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The search for DNA polymorphisms useful for the genetic improvement of dairy farm animals has spanned more than 40 years, yielding relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing has been found in casein genes and in Show less

Breast cancer, when advancing to a metastatic stage, involves the liver, impacting over 50% of cases and significantly diminishing survival rates. Presently, a lack of tailored therapeutic protocols for breast cancer liver metastasis (BCLM) underscores the need for a deeper understanding of molecular patterns governing this complication. Therefore, by analyzing differentially expressed genes (DEGs) between primary breast tumors and BCLM lesions, we aimed to shed light on the diversities of this process. This research investigated breast cancer liver metastasis relapse by employing a comprehensive approach that integrated data filtering, gene ontology and KEGG pathway analysis, overall survival analysis, identification of the alteration in the DEGs, visualization of the protein-protein interaction network, Signor 2.0, identification of positively correlated genes, immune cell infiltration analysis, genetic alternation analysis, copy number variant analysis, gene-to-mRNA interaction, transcription factor analysis, molecular docking, and identification of potential treatment targets. This study's integrative approach unveiled metabolic reprogramming, suggesting altered Show less

Diabetic macular oedema (DMO) is a complication of diabetic retinopathy that can result in vision loss. The disease can impact different spheres of a patient's life, including physical and psychological health, work, and activities of daily living, entailing an important use of healthcare and non-healthcare resources. This study aimed to estimate the socio-economic burden of DMO in Spain. The burden of DMO was estimated from a societal perspective, per patient, year of treatment since diagnosis, and type of treatment. Four categories were considered: direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labour productivity losses (LPL), and intangible costs (IC) associated with loss of quality of life. Average annual costs were calculated by multiplying the resources used per patient by their corresponding unit price (or financial proxy). For a more accurate estimation, differences in resource use between treatments (intravitreal anti-vascular endothelial growth factor injections of ranibizumab or aflibercept, and intravitreal dexamethasone implants) and year since diagnosis (first, second, and third year or beyond) were considered and presented separately. The reference year for costs was 2021. The average annual costs of DMO in the first year of treatment after diagnosis was estimated at €18,774, €17,512, and €16,188 per patient treated with ranibizumab, aflibercept, and dexamethasone, respectively. This burden would be reduced to €15,783, €15,701, and €12,233 in the second year, and to €15,119, €15,043, and €12,790 in the third year, respectively. Diagnosis of DMO entails an additional one-off cost of €485. DHC accounted for the greatest proportion of total annual costs per patient, independent of the year, with LPL also making an important contribution to total costs. The socio-economic impact of DMO on patients, the healthcare system, and society at large is substantial. The constant increase in its prevalence accentuates the need for planning and implementation of healthcare strategies to prevent vision loss and reduce the socio-economic burden of the disease. Show less

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain. The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021. The mean annual cost of nAMD was estimated at €17,265, €15,403, and €14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of €744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year 1; 42% in year 2; 39% in year 3). Similarly, DNHC had an important contribution to the total costs (32% in year 1; 35% in year 2; 37% in year 3), followed by IC (20% in year 1; 23% in year 2; 24% in year 3), while the contribution of patients' LPL was minimal. This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression. Show less

The decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with the decidual tissue. While evidence indicates the participation of embryo-derived factors in crosstalk with the uterus, the extent of their impact on post-implantation decidual development requires further investigation. Here, we utilize transgenic mouse models to selectively eliminate primary trophoblast giant cells (pTGCs), the embryonic cells that interface with maternal tissue at the forefront. pTGC ablation impairs decidualization and compromises decidual interferon response and lipid metabolism. Mechanistically, pTGCs release factors such as interferon kappa (IFNK) to strengthen the decidual interferon response and lipoprotein lipase (LPL) to enhance lipid accumulation within the decidua, thereby promoting decidualization. This study presents genetic and metabolomic evidence reinforcing the proactive role of pTGC-derived factors in mobilizing maternal resources to strengthen decidualization, facilitating the normal progression of early pregnancy. Show less

This study aimed to compare the accuracy of IFN-τ stimulated gene abundance (ISGs) in peripheral blood mononuclear cells (PBMCs), CL blood perfusion by Doppler ultrasound (Doppler-US), plasma concentration of P4 on Day 21 and pregnancy-associated glycoproteins (PAGs) test on Day 25 after timed-artificial insemination (TAI) for early pregnancy diagnosis in dairy cows and heifers. Holstein cows (n = 140) and heifers (n = 32) were subjected to a hormonal synchronization protocol and TAI on Day 0. On Day 21 post-TAI, blood samples were collected for PBMC isolation and plasma concentration of P4. The CL blood perfusion was evaluated by Doppler-US. Plasma samples collected on Day 25 were assayed for PAGs. The abundance of ISGs (ISG15 and RSAD2) in PBMCs was determined by RT-qPCR. Pregnancy was confirmed on Days 32 and 60 post-TAI by B-mode ultrasonography. Statistical analyses were performed by ANOVA using the MIXED procedure and GLIMMIX in SAS software. The pregnancy biomarkers were used to categorize the females as having undergone late luteolysis (LL); early embryonic mortality (EEM); late embryonic mortality (LEM); or late pregnancy loss (LPL). The abundance of ISGs, CL blood perfusion by Doppler-US, and concentrations of P4 on Day 21, and PAGs test on Day 25 were significant (P < 0.05) predictors of early pregnancy in dairy cows and heifers. Dairy cows had a greater (P = 0.01) occurrence of LL than heifers, but there was no difference (P > 0.1) for EEM, LEM, and LPL in heifers compared to cows. Cows with postpartum reproductive issues had a greater (P = 0.008) rate of LEM and a lesser (P = 0.01) rate of LPL compared to cows without reproductive issues. In summary, the CL blood perfusion by Doppler-US had the highest accuracy and the least number of false negatives, suggesting it is the best predictor of pregnancy on Day 21 post-TAI. The PAGs test was the most reliable indicator of pregnancy status on Day 25 post-TAI in dairy heifers and cows. The application of machine learning, specifically the MARS algorithm, shows promise in enhancing the accuracy of predicting early pregnancies in cows. Show less

Cross-language studies suggest more similarities than differences in how dysarthria affects the speech of people with Parkinson's disease (PwPD) who speak different languages. In this study, we aimed to identify the relative contribution of acoustic variables to distinguish PwPD from controls who spoke varieties of two Romance languages, French and Portuguese. This bi-national, cross-sectional, and case-controlled study included 129 PwPD and 124 healthy controls who spoke French or Portuguese. All participants underwent the same clinical examinations, voice/speech recordings, and self-assessment questionnaires. PwPD were evaluated French-speaking and Portuguese-speaking individuals were distinguished from each other with over 90% accuracy by five acoustic variables (the mean fundamental frequency and the shimmer of the sustained vowel /a/ production, the oral diadochokinesis performance index, the relative sound level pressure and the relative sound pressure level standard deviation of the text reading). A distinct set of parameters discriminated between controls and PwPD: for men, maximum phonation time and the oral diadochokinesis speech proportion were the most significant variables; for women, variables calculated from the oral diadochokinesis were the most discriminative. Acoustic variables related to phonation and voice quality distinguished between speakers of the two languages. Variables related to pneumophonic coordination and articulation rate were the more effective in distinguishing PwPD from controls. Thus, our research findings support that respiration and diadochokinesis tasks appear to be the most appropriate to pinpoint signs of dysarthria, which are largely homogeneous and language-universal. In contrast, identifying language-specific variables with the speech tasks and acoustic variables studied was less conclusive. Show less

Glomerular deposition of monoclonal IgM, frequently in the form of intracapillary pseudothrombi, can be seen in Waldenström macroglobulinemia (WM) and type I cryoglobulinemia (CG). They are typically associated with plasma cell or B-lymphoid neoplasms, particularly lymphoplasmacytic lymphoma (LPL). While infection is a frequent trigger of mixed (type II and III) CG, its association with type I CG is uncommon. We report two cases in which striking lambda-chain-restricted IgM deposits and acute kidney injury (AKI) occurred in the setting of known or suspected systemic infections, with prompt resolution on treatment of the infection. Show less

An internationally uniform lymphoma classification is of fundamental importance for the comparability of clinical studies. There are currently 2 parallel classifications: the "International Consensus Classification" and the WHO-classification. Follicular lymphoma 3B is classified separately as follicular large cell lymphoma in WHO-HAEM5. The diagnostic criteria of lymphoplasmocytic lymphoma (LPL) have been adjusted, both classifications recommend molecular testing for MYD88 and CXCR4 mutations. There are no significant diagnostic changes in aggressive B-cell lymphomas. The ICC classify NLPBL and THRLBCL into the group of large B-cell lymphomas (LBCL). NLPHL/NLPBL-specific therapy must be considered, which differs greatly from the therapy of DLBCL, especially in the early stages. Peripheral T-cell lymphomas are a group of nodal T-cell lymphomas with a TFH phenotype and frequent mutations; peripheral T-cell lymphoma (NOS) is therefore a diagnosis of exclusion. Indolent T-cell lymphomas/lymphoproliferations of the GI tract are rare but must be differentiated from aggressive T-cell lymphomas. The WHO-HAEM5 also includes reactive/non-neoplastic lymph node lesions classified according to B or T cell predominance. Show less

Since domestication, both evolutionary forces and human selection have played crucial roles in producing adaptive and economic traits, resulting in animal breeds that have been selected for specific climates and different breeding goals. Pakistani goat breeds have acquired genomic adaptations to their native climate conditions, such as tropical and hot climates. In this study, using next-generation sequencing data, we aimed to assess the signatures of positive selection in three native Pakistani goats, known as milk production breeds, that have been well adapted to their local climate. To explore the genomic relationship between studied goat populations and their population structure, whole genome sequence data from native goat populations in Pakistan (n = 26) was merged with available worldwide goat genomic data (n = 184), resulting in a total dataset of 210 individuals. The results showed a high genetic correlation between Pakistani goats and samples from North-East Asia. Across all populations analyzed, a higher linkage disequilibrium (LD) level (- 0.59) was found in the Pakistani goat group at a genomic distance of 1 Kb. Our findings from admixture analysis (K = 5 and K = 6) showed no evidence of shared genomic ancestry between Pakistani goats and other goat populations from Asia. The results from genomic selection analysis revealed several candidate genes related to adaptation to tropical/hot climates (such as; KITLG, HSPB9, HSP70, HSPA12B, and HSPA12B) and milk production related-traits (such as IGFBP3, LPL, LEPR, TSHR, and ACACA) in Pakistani native goat breeds. The results from this study shed light on the structural variation in the DNA of the three native Pakistani goat breeds. Several candidate genes were discovered for adaptation to tropical/hot climates, immune responses, and milk production traits. The identified genes could be exploited in goat breeding programs to select efficient breeds for tropical/hot climate regions. Show less

Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 Show less

Lipoic acid (LA) is an essential cofactor in prokaryotic and eukaryotic organisms, required for the function of several multienzyme complexes such as oxoacid dehydrogenases. Prokaryotes either synthesize LA or salvage it from the environment. The salvage pathway in Show less

Tunable long persistent luminescence (LPL) phosphor materials have great potential for optoelectronic cryptographic applications. However, the mainstream techniques of modulating LPL generally have the characteristics of complex preparation processes, demanding crystal field environments, or expensive dopant ions, which restrict large-scale commercial application. Herein, we develop a simple, high-efficiency, and low-cost strategy to optimize the LPL of LiGaO Show less

Heterologous production of proteins in Escherichia coli has raised several challenges including soluble production of target proteins, high levels of expression and purification. Fusion tags can serve as the important tools to overcome these challenges. SUMO (small ubiquitin-related modifier) is one of these tags whose fusion to native protein sequence can enhance its solubility and stability. In current research, a simple, efficient and cost-effective method is being discussed for the construction of pET28a-SUMO vector. In order to improve the stability and activity of lysophospholipase from Pyrococcus abyssi (Pa-LPL), a 6xHis-SUMO tag was fused to N-terminal of Pa-LPL by using pET28a-SUMO vector. Recombinant SUMO-fused enzyme (6 H-S-PaLPL) works optimally at 35 °C and pH 6.5 with remarkable thermostability at 35-95 °C. Thermo-inactivation kinetics of 6 H-S-PaLPL were also studied at 35-95 °C with first order rate constant (k Show less

The practical applications for aqueous Zn ion batteries (ZIBs) are promising yet still impeded by the severe side reactions on Zn metal. Here, a lysozyme protective layer (LPL) is prepared on Zn metal surface by a simple and facile self-adsorption strategy. The LPL exhibits extremely strong adhesion on Zn metal to provide stable interface during long-term cycling. In addition, the self-adsorption strategy triggered by the hydrophobicity-induced aggregation effect endows the protective layer with a gap-free and compacted morphology which can reject free water for effective side reaction inhibition performance. More importantly, the lysozyme conformation is transformed from α-helix to β-sheet structure before layer formation, thus abundant functional groups are exposed to interact with Zn Show less

Organic afterglow materials have drawn increasing attention for their great potential in practical applications. Until now, most of them just show the lifetimes in milliseconds or seconds, while the realization of long persistent luminescence (LPL) lasting for minutes or even hours is difficult. In 2017, Adachi and Kabe successfully realize the LPL with a duration longer than 1 hour in a purely organic system, which can be even comparable to some excellent inorganic materials. However, partially for the unclear structure-property relationship, organic LPL materials are still rather scarce, especially for the stable ones in air or aqueous solution. In this review, we present the recent progress in organic LPL, mainly focusing on the material design strategy and internal mechanism. It is anticipated that the deep understanding can be beneficial for the further development of organic LPL materials with good stability in air and even aqueous phase. Show less

Laparoscopic lavage (LPL) has been suggested for treatment of non-feculent perforated diverticulitis. In this observational study, the surgical treatment of diverticular disease in Sweden outside prospective trials was investigated. This population-based study used the National Patient Register to identify all patients in Sweden with emergency admissions for diverticular disease, as defined by ICD codes from July 2014 to December 2020. Demographics, surgical procedures and outcomes were assessed. In addition, register data since 1997 were retrieved to assess co-morbidities, previous abdominal surgeries, and previous admissions for diverticular disease. Among 47 294 patients with emergency hospital admission, 2035 underwent LPL (427 patients) or sigmoid resection (SR, 1608 patients) for diverticular disease. The mean follow-up was 30.8 months. Patients selected for LPL were younger, healthier and with less previous abdominal surgery for diverticular disease than those in the SR group (P < 0.01). LPL was associated with shorter postoperative hospital stay (mean 9.4 versus 14.9 days, P < 0.001) and lower 30-day mortality (3.5% versus 8.7%, P < 0.001). Diverticular disease-associated subsequent surgery was more common in the SR group than the LPL group except during the first year (P < 0.001). LPL had a lower mortality rate during the study period (stratified HR 0.70, 95% c.i. 0.53-0.92, P = 0.023). Laparoscopic lavage constitutes a safe alternative to sigmoid resection for selected patients judged clinically to require surgery. Show less

Obesity has emerged as a prominent global health concern, with heat stress posing a significant challenge to both human health and animal well-being. Despite a growing interest in environmental determinants of obesity, very few studies have examined the associations between heat stress-related environmental factors and adiposity. Consequently, there exists a clear need to understand the molecular mechanisms underlying the obesogenic effects of heat stress and to formulate preventive strategies. This study focused on culturing porcine subcutaneous preadipocytes at 41.5 ℃ to induce heat stress, revealing that this stressor triggered apoptosis and fat deposition. Analysis demonstrated an upregulation in the expression of HSP70, BAX, adipogenesis-related genes (PPARγ, AP2, CEBPα and FAS), the p-AMPK/AMPK ratio and SIRT1, PGC-1α in the heat stress group compared to the control group (P < 0.05). Conversely, the expression of lipid lysis-related genes (ATGL, HSL and LPL) and Bcl-2 decreased in the heat stress group compared to the control group (P < 0.05). Furthermore, subsequent activator and/or inhibitor experiments validated that heat stress modulated HSP70 and AMPK signalling pathways to enhance lipogenesis and inhibit lipolysis in porcine subcutaneous preadipocytes. Importantly, this study reveals, for the first time, that EGCG mitigates heat-stress-induced fat deposition by targeting HSP70 through the activation of AMPK-SIRT1-PGC-1α in porcine subcutaneous preadipocytes. These findings elucidate the molecular mechanisms contributing to heat stress-induced obesity and provide a foundation for the potential clinical utilisation of EGCG as a preventive measure against both heat stress and obesity. Show less

Nannochloropsis species should be given priority when it comes to microalgae that should be added to feed since they are suitable for intense culture and have a high concentration of PUFAs (especially EPA), antioxidants, and certain vitamins. This study investigated the possible immune and antioxidant impacts of Nannochloropsis supplementation on Barki ewes during transition period and their newly born lambs. Three weeks prior to the expected time of lambing, the researched ewes were divided into two equal groups of thirty ewes each. The second group, on the other hand, was fed the same base diet as the first group plus 10 g of commercially available Nannochloropsis powder per kg of concentrate, given daily to each ewe's concentrate. Findings revealed that supplementation of ewes with Nannochloropsis significantly up-regulated the expression pattern of immune (NFKB, RANTES, HMGB1, TNF-α, IRF4, TLR7, CLA-DRB3.2, IL1B, IL6, CXCL8, S-LZ, and Cathelicidin), and antioxidant (SOD1, CAT, GPX1, GST, ATOX1, Nrf2 and AhpC/TSA) markers in ewes post-lambing and their newly born lambs. Additionally, mRNA levels of lipogenic (ACACA, FASN SCD, LPL, and BTN1A) markers were significantly up-regulated in lambs from supplemented ewes than control ones. There was a significant increase in the WBCs, Hb, RBc count, serum level of glucose, total protein, triacylglycerol and total cholesterol, GPx, catalase, IL1α and IL6 with significantly decreased serum level of TNF-α and MDA in supplemented ewes after lambing as compared with control ones. There was also a significant increase in WBCs, Hb, RBc count, birth weight and body temperature with significantly decreased in the serum levels of TNF-α and stillbirth of newly born lambs from supplemented ewes as compared to other lambs from control ones. Show less

The number of patients with lifestyle-related diseases such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has continued to increase worldwide. Therefore, development of innovative therapeutic methods targeting lifestyle-related diseases is required. Gene therapy has attracted considerable attention as an advanced medical treatment. Safe and high-performance vectors are essential for the practical application of gene therapy. Replication-incompetent adenovirus (Ad) vectors are widely used in clinical gene therapy and basic research. Here, we developed a novel Ad vector, named Ad-E4-122aT, exhibiting higher and longer-term transgene expression and lower hepatotoxicity than conventional Ad vectors. We also elucidated the mechanisms underlying Ad vector-induced hepatotoxicity during the early phase using Ad-E4-122aT. Next, we examined the therapeutic effects of the genes of interest, namely zinc finger AN1-type domain 3 (ZFAND3), lipoprotein lipase (LPL), and lysophospholipid acyltransferase 10 (LPLAT10), on lifestyle-related diseases using Ad-E4-122aT. We showed that the overexpression of ZFAND3 in the liver improved glucose tolerance and insulin resistance. Liver-specific LPL overexpression suppressed hepatic lipid accumulation and improved glucose metabolism. LPLAT10 overexpression in the liver suppressed postprandial hyperglycemia by increasing glucose-stimulated insulin secretion. Furthermore, we also focused on foods to advance research on the pathophysiology and treatment of lifestyle-related diseases. Cranberry and calamondin, which are promising functional foods, attenuated the progression of MASLD/NAFLD. Our findings will aid the development of new therapeutic methods, including gene therapy, for lifestyle-related diseases such as T2DM and MASLD/NAFLD. Show less

Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD. Show less

This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (P < 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (P = 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (P = 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability. Show less

Our case report is of an elderly male with a history of IgM κ lymphoplasmacytic lymphoma (LPL) presenting with generalized neuropathy and weakness. Due to his LPL history and worsening renal function, he underwent a renal biopsy revealing the presence of μ heavy and λ light chains, revealing a diagnosis of amyloidosis with unbound heavy & light chains (AHL), a rare type of amyloidosis. His bone marrow biopsy demonstrated κ light chain restriction by flow cytometry and amyloid deposition. The patient's serum had elevated free κ and λ light chains with a free light chain (FLC) ratio of 3.17. Serum immunofixation was positive for IgM κ and λ light chain clones. He completed six cycles of cyclophosphamide, bortezomib, dexamethasone, and rituximab (CyBorD+R), normalizing the FLC ratio. Still, he continued to present with persistently elevated M protein, IgM κ, and λ light chains on immunofixation. Thereafter, daratumumab, a human monoclonal antibody directed against CD38 expressed on myeloma cells was initiated, which led to a negative immunofixation study after two cycles accompanied by a reduction in protein excretion in the urine. The patient achieved a complete hematological response with daratumumab. To date, our case is the only reported μ heavy and λ light chain amyloidosis patient with bi-clonal (IgM κ and λ) gammopathy to be successfully treated with daratumumab. Show less

In the present work, the 3T3-L preadipocytes were utilized to explore the impact of Obtained results showed the ability of RCE to reduce lipid overloads in hypertrophic adipocytes associated with the down-regulation of mRNA expressions of adipogenic transcription factors such as Show less

Familial chylomicronemia syndrome (FCS) is one of the rare causes of hypertriglyceridemia. Plasmapheresis is recommended in patients with triglyceride levels greater than 2000 mg/dL. However, plasmapheresis is difficult to perform in most centers due to technical inadequacies in the neonatal period. There are some reports in the literature on the efficacy of exchange transfusion. The index case involves a 20-day-old male patient who was admitted to the emergency department for restlessness and poor feeding. He was born at term with a birth weight of 4000 g. He was exclusively breastfed. The patient was taken to the neonatal intensive care unit due to his plasma being in the form of excessive lipemia. The first measurable triglyceride level was 5100 mg/dL (57.6 mmol/L). Breast milk was restricted, and intravenous hydration was started. However, his triglyceride level did not decrease despite this treatment. Other laboratory values could not be read due to excessive lipemic serum. On the third day of hospitalization, an exchange transfusion was decided upon in this case due to the development of respiratory distress (oxygen support, tachypnea). After exchange transfusion, the patient's triglyceride level reduced dramatically to 592 mg/dL (6.6 mmol/L), and his respiratory symptoms resolved. The aim of this case report is to demonstrate that exchange transfusion therapy is a safe and effective treatment modality in the neonatal period for the acute management of FCS. Furthermore, dietary therapy restricted to long-chain fatty acids combined with medium-chain fatty acid supplementation is highly effective in the chronic management of these patients. Show less

Inclusion of lysophospholipids (LPL) has been proposed to increase growth performance in broilers and pigs, acting as emulsifiers through mixed micelle formation. The aim of this study was to investigate the effect of feeding LPL in weanling pig diets on growth performance and intestinal morphology. Eight hundred pigs (weight 6.96 kg ± SD 1.58 kg) were assigned to one of two dietary treatments, i.e., a basal diet (CON) or a basal diet + 0.05% lysophospholipids (LPL). The experimental period lasted for 42 days, and on days 40 and 41, 32 pigs in total were euthanized for intestinal tissue samples. From days 14 to 21, feed intake and average daily gain increased, as well as FCR, from days 28 to 42, in the LPL group compared with the CON group. In the overall period, no differences in growth performance were present between the groups. However, females displayed increased ADG from days 21 to 28 compared with castrates. The villous height tended ( Show less

High-fat diets (HFDs) enhance fish growth by optimizing nutrient utilization (i.e., protein-sparing effect); however, their potential negative effects have also encouraged the search for feed additives. This work has investigated the effects of an extract rich in a polyphenolic antioxidant, hydroxytyrosol (HT), supplemented (0.52 g HT/kg feed) in a HFD (24% lipid) in gilthead sea bream ( Show less