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Foods (Basel, Switzerland) May 2024A fundamental regulatory framework to elucidate the role of electrical stimulation (ES) in reducing long production cycles, enhancing protein utilization, and boosting...
Electrical Stimulation Induces Activation of Mitochondrial Apoptotic Pathway and Down-Regulates Heat Shock Proteins in Pork: An Innovative Strategy for Enhancing the Ripening Process and Quality of Dry-Cured Loin Ham.
A fundamental regulatory framework to elucidate the role of electrical stimulation (ES) in reducing long production cycles, enhancing protein utilization, and boosting product quality of dry-cured ham is essential. However, how mitochondria and enzymes in meat fibers are altered by ES during post-processing, curing, and fermentation procedures remains elusive. This study sought to explore the impact of ES on the regulation of heat shock proteins (HSP27, HSP70), apoptotic pathways, and subsequent influences on dry-cured pork loin quality. The gathered data validated the hypothesis that ES notably escalates mitochondrial oxidative stress and accelerates mitochondrial degradation along the ripening process. The proapoptotic response in ES-treated samples was increased by 120.7%, with a cellular apoptosis rate 5-fold higher than that in control samples. This mitochondrial degradation is marked by increased ratios of Bax/Bcl-2 protein along the time course, indicating that apoptosis could contribute to the dry-cured ham processing. ES was shown to further down-regulate HSP27 and HSP70, establishing a direct correlation with the activation of mitochondrial apoptosis pathways, accompanied by dry-cured ham quality improvements. The findings show that ES plays a crucial role in facilitating the ripening of dry-cured ham by inducing mitochondrial apoptosis to reduce HSP expression. This knowledge not only explains the fundamental mechanisms behind myofibril degradation in dry-cured ham production but also offers a promising approach to enhance quality and consistency.
PubMed: 38890945
DOI: 10.3390/foods13111717 -
Foods (Basel, Switzerland) May 2024Amylose content (AC) stands as a pivotal determinant of rice grain quality, primarily governed by the gene (). The allelic variation within this gene, particularly the...
Amylose content (AC) stands as a pivotal determinant of rice grain quality, primarily governed by the gene (). The allelic variation within this gene, particularly the presence of the allele derived from the ancestral allele, significantly influences AC and is prevalent among soft rice varieties in southern China. Although both alleles are associated with lower AC, there remains a paucity of detailed understanding regarding the interplay between specific functional single nucleotide polymorphisms (SNPs) within these alleles and the overarching rice grain quality. To investigate this, we engineered three distinct transgenic rice lines, each harboring the , , or alleles in the background of the glutinous rice cultivar Nip(). This suite of transgenic rice lines showcased varying degrees of grain transparency inversely correlated to AC, which in turn influenced other physicochemical properties of the rice grains, such as taste value of cooked rice, gel consistency, and starch pasting properties. Additionally, analyses of gene expression and enzyme activity revealed that the functional SNPs, Ex4-53G to A and Ex5-53T to C, lead to a decline in the activity of granule-bound starch synthase I (GBSSI) without altering expression levels.
PubMed: 38890853
DOI: 10.3390/foods13111624 -
Neuropsychopharmacology Reports Jun 2024Anticholinergic toxicity is a common occurrence in the emergency room, making it crucial for emergency clinicians to have a good understanding of this toxidrome. The...
Anticholinergic toxicity is a common occurrence in the emergency room, making it crucial for emergency clinicians to have a good understanding of this toxidrome. The neuropsychiatric effects of anticholinergic agents and anabolic steroids (ASs) can manifest as symptoms like anxiety, agitation, dysarthria, confusion, seizures, visual hallucinations, bizarre behavior, delirium, psychosis, and coma. When dealing with a conscious patient who has ingested an anticholinergic substance, a detailed history of ingestion can aid clinicians in making an accurate diagnosis. However, the lack of information about the substances consumed can complicate diagnosis. In cases where the exposure is unknown, clinicians should consider anticholinergic poisoning in patients showing signs of altered mental status and physical examination findings consistent with anticholinergic toxicity. We report four cases presenting a range of symptoms, including neuropsychiatric manifestations, following the ingestion of the same bodybuilding powders with anticholinergic properties. All four patients consumed yellow and white powders at the same time and in the same place. Laboratory analysis revealed that yellow powder and white powder contained ASs and cyproheptadine, respectively.
PubMed: 38889254
DOI: 10.1002/npr2.12460 -
Clinical Cardiology Jun 2024Atherosclerotic cardiovascular disease (ASCVD) is a group of clinical diseases based on pathology of atherosclerosis that is the leading cause of mortality worldwide....
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is a group of clinical diseases based on pathology of atherosclerosis that is the leading cause of mortality worldwide. There is a bidirectional interaction between ASCVD and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alterations in circulating miRNAs levels are involved in the development of ASCVD in patients infected with SARS-CoV-2, however, the correlation between ASCVD co-infection with SARS-CoV-2 and alterations of cardiac-specific miRNAs is not well understood.
HYPOTHESIS
The circulating miR-146a and miR-27a are involved in bidirectional interactions between ASCVD and SARS-CoV-2 infections.
METHODS
Circulating miR-146a and miR-27a levels were measured in serum and PBMCs deriving from ASCVD patients and controls after SARS-CoV-2 infection by qRT-PCR analysis. The levels of neutralizing antibodies-resistant SARS-CoV-2 in human serum was determined by competitive magnetic particle chemiluminescence method. Interleukin (IL)-6 levels were detected by automatic biochemical analyzer using electrochemiluminescence.
RESULTS
Significant downregulation of circulating miR-146a and upregulation of miR-27a in ASCVD patients after infection with SARS-CoV-2 compared with controls were observed, among which the alterations were more evident in ASCVD patients comorbid with hyperlipidemia and diabetes mellitus. Consistently, correlation analysis revealed that serum miR-146a and miR-27a levels were associated with the levels of lipids and glucose, inflammatory response, and immune function in ASCVD patients. Remarkably, SARS-CoV-2 S protein RBD stimulation of PBMCs derived from both ASCVD and controls significantly downregulated miR-146a, upregulated miR-27a expression levels, and promoted IL-6 release in vitro.
CONCLUSIONS
The circulating miR-146a and miR-27a are involved in metabolism, inflammation, and immune levels in patients with ASCVD after SARS-CoV-2 infection, laying the foundation for the development of strategies to prevent the risk of SARS-CoV-2 infection in ASCVD patients.
Topics: Humans; COVID-19; MicroRNAs; Male; Female; Middle Aged; Atherosclerosis; SARS-CoV-2; Aged; Biomarkers; Circulating MicroRNA
PubMed: 38884329
DOI: 10.1002/clc.24274 -
Integrative Organismal Biology (Oxford,... 2024Meiofauna (benthic invertebrates < 1 mm in size) facilitate sediment biogeochemical cycling, alter sediment microbial community structure, and serve as an important...
Meiofauna (benthic invertebrates < 1 mm in size) facilitate sediment biogeochemical cycling, alter sediment microbial community structure, and serve as an important trophic link between benthic micro- and macrofauna, yet the behaviors that mechanistically link individuals to their ecological effects are largely unknown. Meiofauna are small and sediments are opaque, making observing the activities of these animals challenging. We developed the Meioflume, a small, acrylic flow tunnel filled with grains of cryolite, a transparent sand analog, to simulate the conditions experienced by meiofauna in an observable lab environment. The Meioflume has a working area (28.57 mm × 10.16 mm × 1 mm) that is small enough to quickly locate fauna and clearly observe behavior but large enough that animals are not tightly confined. When connected to a syringe press, the Meioflume can produce low velocity flows consistently and evenly across the width of its working area while retaining the contents. To demonstrate its functionality in observing the behavior of meiofauna, we placed individual meiofaunal animals (a protodrilid annelid, a harpacticoid copepod, and a platyhelminth flatworm) in Meioflumes and filmed their behavioral response to a sudden initiation of porewater flow. All animals were clearly visible within the flume and could be observed responding to the onset of flow. The design and construction of the Meioflume make it an accessible, affordable tool for researchers. This experimental system could be modified to address many questions in meiofaunal ecology, such as studying behavior in response to chemical cues, allowing us to observe meiofaunal behaviors to better understand their ecological effects.
PubMed: 38883566
DOI: 10.1093/iob/obae016 -
American Journal of Translational... 2024The purpose of this study is to decipher the role of Cullin family genes in colorectal cancer (CRC), drawing insights from comprehensive analyses encompassing multiple...
OBJECTIVES
The purpose of this study is to decipher the role of Cullin family genes in colorectal cancer (CRC), drawing insights from comprehensive analyses encompassing multiple databases and experimental validations.
METHODS
UALCAN, GEPIA2, Human Protein Atlas (HPA), KM plotter, cBioPortal, TISIDB, DAVID, colon cancer cell lines culturing, gene knockdown, CCK8 assay, colony formation, and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) assays.
RESULTS
Initial scrutiny of The Cancer Genome Atlas (TCGA) CRC datasets through the UALCAN and GEPIA databases unveiled significant alterations in Cullin family gene expressions. Elevations in CUL1, CUL2, CUL4A, CUL4B, CUL5, CUL7, and CUL9 were observed in CRC tissues compared to normal counterparts, while CUL3 demonstrated down-regulation consistently across datasets. Further exploration revealed notable correlations between Cullin gene expressions and various clinical parameters of CRC patients, substantiating the potential diagnostic and prognostic utility of these genes. Protein expression analyses conducted via the HPA corroborated the transcriptomic findings, indicating high levels of Cullin proteins in CRC tissues. Prognostic assessments identified CUL7 and CUL9 as significant predictors of poor survival outcomes in CRC patients, emphasizing their clinical relevance. Genetic alterations within the Cullin family genes were elucidated through the cBioPortal database, shedding light on the mutation landscape and prevalence of missense mutations in CRC. Immune subtype and tumor immune microenvironment analyses underscored the intricate interplay between Cullin family genes and immune processes in CRC. Experimental validation in CRC cell lines demonstrated the functional significance of CUL7 and CUL9 in promoting CRC growth, further solidifying their roles as potential therapeutic targets.
CONCLUSION
Overall, these multifaceted analyses elucidated the intricate involvement of Cullin family genes in CRC pathogenesis and provided valuable insights for future diagnostic and therapeutic endeavors in CRC management.
PubMed: 38883340
DOI: 10.62347/CHIB8915 -
Frontiers in Plant Science 2024Isotopic signatures offer new methods, approaches, and perspectives for exploring the ecological adaptability and functions of plants. We examined pattern differences in...
Isotopic signatures offer new methods, approaches, and perspectives for exploring the ecological adaptability and functions of plants. We examined pattern differences in the isotopic signatures ( C, N, S) of across varying plant life-death status along geographic clines. We extracted 539 sets of isotopic data from 57 publications covering 267 sites across a latitude range of over 23.8° along coastal wetlands. Responses of isotopic signatures to climate drivers (MAT and MAP) and the internal relationships between isotopic signatures were also detected. Results showed that the C, N, and S of were -13.52 ± 0.83‰, 6.16 ± 0.14‰, and 4.01 ± 6.96‰, with a range of -17.44‰ to -11.00‰, -2.40‰ to 15.30‰, and -9.60‰ to 15.80‰, respectively. The latitudinal patterns of C, N, and S in were shaped as a convex curve, a concave curve, and an increasing straight line, respectively. A decreasing straight line for C within the ranges of MAT was identified under plant life status. Plant life-death status shaped two nearly parallel decreasing straight lines for S in response to MAT, resulting in a concave curve of S for live in response to MAP. The N of significantly decreased with increasing C of , except for plant death status. The C, N, and S of . are consistent with plant height, stem diameter, leaf traits, etc, showing general latitudinal patterns closely related to MAT. Plant life-death status altered the N (live: 6.55 ± 2.23‰; dead: -2.76 ± 2.72‰), latitudinal patterns of . and their responses to MAT, demonstrating strong ecological plasticity and adaptability across the geographic clines. The findings help in understanding the responses of latitudinal patterns of the C, N, and S isotope signatures of in response plant life-death status, and provide evidence of robust ecological plasticity and adaptability across geographic clines.
PubMed: 38882576
DOI: 10.3389/fpls.2024.1384914 -
Clinical Lung Cancer May 2024In clinical trials, frontline pembrolizumab for advanced NSCLC has demonstrated durable, clinically meaningful, long-term survival benefits over chemotherapy. Our...
BACKGROUND
In clinical trials, frontline pembrolizumab for advanced NSCLC has demonstrated durable, clinically meaningful, long-term survival benefits over chemotherapy. Our objective was to evaluate 5-year survival rates outside the idealized setting of clinical trials for advanced/metastatic NSCLC treated with frontline pembrolizumab monotherapy.
METHODS
Using a nationwide, electronic health record-derived, deidentified database in the United States, we studied adult patients with advanced/metastatic NSCLC (unresectable stage IIIB/IIIC, or stage IV), with PD-L1 expression ≥ 50%, no documented EGFR, ALK, or ROS1 genomic alteration, and ECOG performance status of 0-1 initiating frontline pembrolizumab monotherapy from November 1, 2016, through March 31, 2020, excluding those in clinical trials. Kaplan-Meier was used to determine overall survival (OS). Data cutoff was May 31, 2023.
RESULTS
A total of 804 patients were eligible for the study, including 404 women (50%); median age was 72 years (range, 38-85 years), with 310 patients (39%) ≥ 75 years old. Median follow-up time from pembrolizumab initiation to data cutoff was 60.5 months (range, 38.0-78.7). At data cutoff, 549 patients (68%) had died. Median OS was 19.2 months (95% CI, 16.6-21.4), and survival rate at 5 years was 25.1% (95% CI, 21.7-28.7). Overall, 266 patients (33%) received 1 or more subsequent regimens, most commonly an anti-PD-(L)1 agent (as monotherapy or combination therapy) or platinum-based chemotherapy.
CONCLUSIONS
With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness, with survival outcomes consistent with those of pivotal clinical trials, for treating patients with advanced NSCLC with PD-L1 expression of ≥ 50% and no EGFR, ALK, or ROS1 genomic alteration.
PubMed: 38880664
DOI: 10.1016/j.cllc.2024.05.002 -
Virus Research Jun 2024Due to the spread of multidrug resistance there is a renewed interest in using bacteriophages (briefly: phages) for controlling bacterial pathogens. The objective of...
Due to the spread of multidrug resistance there is a renewed interest in using bacteriophages (briefly: phages) for controlling bacterial pathogens. The objective of this study was the characterization of a newly isolated phage (i.e. phage LAPAZ, vB_KpnD-LAPAZ), its antimicrobial activity against multidrug resistant Klebsiella pneumoniae and potential synergistic interactions with antibiotics. LAPAZ belongs to the family Drexlerviridae (genus: Webervirus) and lysed 30 % of tested strains, whereby four distinct capsular types can be infected. The genome consists of 51,689 bp and encodes 84 ORFs. The latent period is 30 min with an average burst size of 27 PFU/cell. Long-term storage experiments show that LAPAZ is significantly more stable in wastewater compared to laboratory media. A phage titre of 90 % persists up to 30 min at 50 ˚C and entire phage loss was seen only at temperatures > 66 ˚C. Besides stability against UV-C, antibacterial activity in liquid culture medium was consistent at pH values ranging from 4 to 10. Unlike exposure to phage or antibiotic alone, synergistic interactions and a complete bacterial eradication was achieved when combining LAPAZ with meropenem. In addition, synergism with the co-presence of ciprofloxacin was observed and phage resistance emergence could be delayed. Without co-addition of the antibiotic, phage resistant mutants readily emerged and showed a mixed pattern of drug sensitivity alterations. Around 88 % became less sensitive towards ceftazidime, meropenem and gentamicin. Conversely, around 44 % showed decreased resistance levels against ciprofloxacin. Whole genome analysis of a phage-resistant mutant with a 16-fold increased sensitivity towards ciprofloxacin revealed one de novo frameshift mutation leading to a gene fusion affecting two transport proteins belonging to the major facilitator-superfamily (MFS). Apparently, this mutation compromises ciprofloxacin efflux efficiency and further studies are warranted to understand how the non-mutated protein might be involved in phage-host adsorption.
PubMed: 38880333
DOI: 10.1016/j.virusres.2024.199417 -
Cell Communication and Signaling : CCS Jun 2024Sex-specific gonadal differentiation is directed by complex signalling promoting development in either male or female direction, while simultaneously inhibiting the...
Sex-specific gonadal differentiation is directed by complex signalling promoting development in either male or female direction, while simultaneously inhibiting the opposite pathway. In mice, the WNT/β-catenin pathway promotes ovarian development and the importance of actively inhibiting this pathway to ensure normal testis development has been recognised. However, the implications of alterations in the tightly regulated WNT/β-catenin signalling during human fetal gonad development has not yet been examined in detail. Thus, the aim of this study was to examine the consequences of dysregulating the WNT/β-catenin signalling pathway in the supporting cell lineage during sex-specific human fetal gonad development using an established and extensively validated ex vivo culture model. Inhibition of WNT/β-catenin signalling in human fetal ovary cultures resulted in only minor effects, including reduced secretion of RSPO1 and reduced cell proliferation although this was not consistently found in all treatment groups. In contrast, promotion of WNT/β-catenin signalling in testes severely affected development and function. This included disrupted seminiferous cord structures, reduced cell proliferation, reduced expression of SOX9/AMH, reduced secretion of Inhibin B and AMH as well as loss of the germ cell population. Additionally, Leydig cell function was markedly impaired with reduced secretion of testosterone, androstenedione and INSL3. Together, this study suggests that dysregulated WNT/β-catenin signalling during human fetal gonad development severely impairs testicular development and function. Importantly, our study highlights the notion that sufficient inhibition of the opposite pathway during sex-specific gonadal differentiation is essential to ensure normal development and function also applies to human fetal gonads.
Topics: Humans; Male; Wnt Signaling Pathway; Testis; Female; Sex Differentiation; Fetus; Cell Differentiation; Cell Proliferation; beta Catenin; Leydig Cells; Ovary
PubMed: 38879537
DOI: 10.1186/s12964-024-01704-9