Search Results (29)

Oropharyngeal dysphagia is prevalent in hospitalized geriatric and neurological populations and constitutes a major driver of disease-related malnutrition. Conventional texture-modified diets frequently rely on diluting solid foods with liquid agents to achieve safe swallowing consistency, a process that reduces caloric and protein density per gram and creates a so-called volume paradox, whereby large meal volumes deliver inadequate nutrients. This retrospective observational study, conducted at the Fondazione Policlinico Gemelli IRCCS in Rome, compared nutritional intake in 208 hospitalized dysphagic adults receiving either a traditional homogenized standard diet (THSD; n = 58) or a density-enriched dysphagia-prepared diet (DPD; n = 150). Following propensity-score matching, total daily energy intake was significantly higher with the DPD compared to the THSD (1024 ± 307 kcal vs. 523 ± 161 kcal; p < 0.0001), as was total protein intake (37.3 ± 12.9 g vs. 26.2 ± 12.7 g; p < 0.0001). Clinically meaningful differences were observed across all meal components, including a more than twofold advantage in breakfast protein content (6.6 ± 1.7 g vs. 3.0 ± 1.5 g). Despite these improvements, total energy and protein intake remained below estimated daily requirements in both groups, highlighting the need for systematic nutritional monitoring alongside catering optimization. These findings support density-enrichment as a practical and safe strategy for improving nutritional adequacy in dysphagic inpatients, with implications for reducing reliance on oral nutritional supplements and mitigating disease-related malnutrition in clinical settings. Full article

In this study, we investigated the genomic basis of key body measurement and weight traits in Iraqi Awassi sheep using a multi-locus genome-wide association approach. A total of 315 yearling animals were phenotyped for body length, chest depth, heart girth, withers height, and body weight, and genotyped using the Ovine 50K SNP BeadChip. Genome-wide association analyses were performed within the BLUPmrMLM framework to improve the detection of loci with moderate-to-small effects. Significant associations were identified using an LOD-based threshold (LOD ≥ 5), followed by positional annotation of nearby genes and functional enrichment analyses to infer their potential biological relevance. Multiple genomic regions were associated with the evaluated traits. Among the most biologically plausible candidate genes were DST and CFAP299 for body length, ADAMTS8 for chest depth, ZFPM1 and OST4 for heart girth, CPEB2 for body weight, and ITGBL1, RBMS3, and THSD7B for withers height. Functional enrichment analyses indicated the involvement of pathways related to integrin-mediated signaling, focal adhesion and integrin complexes, extracellular matrix organization, and post-transcriptional regulation, suggesting coordinated effects of cell–matrix interactions and gene-expression regulation on body size and conformation. Overall, these findings refine the genomic landscape underlying body weight and morphometric variation in Awassi sheep and provide a focused set of loci for future validation and possible application in marker-assisted and genomic selection programs. Full article

The development of males and females of the cephalopod Amphioctopus fangsiao is asynchronous. The male produces sperm after maturity for storage in a spermatophore prior to mating. After mating, the sperm enter the female spermatheca for storage until ovulation occurs, a period that lasts for 8 months. This is a biologically uncommon phenomenon because sperm cells generally fail to maintain their ability to fertilize for a long time after being ejaculated. However, the molecular mechanisms of this phenomenon are still not clear. Sperm cells are stored in the male spermatophore and the female spermatheca, each of which provides a suitable environment. To determine the molecular basis of the sperm storage mechanisms in A. fangsiao, protein profiles from spermathecal fluid and seminal plasma were characterized separately using mass spectrometry-based proteomics. The antioxidant enzymes superoxide dismutase (SOD), glutathione S-transferase (GST), and Thioredoxin (Trx), and the glycolytic enzymes lactate dehydrogenase (LDH), hexokinase (HK), pyruvate dehydrogenase kinase (PDK), and ATP synthase were significantly enriched in the spermathecal fluid. Catalase (CAT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase (TIM), phosphoglycerate kinase (PGK), and Chitinase were significantly enriched in the seminal plasma. The antimicrobial proteins transforming growth factor beta regulator 1 (TBRG1) and interleukin enhancer binding factor 2 (ILF2) and the extracellular matrix-related proteins transforming growth factor beta induced protein (TGFBIp) and thrombospondin type-1 domain-containing protein 4 (THSD4) were also significantly expressed in the spermathecal fluid. These proteins may be crucial for successful long-term sperm storage. We measured the activities of four antioxidant enzymes based on the proteomic results, supporting the antioxidant mechanism during the sperm storage process. This study enhances our understanding of the sperm storage ability of A. fangsiao. Full article

Fertility is key for calf production. Direct selection for female fertility under field conditions is hindered by low accuracy and selection response. An alternative widely implemented is selection for scrotal circumference (SC), genetically correlated with daughter fertility. This study performed a genome-wide association study (GWAS) to identify genomic regions and candidate loci linked to SC and female fertility in Retinta cattle. A multivariate ssGBLUP was applied using SC records from 1061 bulls, fertility-related traits from 59,254 females and genotypes from 1230 animals using the Axiom™ Bovine Genotyping v3 Array (65k). The ssGWAS revealed 23 1-Mb windows explaining >1% of additive genetic variance for SC, one on chromosome 2 and 22 on chromosome 3. Within these windows, 198 regions spanning 118 protein-coding genes and 80 RNA genes were identified. Several genes, including GSTM3, SPATA1, HFM1, and MSH4, were previously associated with male fertility. Six regions overlapped across male and female traits, containing two protein-coding genes (THSD7B and ENSBTAG00000021755). Identification of genomic markers linked to both female fertility and male SC enables selection of superior animals, improving reproductive efficiency and advancing knowledge of the genomic basis of male–female fertility relationships. Full article

Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) is a transmembrane protein increasingly recognized for its critical roles in vascular biology and disease pathogenesis. Initially identified as a marker of hematopoietic stem and endothelial cells during embryogenesis, THSD1 has since been implicated in a wide spectrum of physiological and pathological processes. This paper consolidates current knowledge on THSD1, with a focus on its roles in vascular integrity, perinatal disorders, and tumorigenesis. In vascular systems, THSD1 promotes focal adhesion assembly and suppresses autophagy-mediated adhesion turnover, thereby stabilizing endothelial attachment and maintaining barrier function. Genetic and functional studies support its protective role against intracranial aneurysms and hemorrhagic vascular disorders. THSD1 mutations have also been linked to perinatal disorders such as nonimmune hydrops fetalis and congenital vascular anomalies, suggesting a broader role in embryonic vascular patterning. Moreover, emerging evidence indicates that THSD1 acts as a tumor and metastasis suppressor, with potential anti-angiogenic properties, although its role in cancer remains to be fully defined. This paper not only consolidates existing knowledge but also identifies critical research gaps, providing a robust foundation for future investigations into the biology and clinical relevance of THSD1. Full article

Geese (Anser cygnoides) are popular worldwide with consumers for their unique meat quality, egg production, foie gras, and goose down; however, the key genes that influence geese growth remain elusive. To explore the mechanism of geese growth, a total of 500 Zhedong White geese were raised; four high-weight (HW) and four low-weight (LW) male geese were selected to collect carcass traits and for further transcriptomic and metabolomic analysis. The body weight and average daily gain of HW geese were significantly higher than those of the LW geese (p-value < 0.05), and the yields of the liver, gizzard, glandular stomach, and pancreas showed no significant difference between the HW and the LW group (p-value > 0.05). Compared with the LW geese, 19 differentially expressed genes (DEGs) (i.e., COL11A2, COL22A1, and TF) were detected in the breast muscle from the HW geese, which were involved in the PPAR signaling pathway, adipocytokine signaling pathway, fatty acid biosynthesis, and ferroptosis. A total of 59 differential accumulation metabolites (DAMs), which influence the pathways of glutathione metabolism and vitamin B6 metabolism, were detected in the breast muscle between the HW and LW geese. In the liver, 106 DEGs (i.e., THSD4, CREB3L3, and CNST) and 202 DAMs were found in the livers of the HW and LW groups, respectively. DEGs regulated the pathways of the TGF-beta signaling pathway, pyruvate metabolism, and adipocytokine signaling pathway; DAMs were involved in pyrimidine metabolism, nitrogen metabolism, and phenylalanine metabolism. Correlation analysis between the top DEGs and DAMs revealed that in the breast muscle, the expression levels of COL11A2 and COL22A1 were positively correlated with the content of S-(2-Hydroxy-3-buten-1-yl)glutathione. In the liver, the expression of THSD4 was positively correlated with the content of 2-Hydroxyhexadecanoic acid. In addition, one DEG (LOC106049048) and four DAMs (mogrol, brassidic acid, flabelline, and L-Leucyl-L-alanine) were shared in the breast muscle and liver. These important results contribute to improving the knowledge of goose growth and exploring the effective molecular markers that could be adopted for Zhedong White goose breeding. Full article

Membranous nephropathy (MN) is a disease with an etiology and pathogenesis that are still not fully understood, and it represents a great challenge. It is characterized by a variable course, spontaneous remissions and relapses. The inability to rely entirely on antibodies and the continuous threat of a malignant disease make the differentiation of MN types extremely difficult. Data of twelve patients with membranous nephropathy, ranging in age between 28 and 67 years, are presented; in total, seven men and five women were observed for a period of 2 to 10 years. In all patients, the diagnosis was confirmed through kidney biopsy and laboratory tests, including immunological, histopathological, and immunohistochemical tests. Histopathological and immunohistochemical tests were applied on available material from the thyroid gland in two patients and the gallbladder in two patients with MN. Data of 102 patients with MN and their comorbidities are evaluated in order to establish correlations. These and other data are used to build a hypothetical pathogenetic model that explains the etiology and the likely pattern of disease occurrence. We found a connection between chronic cholecystitis, thyroiditis, hepatitis, and other diseases in the occurrence of MN and disease course. From our practice and cases, we drew the conclusion that chronic inflammation in sites that express PLA2R leads to the formation of antibodies against PLA2R. These antibodies occur as a preformed immune complex or separately and are deposited in the subepithelial space, leading to MN appearance. Full article

Genetic variants related to susceptibility to chronic respiratory conditions such as interstitial lung disease (ILD) could share critical pathways in the pathogenesis of COVID-19 and be implicated in COVID-19 outcomes and post-COVID-19. We aimed to identify the participation of genetic variants in lung function and ILD genes in severe COVID-19 outcomes and post-COVID-19 condition. We studied 936 hospitalized patients with COVID-19. The requirement of invasive mechanical ventilation (IMV) and the acute respiratory distress syndrome (ARDS) classification were considered. The mortality was assessed as the in-hospital death. The post-COVID-19 group included 102 patients evaluated for pulmonary function tests four times during the year after discharge. Five variants (FAM13A rs2609255, DSP rs2076295, TOLLIP rs111521887, TERT rs2736100, and THSD4 rs872471) were genotyped using TaqMan assays. A multifactor dimensionality reduction method (MDR) was performed for epistasis estimation. The TERT rs2736100 and THSD4 rs872471 variants were associated with differential risk for ARDS severity (moderate vs. severe, CC + CA, p = 0.044, OR = 0.66, 95% CI = 0.44–0.99; and GG p = 0.034, OR = 2.22, 95% CI = 1.04–4.72, respectively). These variants and FAM13A rs2609255 were also related to pulmonary function post-COVID-19. The MDR analysis showed differential epistasis and correlation of the genetic variants included in this study. The well-known variants in recognized genes related to pulmonary function worsening and interstitial disorders are related to the severity and mortality of COVID-19 and lung performance in the post-COVID-19 condition. Full article

Background/Objectives: Autoimmunity towards podocyte antigens causes membranous nephropathy (MN). Numerous MN target antigens (MNTAgs) have been reported, including PLA2R1, THSD7A, NTNG1, TGFBR3, HTRA1, NDNF, SEMA3B, FAT1, EXT1, CNTN1, NELL1, PCDH7, EXT2, PCSK6, and NCAM1, but their podocyte expression has not been thoroughly studied. Methods: We screened CZ CELLxGene single-cell RNA (scRNA) sequence datasets for those of adult, fetal, and mouse kidneys and analyzed the above MNTAgs’ expression. Results: In adult kidneys, most MNTAgs are present in podocytes, except PCSK6 and NCAM1. PLA2R1 is expressed significantly more than other MNTAgs in podocytes and is a major podocyte marker, consistent with PLA2R1 as the dominant MNTAg. Additionally, PLA2R1 is a top-upregulated gene in the podocytes of chronic kidney disease, acute kidney injury, and diabetic nephropathy, indicating its general role in causing podocyte injury. PLA2R1, NTNG1, HTRA1, and NDNF display podocyte-enriched expression along with elevated chromatin accessibility in podocytes, suggesting transcription initiation contributing to their preference expression in podocytes. In the fetal kidney, most MNTAgs are expressed in podocytes. While PLA2R1 is weakly present in podocytes, SEMA3B is abundantly expressed in immature and mature podocytes, supporting SEMA3B as a childhood MNTAg. In mouse kidneys, Thsd7a is the only MNTAg with a prominent level and podocyte-specific expression. Conclusions: Most MNTAgs are present in podocytes in adults and during renal development. In adults, PLA2R1 expression is highly enriched in podocytes and significantly upregulated in multiple kidney diseases accompanied by proteinuria. In mouse kidneys, Thsd7a is specifically expressed in podocytes at an elevated level. Full article

The differentiation between primary and secondary forms of membranous nephropathy (MN) is a cornerstone that is necessary for adequate decision making regarding the treatment options and behavior of each specific case. Kidney biopsy and antibody results can be controversial, and a unique biomarker has still not been found. Background and Objectives: We investigated the lack of mannose-binding lectin (MBL) deposition in patients with secondary MNs (sMNs) with the presence of IgG4 deposition in relation to the presence of MBL deposition in patients with primary MNs (pMNs). We also established a connection between the stage of MN and MBL deposition. Materials and Methods: Materials from 72 renal biopsies with proven MN were used for immunohistochemistry staining (IHC) for the phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4, and MBL. Patients were separated into one of the following three groups: primary MN (pMN), idiopathic MN (iMN), and secondary MN (sMN). Serum antibodies for PLA2R and thrombospondin type-I-domain-containing 7A (THSD7A) were also used for the precise evaluation of the type of MN, as well as for detecting positivity for PLA2R using IHC. Which stage of MN was present in relation to the deposition of MBL was evaluated. Results: In total, 50 patients were positive for IgG4, 34 with pMN, 12 with iMN, and 4 with sMN. A total of 20 patients were positive for MBL, 14 with pMN and 6 with iMN; no MBL deposits were found in patients with sMN. MBL positivity was predominantly present in the first two stages of MN, with a gradual reduction in the later stages. Conclusions: The activation of the lectin–complement pathway occurs in the early stages of the disease and is associated with the deposition of IgG4; IgG4 deposition is present in sMN, but there is no MBL deposition. IgG4 cannot be used for the differentiation of primary from secondary MNs, but the lack of MBL can be used as a marker for sMN in the early stages of the disease. Full article

Lung cancer is the leading cause of cancer-related deaths in the western world. Squamous cell carcinoma is one of the most common histological subtypes of this malignancy. For squamous cell carcinoma of the lung (LSCC), prognostic and predictive markers still are largely missing. In a previous study, we were able to show that the expression of THSD7A shows an association with unfavorable prognostic parameters in prostate cancer. There is also a link to a high expression of FAK. There is incidence that SCARA5 might be the downstream gene of THSD7A. Furthermore, there is evidence that SCARA5 interacts with FAK. We were interested in the role of SCARA5 as a potential biomarker in LSCC. Furthermore, we wanted to know whether SCARA5 expression is linked to THSD7A positivity and to the expression level of FAK. For this reason, we analyzed 101 LSCC tumors by immunohistochemistry. Tissue microarrays were utilized. No significant association was found between SCARA5 expression and overall survival or clinicopathological parameters. There was also no significant association between THSD7A positivity and SCARA5 expression level. Moreover, no significant association was found between FAK expression level and SCARA5 expression level. SCARA5 seems not to play a major role as a biomarker in squamous cell carcinoma of the lung. Full article

Membranous nephropathy constitutes approximately 20% of adult nephrotic syndrome cases. In approximately 80% of cases, membranous nephropathy is primary, mediated by IgG autoantibodies primarily targeting podocyte antigens (PLA2R, THSD7A, etc.). The treatment involves a combination of corticosteroids and cyclophosphamide or anti-CD20-based therapies, e.g., rituximab. In the event of significant proteinuria and in order to avoid the urinary elimination of rituximab, therapeutic apheresis, in particular semi-specific immunoadsorption, may be an option allowing for a reduction in proteinuria and autoantibodies before initiating treatment with rituximab. We present the preliminary experience of three patients treated with semi-specific immunoadsorption for primary membranous nephropathy between January 2021 and March 2023. Two patients were anti-PLA2R-autoantibody-positive and one was seronegative. The average age was 59 ± 17 years. Semi-specific immunoadsorption did not reduce albuminuria, but it, nevertheless, led to an increase in serum albumin, contributing to the regression of edema. It effectively eliminated anti-PLA2R autoantibodies in the two anti-PLA2R-positive patients. Consequently, apheresis may not induce a rapid reduction in proteinuria, but could contribute to a more accelerated remission when combined with the anti-CD20 treatment. Full article

Focal adhesions (FAs) play a crucial role in cell spreading and adhesion, and their autophagic degradation is an emerging area of interest. This study investigates the role of Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) in regulating autophagy and FA stability in brain endothelial cells, shedding light on its potential implications for cerebrovascular diseases. Our research reveals a physical interaction between THSD1 and FAs. Depletion of THSD1 significantly reduces FA numbers, impairing cell spreading and adhesion. The loss of THSD1 also induces autophagy independently of changes in mTOR and AMPK activation, implying that THSD1 primarily governs FA dynamics rather than serving as a global regulator of nutrient and energy status. Mechanistically, THSD1 negatively regulates Beclin 1, a central autophagy regulator, at FAs through interactions with focal adhesion kinase (FAK). THSD1 inactivation diminishes FAK activity and relieves its inhibitory phosphorylation on Beclin 1. This, in turn, promotes the complex formation between Beclin 1 and ATG14, a critical event for the activation of the autophagy cascade. In summary, our findings identify THSD1 as a novel regulator of autophagy that degrades FAs in brain endothelial cells. This underscores the distinctive nature of THSD1-mediated, cargo-directed autophagy and its potential relevance to vascular diseases due to the loss of endothelial FAs. Investigating the underlying mechanisms of THSD1-mediated pathways holds promise for discovering novel therapeutic targets in vascular diseases. Full article

Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis “prostate cancer”. For this reason, it is desirable to find novel prognostic and predictive markers. In former studies, we showed that THSD7A expression is associated with unfavorable prognostic parameters in prostate cancer and is linked to a high expression of focal adhesion kinase (FAK). Recently, scavenger receptor class A member 5 (SCARA5) was reported to be the downstream gene of THSD7A in esophageal squamous cell carcinoma. SCARA5 is believed to play an important role in the development and progression of several different tumor types. Most studies describe SCARA5 as a tumor suppressor. There is also evidence that SCARA 5 interacts with FAK. To examine the role of SCARA5 as a potential biomarker in prostate cancer, a total of 461 prostate cancers were analyzed via immunohistochemistry using tissue microarrays. Furthermore, we compared the expression level of SCARA5 with our previously collected data on THSD7A and FAK. High SCARA5 expression was associated with advanced tumor stage (p < 0.001), positive nodal status (p < 0.001) and high Gleason-score (p < 0.001). At least, strongly SCARA5-positive cancers were associated with THSD7A-positivity. There was no significant association between SCARA5 expression level and FAK expression level. To our knowledge, we are the first to investigate the role of SCARA5 in prostate cancer and we demonstrated that SCARA5 might be a potential biomarker in prostate cancer. Full article