Tissues Of Individuals Research Articles

Obesity is associated with adverse outcomes in primary immune thrombocytopenia - a retrospective single-center study

The pathophysiology of immune thrombocytopenia (ITP) involves immune-mediated platelet destruction. The presence of adipose tissue in obese individuals creates an inflammatory environment that could potentially impact the clinical course and outcomes of ITP. However the relationship between obesity and ITP outcomes has not been well described. We evaluated ITP outcomes in 275 patients diagnosed with primary ITP from 2012 to 2022. Patients were categorized into four groups based on their body mass index (BMI) at diagnosis. Female gender was associated with a lower platelet count at the time of diagnosis at any BMI. Patients with high BMI had lower platelet counts at diagnosis and at platelet nadir (p < 0.001), an increased likelihood of requiring therapy (p < 0.001) and requiring multiple lines of therapy (p = 0.032). Non-obese patients who required corticosteroid treatment experienced a longer remission duration compared to obese patients (p = 0.009) and were less likely to be steroid-dependent (p = 0.048). Our findings suggest that obesity may be a significant risk factor for developing ITP and for ITP prognosis. Future studies are needed to evaluate the role of weight loss intervention in improving ITP outcomes.

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome.

Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

Histological and morphometric specifics of the jaw alveolar process bone tissue in individuals with connective tissue dysplasia symptoms

Цель исследования. Изучение гистоморфометрических особенностей в костной ткани и сосудистой системе челюстей у лиц с синдромом недифференцированной дисплазии соединительной ткани (НДСТ) для повышения эффективности патоморфологической диагностики врожденных нарушений развития соединительной ткани (СТ).Материал и методы. Гистологические и морфометрические исследования костных препаратов выпол- нены на секционном материале 34 паспортизированных субъектов в возрасте 36–60 лет с сохраненными зубными рядами на нижней челюсти. Исследование проводились в зонах в проекции 36 и 46 зубов с из- учением надкостницы, компактного и губчатого слоев кости. Субъекты были распределены в 2 группы: 1-я группа (n=15) – без фоновой патологии, 2-я группа (n=19) – с синдромом НДСТ при наличии не менее 6 локомоторных и локомоторно-висцеральных признаков с поражением не менее 2–3 органов. При исследо- вании гистоструктуры препараты окрашивали гематоксилином и эозином, пикрофуксином по Ван-Гизону, при морфометрии количественных показателей костной ткани и сосудистой системы (доля компактного вещества, доля губчатого вещества, численность сосудов, число гаверсовых каналов, диаметр сосудов, диаметр гаверсовых каналов, толщина сосудистой стенки, доля остеобластов, доля остеоцитов, доля осте- окластов) применяли программу ImageJ.Результаты. Ухудшение качественных показателей гистоангиоархитектоники челюстей при НДСТ про- является наличием следующих изменений: участки с дезориентацией балочных структур, увеличенные и деформированные остеоциты с расположенными в периферических отделах ядрами, дистрофические изменения остеоцитов, обеднение клеточного состава и сосудистого рисунка, увеличение объема вне- клеточного матрикса, расширение Гаверсовых остеонов, мультипликации и извитости сосудистого русла, очаги аутолитического рассасывания по типу пазушной резорбции, утолщения, искривления, нарушения пространственных взаимоотношений коллагеновых волокон, тонкостенные вены с резко увеличенным диаметром, утолщение стенок артериальных сосудов при уменьшении их просвета, участки венозной мальформации, сосуды с признаками эндотелиоза. Количественные изменения у субъектов с синдромом НДСТ по сравнению с данными у лиц без фоновой патологии реализуются следующими показателями (по Ме): снижением доли компактного вещества (в 2,14 раза), увеличением содержания губчатого вещества (в 1,42 раза), сокращением числа кровеносных сосудов (в 1,56 раза) при уменьшении их диаметра (в 1,54 раза), повышением толщины сосудистой стенки (в 2,27 раза), снижением числа гаверсовых каналов (в 1,44 раза) при увеличении их диаметра (в 2,25 раза), повышением доли остеобластов (в 3,54 раза), снижением содержания остеоцитов (в 1,78 раза).Заключение. Установленные изменения морфологии и микроангиоархитектоники челюстных костей у лиц с синдромом НДСТ свидетельствуют о незавершенности процессов «созревания» костных структур челюстно-лицевой области, прогрессировании свойственных для остеопороза дегенеративных и склероти- ческих изменений, замедлении регионарного микрокровотока, отображая специфику метаболизма СТ при коллагенопатиях. Целесообразно пересмотреть комплекс лечебно-профилактических и реабилитационных мероприятий у больных данной категории в сторону метаболической коррекции остеопении для повышения минеральной насыщенности и твердости костной ткани.

The microbiome landscape of early-onset colorectal cancer: A systematic review.

e15646 Background: The rise of early-onset colorectal cancer (EOCRC, age &lt; 50 years old) necessitates the examination of potential risk factors to enhance prevention and control strategies. Microbial dysbiosis has been hypothesized as a potential contributor, yet studies are limited. To guide future research, we systematically reviewed studies of the EOCRC microbiome, emphasizing methodological heterogeneities. Methods: We systematically reviewed available literature for microbiome studies involving EOCRC and synthesized findings according to comparison groups (healthy/later-onset CRC [LOCRC]), sample type (fecal /tumor), and analyses (taxonomic/metabolomic). Results: Collection, storage, extraction, and analytical methods varied across the 10 studies included out of 2073 studies. There were 377 unique EOCRC patients, of which most originated from China (193 EOCRC cases), the United States (52 EOCRC cases), and Japan (42 EOCRC cases). Six studies analyzed 224 unique EOCRC fecal samples (4 performed 16S, 5 performed WGSS, 4 performed metabolomic); five compared EOCRC against healthy individuals and five to LOCRC. Four studies utilized 153 unique EOCRC tumor samples (3 performed 16S, 1 performed WGSS, 1 performed metabolomic); two compared with tumor-adjacent normal tissue, one to colonic tissue of healthy individuals, and four to LOCRC. Among studies comparing fecal samples of EOCRC to healthy individuals, EOCRC exhibited increased levels of Fusobacterium and Escherichia-Shigella, known for metabolizing 5-Fluorouracil, while butyrate-producing taxa like Faecalibacterium, protective against CRC, were diminished; EOCRC also showed decreased lung-associated pathogens and Clostridium difficile, but increased oral pathogens. Among studies comparing fecal samples of EOCRC to LOCRC, EOCRC fecal samples were more abundant in oral/gastrointestinal pathogens, with varying findings on Fusobacterium nucleatum. Faecalibacterium prausnitzii was more abundant in EOCRC than LOCRC, whereas Escherichia-Shigella was less abundant. Fecal metabolomic studies displayed increased LPS-related pathways and bile acids in EOCRC compared to healthy individuals. Compared to tumor-adjacent normal tissues or colonic tissues of healthy individuals, EOCRC tumors were characterized by higher levels of Fusobacterium, Actinomyces, and Escherichia coli ( E. coli), fewer butyrate producers, and more Bacteroides fragilis. Conclusions: While data is limited and methodologies varied, emerging evidence suggests that EOCRC may have unique microbial signatures compared to both healthy individuals and LOCRC. This may signal unique pathogenesis for EOCRC and present potential for prevention, early detection, and intervention. It is essential to harmonize study methods and analytical approaches to advance understanding of the role of microbiome in EOCRC.

MiR-653-5p drives osteoarthritis pathogenesis by modulating chondrocyte senescence

BackgroundDue to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression.MethodsWe screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus.ResultsMiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice.ConclusionsMiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.

Ductal carcinoma in situ develops within clonal fields of mutant cells in morphologically normal ducts.

Mutations are abundantly present in tissues of healthy individuals, including the breast epithelium. Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field of mutant cells that is predisposed towards lesion formation. To study the clonal and spatial relationships between morphologically normal breast epithelium adjacent to pre-cancerous lesions, we developed a three-dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival, formalin-fixed breast tissue with the non-obligate breast cancer precursor ductal carcinoma in situ (DCIS). Using this 3D image-guided characterization method, we built high-resolution spatial maps of DNA copy number aberration (CNA) profiles within the DCIS lesion and the surrounding normal mammary ducts. We show that the local heterogeneity within a DCIS lesion is limited. However, by mapping the CNA profiles back onto the 3D reconstructed ductal subtree, we find that in eight out of 16 cases the healthy epithelium adjacent to the DCIS lesions has overlapping structural variations with the CNA profile of the DCIS. Together, our study indicates that pre-malignant breast transformations frequently develop within mutant clonal fields of morphologically normal-looking ducts. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Analysis of gene expression in the postmortem brain of neurotypical Black Americans reveals contributions of genetic ancestry

Ancestral differences in genomic variation affect the regulation of gene expression; however, most gene expression studies have been limited to European ancestry samples or adjusted to identify ancestry-independent associations. Here, we instead examined the impact of genetic ancestry on gene expression and DNA methylation in the postmortem brain tissue of admixed Black American neurotypical individuals to identify ancestry-dependent and ancestry-independent contributions. Ancestry-associated differentially expressed genes (DEGs), transcripts and gene networks, while notably not implicating neurons, are enriched for genes related to the immune response and vascular tissue and explain up to 26% of heritability for ischemic stroke, 27% of heritability for Parkinson disease and 30% of heritability for Alzheimer’s disease. Ancestry-associated DEGs also show general enrichment for the heritability of diverse immune-related traits but depletion for psychiatric-related traits. We also compared Black and non-Hispanic white Americans, confirming most ancestry-associated DEGs. Our results delineate the extent to which genetic ancestry affects differences in gene expression in the human brain and the implications for brain illness risk.

Molecular characterization, expression analysis and function identification of Pf_IL-12p35, Pf_IL-23p19 and Pf_IL-12p40 genes in yellow catfish (Pelteobagrus fulvidraco)

The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf_IL-12p35a/b, Pf_IL-23p19 and Pf_IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf_IL-12p35a/b and Pf_IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf_IL-12p35a/b and Pf_IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf_IL-12p40a mRNA was induced in gill, and Pf_IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf_IL-12p35a and Pf_IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf_IL-12 and rPf_IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf_IL-12 and Pf_IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development.

MIF inhibition attenuates intervertebral disc degeneration by reducing nucleus pulposus cell apoptosis and inflammation

Nucleus pulposus cells (NPCs) apoptosis and inflammation are the extremely critical factors of intervertebral disc degeneration (IVDD). Nevertheless, the underlying procedure remains mysterious. Macrophage migration inhibitory factor (MIF) is a cytokine that promotes inflammation and has been demonstrated to have a significant impact on apoptosis and inflammation. For this research, we employed a model of NPCs degeneration stimulated by lipopolysaccharides (LPS) and a rat acupuncture IVDD model to examine the role of MIF in vitro and in vivo, respectively. Initially, we verified that there was a significant rise of MIF expression in the NP tissues of individuals with IVDD, as well as in rat models of IVDD. Furthermore, this augmented expression of MIF was similarly evident in degenerated NPCs. Afterwards, it was discovered that ISO-1, a MIF inhibitor, effectively decreased the quantity of cells undergoing apoptosis and inhibited the release of inflammatory molecules (TNF-α, IL-1β, IL-6). Furthermore, it has been shown that the PI3K/Akt pathway plays a vital part in the regulation of NPCs degeneration by MIF. Ultimately, we showcased that the IVDD process was impacted by the MIF inhibitor in the rat model. In summary, our experimental results substantiate the significant involvement of MIF in the degeneration of NPCs, and inhibiting MIF activity can effectively mitigate IVDD.

Domestic dogs as environmental sentinel in comparative toxicologic pathology: Assessment of metals and rare earth elements concentrations in healthy and neoplastic mammary glands

Quantification of trace element concentrations in human and animal tissues has acquired great importance in the last few years, considering the pivotal role of these elements in several physiological and pathological processes. Variations in their concentrations appear to have a role in the development and advancement of diseases in both humans and animals, for example, cancer. The purpose of this study was to investigate the concentration of rare earth elements and metals in healthy and neoplastic Formalin-Fixed Paraffin-Embedded (FFPE) mammary gland tissue of dogs. All samples were processed to have a quantitative determination of inorganic elements including metals of known toxicological interest such as Pb, Cd, Tl, As, Hg, the trace elements Mn, Fe, Co, Cu, Zn, Se, and other elements including Cr, V, Mo, Ni, Sb, W, Sn. Moreover, rare earth elements (REEs) (Sc, Y, Lu, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb) were also investigated. Cu and Mo concentrations in mammary cancerous tissue were greater than those in normal mammary glands (p<0.05). In non-neoplastic tissue increased concentrations of Cd, Co, Ni, Tl, and V were also reported (p<0.05). The mammary tissue of healthy individuals had greater concentrations of REEs than the neoplastic mammary glands (p<0.05). The results of our study confirmed differences in mammary inorganic element concentrations between healthy and neoplastic groups, highlighting the potential relevance of these fluctuations in toxicologic pathology.

Subacromial bursa in patients with rotator cuff tear with or without adhesive capsulitis exhibits a differential transcriptome with potential molecular biomarkers

Subacromial bursa in patients with rotator cuff tear with or without adhesive capsulitis exhibits a differential transcriptome with potential molecular biomarkers

Sleeve Gastrectomy Reduces Oxidative Stress and Reverses Mitochondrial Dysfunction Associated with Metabolic Syndrome.

Previous studies have detected mitochondrial alterations in tissues of individuals with obesity and type 2 diabetes mellitus (T2DM). Metabolic surgery could be an effective treatment to improve mitochondrial morphology and reduce oxidative stress (OS). An experimental study was carried out using 48 male Wistar rats, divided into 6 groups (n = 8): control (C), induced Metabolic Syndrome (MS); intervention with sleeve gastrectomy (SG), MS + SG with 6weeks postoperatively (MS + SG6), MS + SG with 12weeks postoperatively (MS + SG12), and MS + SG with 24weeks postoperatively (MS + SG24). Biochemical markers indicative of MS (glycemia, cholesterol, and triglyceride levels) and oxidative stress markers (nitric oxide levels, Superoxide dismutase and Myeloperoxidase activity) were determined. To study mitochondrial morphology, tissue sections of the thoracic aorta, stomach, liver, heart, and kidney were observed by electron microscopy. MS group exhibited elevated glycemic values and dyslipidemia. SG and MS + SG groups showed improvements in glycemia and lipid profiles compared to MS. OS biomarkers indicated reduced oxidative stress in SG and MS + SG groups compared to MS. Electron microscopy revealed mitochondrial alterations in MS. SG group showed no changes compared to the control. MS + SG6 and MS + SG12 groups showed a recovery of mitochondrial morphology until reaching images similar to the control in MS + SG24. Metabolic surgery could improve mitochondrial function by restoring mitochondrial morphology and architecture and, consequently, reducing systemic oxidative stress and remitting associated metabolic alterations.

The Role of Sulfhydryl (Thiols) Groups in Oral and Periodontal Diseases.

The sulfhydryl (thiols) group of glutathione plays an important role in the neutralization of foreign organic compounds and the reduction in peroxides. The purpose of the study is to evaluate the concentration of sulfhydryl groups in the gingival tissue of healthy individuals and those with gingivitis or periodontitis, and to examine the differences between these groups. To assess the concentration of sulfhydryl groups (thiols) in the gingival tissue of healthy individuals and those with gingivitis or periodontitis, we used spectrophotometric analysis using dithionitrobenzoate (DTNB) as a reagent to measure the accessible sulfhydryl groups present in gingival tissue proteins. The sample was divided into three distinct groups: individuals with periodontal health, gingivitis, and periodontitis, and different indices were used to assess the periodontal status of the participants. Next, a statistical analysis was conducted to compare the concentrations of sulfhydryl groups among the different groups of patients. The results of this study showed significantly decreased levels of sulfhydryl (thiols) groups in gingival tissue from patients with gingivitis and periodontitis, compared with healthy people (control group). These results confirm the role of sulfhydryl (thiols) groups in defense against free radicals. They share a significant role in detoxification, signal transduction, apoptosis, and various other functions at the molecular level.

Influence of glucagon-like peptide-1 receptor agonists on fat accumulation in patients with diabetes mellitus and non-alcoholic fatty liver disease or obesity: A systematic review and meta-analysis of randomized control trials

This systematic review and meta-analysis aimed to comprehensively evaluate the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in individuals with diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) or obesity. A search of PubMed, Embase, and Web of Science until October 2023 identified 13 Randomized Controlled Trials (RCTs) meeting the inclusion criteria. Bias risk was assessed using the Cochrane risk-of-bias instrument. Statistical analysis utilized standard mean differences (SMD) in Review Manager 5.4. Heterogeneity and publication bias were assessed. This study used the protocol registered with the Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY2023110020). GLP-1RA treatment significantly reduced VAT (SMD -0.55, 95% CI [-0.90, -0.19]), SAT (SMD -0.59, 95% CI [-0.99, -0.19]), body weight (SMD -1.07, 95% CI [-1.67, -0.47]), and body mass index (BMI) (SMD -1.10, 95% CI [-1.74, -0.47]) compared to controls. Heterogeneity was observed for VAT (I2=79%, P<0.01), SAT (I2=73%, P<0.01), body weight (I2=82%, P<0.01), and BMI (I2=82%, P<0.01). No publication bias was detected for VAT (P=0.57) and SAT (P=0.18). GLP-1RA treatment improved fasting blood glucose (FBG), postprandial glucose (PPG), hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and fibrosis-4 (FIB-4). This meta-analysis highlights GLP-1RAs' potential to reduce fat accumulation, body weight, and BMI and improve glycemic control in individuals with diabetes mellitus and NAFLD or obesity. These findings supported using GLP-1RAs as promising therapeutic agents to address abnormal adipose tissue distribution and metabolic dysfunction.

Autonomous enzymatic synthesis of functional nucleic acids for sensitive measurement of long noncoding RNA in human lung tissues

Aberrant long noncoding RNA (lncRNA) expression is linked to varied pathological processes and malignant tumors, and lncRNA can serve as potential disease biomarkers. Herein, we demonstrate the autonomous enzymatic synthesis of functional nucleic acids for sensitive measurement of lncRNA in human lung tissues on the basis of multiple primer generation-mediated rolling circle amplification (mPG-RCA). This assay involves two padlock probes that act as both a detection probe for recognizing target lncRNA and a domain for producing complementary DNAzyme. Two padlock probes can hybridize with target lncRNA at different sites, followed by ligation to form a circular template with the aid of RNA ligase. The circular template can initiate mPG-RCA to generate abundant Mg2+-dependent DNAzymes that can specifically cleave signal probes to induce the recovery of Cy3 fluorescence. The inherent characteristics of ligase-based ligation reaction and DNAzymes endow this assay with excellent specificity, and the introduction of multiple padlock probes endows this assay with high sensitivity. This strategy can rapidly and sensitively measure lncRNA with a wide linear range of 1fM - 1nM and a detection limit of 678 aM within 1.5h, and it shows distinct advantages of simplicity and immobilization-free without the need of precise temperature control and tedious procedures of nanomaterial preparation. Moreover, it enables accurate measurement of lncRNA level in normal cells and malignant tumor cells as well as differentiation of lncRNA expressions in tissues of non-small cell lung cancer (NSCLC) patients and normal individuals, with promising applications in biomedical studies and disease diagnosis.

Multicausal disruption of complement system activity in schizophrenia: abnormal transcription of C4, complement control proteins and microglia specific genes in brain and blood

IntroductionThe synaptic pruning process is based on the joint action of the complement system and microglia. In schizophrenia, accumulating evidence support that abnormal synaptic pruning during adolescence may be due to an altered Complement system activity. While this hypothesis is supported by C4 overexpression in various brain regions of individuals with schizophrenia, such alterations should be replicated and extended to other brain regions. Moreover, transcriptional studies of genes encoding regulators of the complement system activity (complement control proteins, CCP) and microglia-specific genes are lacking. Furthermore, it remains unknown whether brain and peripheral expression of such genes are related.ObjectivesTo explore expression of C4 as well as 4 CCP encoding genes and 10 microglia-specific genes at the brain and peripheral levels in individuals with schizophrenia as compared to healthy controls.MethodsWe analyzed candidate gene expression from 9 Gene Expression Omnibus datasets obtained from 333 individuals with schizophrenia and 306 healthy controls (HC). We first compared expression of the candidate genes between individuals with schizophrenia and HC in postmortem brain samples from 7 different brain regions. Then, the same comparison was made in 4 different peripheral tissues.ResultsRegarding the complement system, we observed C4 overexpression in the DLPFC, parietal, temporal cortex and associative striatum of individuals with schizophrenia. We report distinct altered expression patterns of CCP genes in the DLPFC, hippocampus and cerebellum of individuals with schizophrenia. Only CD46 expression was altered in the blood of individuals with schizophrenia. Regarding microglia, we report an underexpression of several microglia-specific genes in the cerebellum, associative striatum, hippocampus and parietal cortex of individuals with schizophrenia vs. HC. At the peripheral level, we observed a mixed altered expression pattern in the whole blood of individuals with schizophrenia.ConclusionsFirstly, our results suggest that the CCP-mediated regulatory mechanisms of the Complement system are impaired in the brain of individuals with schizophrenia, potentially contributing to an excessive Complement system activity (CSA). Secondly, our results support the hypothesis of a widespread underexpression of microglia-specific genes in brain tissues of individuals with schizophrenia. Functionally, the observed transcriptional alterations may be related to the synaptic pruning impairment. Alternatively, they may translate a compensatory mechanism for neuroinflammation. In the whole blood, the altered transcriptional pattern may represent a potential peripheral signature of SZ.Disclosure of InterestNone Declared

Is fibroblast growth factor 11 (FGF11) a predictive marker for breast cancer?

The prognostic role of fibroblast growth factor 11 (FGF11) has only been reported in cancers such as nasopharyngeal carcinoma and prostate cancer. The role of FGF11 in breast cancer is not fully known. It was aimed to compare FGF11 expression levels in de novo metastatic hormone receptor-positive, human epidermal reseptor-2-negative breast tumor tissue and healthy breast tissue and investigate the effect of the FGF11 expression on survival in breast cancer patients. To determine the FGF11 expression rate, breast tumor tissue of breast cancer patients diagnosed by breast biopsy and healthy breast tissue of healthy individuals who underwent breast biopsy due to benign lesions were used. The study population included 38 breast cancer patients and 24 healthy controls. The number of patients with a FGF11 expression level score of 1 (15.8% vs 12.5%), score of 2 (18.4% vs 12.5%), and score of 3 (31.6% vs 0%) was significantly higher in the patient group compared to the healthy control group. The median overall survival and progression-free survival were numerically better in the group with a FGF11 expression score of 0 to 1 than the group with a FGF11 expression score of 2 and 3, but this difference was not statistically significant. FGF11 may be a predictive marker for breast cancer formation. Additionally, with new FGF11-targeted treatment agents to be developed, endocrine resistance may be reduced, and better survival results may be achieved in hormone receptor-positive, human epidermal reseptor-2-negative breast cancer.

Possible Anti-Obesity Role of Flavonoids Through Brown Adipose Tissue

Worldwide, the incidence of overweight and obesity is increasing day by day, and this makes the control of body weight and complications a primary health problem. Weight loss diet therapy has long been a primary role in the prevention and management of obesity. Evidence supporting the specific anti-obesity effects of certain nutrient components, in particular, polyphenolic compounds, are increasing, as well as a strategy to limit energy intake to achieve control of body weight. Active brown adipose tissue in adult individuals is gaining interest as a new and feasible target for controlling body weight by triggering and increasing energy expenditure. Flavonoids are one of the polyphenolic compounds that draw attention by regulating non-shivering thermogenesis. Although each flavonoid has its health benefits; many phytochemical compounds classified as flavonoids have an anti-obesity effect by regulating oxidation, synthesis, uptake, and transport of fatty acids. In this study, current studies on the therapeutic effect of flavonoids on obesity by regulating energy expenditure through various mechanisms of action in brown adipose tissue are reviewed.

Molecular mechanisms implicated in protein changes in the Alzheimer’s disease human hippocampus

This study aimed to elucidate the specific biochemical pathways linked to changes in proteins in the Alzheimer's disease (AD) human hippocampus. Our data demonstrate a constant rise in the expression of four proteins (VGF, GFAP, HSPB1, and APP) across all eleven studies. Notably, UBC was the most centrally involved and had increased expression in the hippocampus tissue of individuals with AD. Modified proteins in the hippocampal tissue were found to activate the innate immune system and disrupt communication across chemical synapses. Four hub proteins (CD44, APP, ITGB2, and APOE) are connected to amyloid plaques, whereas two hub proteins (RPL24 and RPS23) are related to neurofibrillary tangles (NFTs). The presence of modified proteins was discovered to trigger the activation of microglia and decrease the functioning of ribosomes and mitochondria in the hippocampus. Three significant microRNAs (hsa-miR-106b-5p, hsa-miR-17-5p, and hsa-miR-16-5p) and transcription factors (MYT1L, PIN1, and CSRNP3) have been discovered to improve our understanding of the alterations in proteins within the hippocampal tissues that lead to the progression of AD. These findings establish a path for possible treatments for AD to employ therapeutic strategies that specifically focus on the proteins or processes linked to the illness.

Highlighting the effects of high-intensity interval training on the changes associated with hypertrophy, apoptosis, and histological proteins of the heart of old rats with type 2 diabetes

T2DM is known to cause disturbances in glucose homeostasis and negative changes in the heart muscle, while aging and diabetes are recognized risk factors for CVD. Given this, our study aims to investigate a method for controlling and managing CVDs induced by T2DM in elderly populations. To achieve this, we categorized 40 rats into 5 groups, including HAD (n = 8), HA (n = 8), AD (n = 8), AHT (n = 8), and ADT (n = 8). The exercise protocol consisted of eight weeks of HIIT (three sessions per week) performed at 90–95% of maximal speed. Following cardiac tissue extraction, we assessed the levels of IGF-1, PI3K, and AKT proteins using Western blot technique, and analyzed the histopathological variations of the heart tissue using H&E, Sudan Black, and Masson’s trichrome tissue staining. The histological findings from our study demonstrated that T2DM had a significant impact on the development of pathological hypertrophy and fibrosis in the heart tissue of elderly individuals. However, HIIT not only effectively controlled pathological hypertrophy and fibrosis, but also induced physiological hypertrophy in the AHT and ADT groups compared to the HA and AD groups. Results from Sudan Black staining indicated that there was an increase in lipid droplet accumulation in the cytoplasm of cardiomyocytes and their nuclei in the HA and AD groups, while the accumulation of lipid droplets decreased significantly in the AHT and ADT groups. In both the AHT group and the ADT group, a single HIIT session led to a reduction in collagen fiber accumulation and fibrotic frameworks. Our research also revealed that diabetes caused a significant elevation in the levels of IGF-1, PI3K, and AKT proteins, but after eight weeks of HIIT, the levels of these proteins decreased significantly in the training groups. Overall, our findings suggest that HIIT may be a suitable non-pharmacological approach for improving histological and physiological changes in elderly individuals with T2DM. However, we recommend further research to examine the impact of HIIT training on both healthy and diseased elderly populations.