT rate which were significantly greater than improvements observed with ETI alone, demonstrating the benefits of the dual approach.ConclusionsSelective furin inhibition has potential to further improve clinical outcomes for all pwCF and offers opportunity as an adjunct to improve responses to currently available CFTR modulator therapies.

Altered gut microbial profile accompanied by abnormal short chain fatty acid metabolism exacerbates nonalcoholic fatty liver disease progression

Dysregulation of the gut microbiome has associated with the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). To determine the diagnostic capacity of this association, we compared fecal microbiomes across 104 participants including non-NAFLD controls and NAFLD subtypes patients that were distinguished by magnetic resonance imaging. We measured their blood biochemical parameters, 16 S rRNA-based gut microbiota and fecal short-chain fatty acids (SCFAs). Multi-omic analyses revealed that NAFLD patients exhibited specific changes in gut microbiota and fecal SCFAs as compared to non-NAFLD subjects. Four bacterial genera (Faecalibacterium, Subdoligranulum, Haemophilus, and Roseburia) and two fecal SCFAs profiles (acetic acid, and butyric acid) were closely related to NAFLD phenotypes and could accurately distinguish NAFLD patients from healthy non-NAFLD subjects. Twelve genera belonging to Faecalibacterium, Subdoligranulum, Haemophilus, Intestinibacter, Agathobacter, Lachnospiraceae_UCG-004, Roseburia, Butyricicoccus, Actinomycetales_unclassified, [Eubacterium]_ventriosum_group, Rothia, and Rhodococcus were effective to distinguish NAFLD subtypes. Of them, combination of five genera can distinguish effectively mild NAFLD from non-NAFLD with an area under curve (AUC) of 0.84. Seven genera distinguish moderate NAFLD with an AUC of 0.83. Eight genera distinguish severe NAFLD with an AUC of 0.90. In our study, butyric acid distinguished mild-NAFLD from non-NAFLD with AUC value of 0.83. And acetic acid distinguished moderate-NAFLD and severe-NAFLD from non-NAFLD with AUC value of 0.84 and 0.70. In summary, our study and further analysis showed that gut microbiota and fecal SCFAs maybe a method with convenient detection advantages and invasive manner that are not only a good prediction model for early warning of NAFLD occurrence, but also have a strong ability to distinguish NAFLD subtypes.

Pan-cancer analysis of the immunological and oncogenic roles of ATAD2 with verification in papillary thyroid carcinoma.

ATAD2 (ATPase Family AAA Domain-Containing 2) is highly expressed across varies tumor types, yet its common roles in tumor progression and immune interaction remain unclear. We analyzed the expression and alteration profiles of ATAD2, along with its diagnostic and prognostic role in pan-cancer, utilizing TCGA, GTEx, CPTAC, HPA, and cBioPortal databases. Furthermore, we examined the relationship between ATAD2 and immune infiltration utilizing single-cell sequencing data and TCGA database. Additionally, the expression and oncogenic functions of ATAD2 were verified in papillary thyroid carcinoma (PTC) through MTT, wound-healing, transwell, and flow cytometry assays. Our results revealed significant overexpression of ATAD2 in most cancers, strongly associated with poor prognosis. Amplification was the most frequent alteration type of ATAD2, with its mutation correlating with improved overall survival. ATAD2 was positively correlated with multiple inhibitory immune checkpoints and closely associated with the immunosuppressive microenvironment, particularly in PTC. In vitro experiments demonstrated that ATAD2 promoted the proliferation, migration, and invasion of PTC cells by activating the PI3K-AKT pathway and modulating the G1/S cell cycle checkpoint. Collectively, ATAD2 holds promise as a biomarker for pan-cancer diagnosis and prognosis, as well as a predictor of immunotherapeutic responsiveness and a therapeutic target to enhance the efficacy of existing anti-tumor immune therapies.

Quantification and evaluation of plasma free amino acid concentrations by LC-MS/MS after total gastrectomy

The effect of total gastrectomy (TG) on plasma free amino acid (PFAA) concentrations in patients with stage II gastric cancer was investigated in the study. Nineteen patients' plasma samples were collected before and three months post-gastrectomy, and PFAA levels were quantified using LC-MS/MS. For gradient elution of amino acids, the mobile phases (A: 3% formic acid-5% methanol-30 mM ammonium formate, B: acetonitrile) and a Hypersil C18 column (100 mm x 2.1 m, 1.9 µm) were used. The findings revealed substantial modifications in the profile of PFAA after TG. In particular, the concentrations of twenty amino acids increased significantly, including branched-chain amino acids, L-glutamate, L-alanine, L-methionine, glycine, L-cystine, and L-histidine. Conversely, L-arginine was also reduced statistically. These alterations in the PFAA profile indicate the favorable effects of TG on various physiological processes, such as enhanced immune function, improved tissue healing, and increased energy production. Investigating the effects of various surgical techniques on PFAA profiles is a promising approach for optimizing surgical procedures, improving metabolic function, increasing immunological responses, and improving overall quality of life. These findings highlight the significance of evaluating amino acid metabolism as an important part of treatment, given its potential to improve clinical outcomes and general well-being.

Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterised by impaired insulin secretion and action, often exacerbated by oxidative stress. Recent research has highlighted the intricate involvement of epigenetic mechanisms, particularly DNA methylation, in the pathogenesis of T2DM. This review aims to elucidate the role of DNA methylation as an epigenetic modifier in oxidative stress-mediated beta cell dysfunction, a key component of T2DM pathophysiology. Oxidative stress, arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defence mechanisms, is a hallmark feature of T2DM. Beta cells, responsible for insulin secretion, are particularly vulnerable to oxidative damage due to their low antioxidant capacity. Emerging evidence suggests that oxidative stress can induce aberrant DNA methylation patterns in beta cells, leading to altered gene expression profiles associated with insulin secretion and cell survival. Furthermore, studies have identified specific genes involved in beta cell function and survival that undergo DNA methylation changes in response to oxidative stress in T2DM. These epigenetic modifications can perpetuate beta cell dysfunction by dysregulating key pathways essential for insulin secretion, such as the insulin signalling cascade and mitochondrial function. Understanding the interplay between DNA methylation, oxidative stress, and beta cell dysfunction holds promise for developing novel therapeutic strategies for T2DM. Targeting aberrant DNA methylation patterns may offer new avenues for restoring beta cell function and improving glycemic control in patients with T2DM. However, further research is needed to elucidate the complex mechanisms underlying epigenetic regulation in T2DM and to translate these findings into clinical interventions.

Circulating proteomic profiles in women with morbid obesity compared to normal-weight women

In this study, we aimed to evaluate circulating proteomic levels in women with morbid obesity (MO) compared to normal-weight (NW) women. Moreover, we have compared the proteomic profile between women with metabolically healthy (MH) MO and those with type 2 diabetes mellitus (T2DM). The study included 66 normal-weight (NW) women and 129 women with MO (54 MH and 75 with T2DM). Blood samples were processed for proteomics, involving protein extraction, quantification, digestion with peptide labelling and Nano (liquid chromatography (LC)-(Orbitrap) coupled to mass/mass spectrometry (MS/MS) analysis. Statistical analyses were performed. We identified 257 proteins. Women with MO showed significantly increased levels of 35 proteins and decreased levels of 45 proteins compared to NW women. Enrichment analysis of metabolic pathways revealed significant findings. Women with MO have an altered proteomic profile compared to normal-weight women, involving proteins significantly related to chylomicron assembly, complement cascade, clotting pathways and the insulin growth factor system. Regarding women with MO and T2DM compared to MHMO women, the proteomic profile shows alterations in mostly the same pathways associated with obesity. These findings confirmed in previous reports can help us better understand the pathophysiology of obesity and associated diseases. SignificanceWomen with morbid obesity (MO) exhibit substantial proteomic alterations compared to normal-weight (NW) women, involving 80 proteins. These alterations are linked to significant metabolic pathways, including chylomicron assembly, complement cascade, clotting pathways and the insulin growth factor system. Additionally, women with MO and type 2 diabetes mellitus (T2DM) compared to metabolically healthy MO women share similar proteomic changes than the first comparison. These findings enhance our understanding of the pathophysiology of obesity and associated diseases, offering potential targets for therapeutic intervention.