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Cancer Reports (Hoboken, N.J.) Jun 2024Liver metastasis of CRC is still the main cause of poor prognosis in patients with CRC. Previous studies have suggested that serpin family C member 1(SERPINC1) is...
BACKGROUND
Liver metastasis of CRC is still the main cause of poor prognosis in patients with CRC. Previous studies have suggested that serpin family C member 1(SERPINC1) is involved in the development of a variety of tumours, but its effect on colorectal cancer progression has been poorly elucidated.
METHODS
Based on the GEO database, this study identifies the core gene SERPINC1 associated with liver metastasis in CRC. We used transcriptomic data and immunohistochemical staining to explore the expression of SERPINC1 in normal, cancer, and liver metastases tissue from CRC patients. Clinical data obtained from our hospital were used to explore the impact of SERPINC1 on the prognosis of colon cancer patients. Mechanistically, the biological functions exerted by SERPINC1 in CRC were predicted by bioinformatics, and the results were validated by the results of the experiments in vitro. Cell lines with knockdown of SERPINC1 were performed a series assay such as trans well, CCK-8 and colony formation assay to explore the relationship between SERPINC1 and proliferation and metastasis of CRC cells. Finally, the effect of SERPINC1 on the sensitivity of colon cancer patients to immune checkpoint therapy was evaluated.
RESULTS
In CRC liver metastatic tissues, we found significantly high expression of SERPINC1. Briefly, 212 CRC cohorts showed that SERPINC1 was significantly associated with TNM stage and plasma CA19-9 and CEA in CRC patients. Univariate and multivariate Cox demonstrated that SERPINC1 was significantly associated with 5-year survival after radical surgery for colorectal cancer (p < 0.001). Bioinformatics predicted that SERPINC1 affects metastasis of colon cancer through epithelial-mesenchymal transition (EMT). Colony formation assay and CCK-8 assay showed that SERPINC1 promotes malignant proliferation of CRC cells, trans well assay showed that SERPINC1 promotes distant migratory behaviour of CRC cells and protein blotting assay showed that SERPINC1 may promote migration by promoting the TGF-β1-mediated EMT of CRC cells. In addition, several immunotherapy cohorts also reflected that the expression of SERPINC1 reduced the sensitivity of CRC patients to immune checkpoint therapy.
CONCLUSION
Our study identified SERPINC1 as a novel liver metastasis-associated gene in CRC. Targeting SERPINC1 may be a novel therapeutic strategy for patients with liver metastases from CRC.
Topics: Humans; Epithelial-Mesenchymal Transition; Prognosis; Liver Neoplasms; Male; Disease Progression; Colonic Neoplasms; Female; Biomarkers, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Middle Aged; Cell Line, Tumor; Cell Movement; Immune Checkpoint Inhibitors; Colorectal Neoplasms
PubMed: 38923313
DOI: 10.1002/cnr2.2079 -
Toxins May 2024As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to...
As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.
Topics: Humans; Muscle Spasticity; Male; Female; Retrospective Studies; Middle Aged; Urinary Bladder, Overactive; Adult; Spinal Cord Injuries; Multiple Sclerosis; Neuromuscular Agents; Botulinum Toxins, Type A; Urinary Bladder, Neurogenic; Aged; Injections, Intramuscular; Treatment Outcome
PubMed: 38922146
DOI: 10.3390/toxins16060252 -
Journal of Fungi (Basel, Switzerland) Jun 2024Entomopathogenic fungi have been considered potential biological control agents against the fall armyworm (J. E. Smith), the world's most important pest of maize. In...
Entomopathogenic fungi have been considered potential biological control agents against the fall armyworm (J. E. Smith), the world's most important pest of maize. In this study, we evaluated the natural infection, molecular characteristics, and biological activity of (Farlow) isolated from larvae of this insect, collected from maize crops in five Mexican locations. Natural infection ranged from 23% to 90% across all locations analyzed. Twenty-four isolates were evaluated on second instars at a concentration of 1.0 × 10 conidia/mL, causing 70% to 98.7% mortality and 60.5% to 98.7% sporulation. Isolates T9-21, Z30-21, PP48-21, and L8-22 were selected to determine their phylogenetic relationships by gene analysis and to compare median lethal concentration (CL), median lethal time (LT), and larval survival. These isolates were grouped into three clades. The T9-21, PP48-21, and J10-22 isolates were closely related (clade A), but phylogenetically distant from Z30-21 (clade B) and L8-22 (clade C) isolates. These genetic differences were not always reflected in their pathogenicity characteristics since no differences were observed among the LC values. Furthermore, isolates T9-21, J10-22, and L8-22 were the fastest to kill larvae, causing lower survival rates. We conclude that native isolates represent an important alternative for the biocontrol of .
PubMed: 38921402
DOI: 10.3390/jof10060416 -
Biomimetics (Basel, Switzerland) Jun 2024This study aims to support designers in developing transformative solutions in the engineering discipline using the Design-by-Analogy ideation method. Design-by-Analogy...
This study aims to support designers in developing transformative solutions in the engineering discipline using the Design-by-Analogy ideation method. Design-by-Analogy involves drawing inspiration from the source domain and applying it to the target domain. Based on the conceptual distance between the two domains, analogies are classified as biological-(natural), cross-(distant-engineering), and within-(near-engineering) domain analogies. Real-world scenarios involve designers selecting analogies after seeking them across multiple domains. These selected analogies significantly influence the produced designs. However, the selection criteria of the analogy domain are unexplored in design research. We address this gap by investigating: (a) the influence of analogy domains on their selection frequency; and (b) the relationship between the frequency of selecting analogies from specific domains and the novelty of designs. The experiment involved twenty-six teams of novice product designers, who solved design problems aided by one analogical source from each domain. The results showed that biological analogies were frequently selected. While biological-domain analogies significantly increased the novelty of designs compared to the within-domain ones; no significant difference was found between the biological- and cross-domain analogies, suggesting that middle-domain analogies can be as effective as far-domain ones. The findings can support technological innovation by aiding the development of analogy search databases.
PubMed: 38921224
DOI: 10.3390/biomimetics9060344 -
MBio Jun 2024The cytotoxic necrotizing factor (CNF) family of AB-type bacterial protein toxins catalyze two types of modification on their Rho GTPase substrates: deamidation and...
The cytotoxic necrotizing factor (CNF) family of AB-type bacterial protein toxins catalyze two types of modification on their Rho GTPase substrates: deamidation and transglutamination. It has been established that CNF1 and its close homolog proteins catalyze primarily deamidation and dermonecrotic toxin (DNT) catalyzes primarily transglutamination. The rapidly expanding microbial genome sequencing data have revealed that there are at least 13 full-length variants of CNF1 homologs. CNFx from strain GN02091 is the most distant from all other members of the CNF family with 50%-55% sequence identity at the protein level and 0.45-0.52 nucleotide substitutions per site at the DNA level. CNFx modifies RhoA, Rac1, and Cdc42, and like CNF1, activates downstream SRE-dependent mitogenic signaling pathways in human HEK293T cells, but at a 1,000-fold higher EC value. Unlike other previously characterized CNF toxins, CNFx modifies Rho proteins primarily through transglutamination, as evidenced by gel-shift assay and confirmed by MALDI mass spectral analysis, when coexpressed with Rho-protein substrates in BL21 cells or through direct treatment of HEK293T cells. A comparison of CNF1 and CNFx sequences identified two critical active-site residues corresponding to positions 832 and 862 in CNF1. Reciprocal site-specific mutations at these residues in each toxin revealed hierarchical rules that define the preference for deamidase versus a transglutaminase activity in CNFs. An additional unique Cys residue at the C-terminus of CNFx was also discovered to be critical for retarding cargo delivery.IMPORTANCECytotoxic necrotizing factor (CNF) toxins not only play important virulence roles in pathogenic and other bacterial pathogens, but CNF-like genes have also been found in an expanding number of genomes from clinical isolates. Harnessing the power of evolutionary relationships among the CNF toxins enabled the deciphering of the hierarchical active-site determinants that define whether they modify their Rho GTPase substrates through deamidation or transglutamination. With our finding that a distant CNF variant (CNFx) unlike other known CNFs predominantly transglutaminates its Rho GTPase substrates, the paradigm of "CNFs deamidate and DNTs transglutaminate" could finally be attributed to two critical amino acid residues within the active site other than the previously identified catalytic Cys-His dyad residues. The significance of our approach and research findings is that they can be applied to deciphering enzyme reaction determinants and substrate specificities for other bacterial proteins in the development of precision therapeutic strategies.
PubMed: 38920360
DOI: 10.1128/mbio.01221-24 -
Genome Biology and Evolution Jun 2024The European sprat is a small plankton-feeding clupeid present in the northeastern Atlantic Ocean, the Mediterranean Sea as well as in the brackish Baltic Sea and Black...
The European sprat is a small plankton-feeding clupeid present in the northeastern Atlantic Ocean, the Mediterranean Sea as well as in the brackish Baltic Sea and Black Sea. This species is the target of a major fishery and therefore an accurate characterization of its genetic population structure is crucial to delineate proper stock assessments that aid ensuring the fishery's sustainability. Here we present (i) a draft genome assembly, (ii) pooled whole genome sequencing of 19 population samples covering most of the species' distribution range, and (iii) the design and test of a SNP-chip resource and use this to validate the population structure inferred from pooled sequencing. These approaches revealed, using the populations sampled here, three major groups of European sprat: Oceanic, Coastal, and Brackish with limited differentiation within groups even over wide geographical stretches. Genetic structure is largely driven by six large putative inversions that differentiate Oceanic and Brackish sprats, while Coastal populations display intermediate frequencies of haplotypes at each locus. Interestingly, populations from the Baltic and the Black Seas share similar frequencies of haplotypes at these putative inversions despite their distant geographic location. The closely related clupeids European sprat and Atlantic herring both show genetic adaptation to the brackish Baltic Sea, providing an opportunity to explore the extent of genetic parallelism. This analysis revealed limited parallelism because out of 125 independent loci detected in the Atlantic herring, three showed sharp signals of selection that overlapped between the two species and contained single genes such as PRLRA, which encodes the receptor for prolactin, a freshwater-adapting hormone in euryhaline species, and THRB, a receptor for thyroid hormones, important both for metabolic regulation and the development of red cone photoreceptors.
PubMed: 38918882
DOI: 10.1093/gbe/evae133 -
World Journal of Surgical Oncology Jun 2024The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS.
METHODS
We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460).
RESULTS
From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53-1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50-0.99]; P = 0.04).
CONCLUSIONS
This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.
Topics: Female; Humans; Carcinoma, Ovarian Epithelial; Fertility Preservation; Neoplasm Recurrence, Local; Neoplasm Staging; Organ Sparing Treatments; Ovarian Neoplasms; Prognosis; Survival Rate
PubMed: 38918840
DOI: 10.1186/s12957-024-03440-3 -
Asian Pacific Journal of Cancer... Jun 2024Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in...
BACKGROUND
Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients.
MATERIAL & METHODS
We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival.
RESULTS
Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival.
CONCLUSIONS
Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.
Topics: Humans; Male; Colorectal Neoplasms; Female; Receptor, ErbB-2; Middle Aged; Egypt; Prognosis; Survival Rate; Biomarkers, Tumor; Gene Amplification; Aged; Adult; Follow-Up Studies; In Situ Hybridization, Fluorescence; Lymphatic Metastasis; Neoplasm Staging; Immunohistochemistry
PubMed: 38918664
DOI: 10.31557/APJCP.2024.25.6.2023 -
Scientific Reports Jun 2024People procrastinate, but why? One long-standing hypothesis is that temporal discounting drives procrastination: in a task with a distant future reward, the discounted...
People procrastinate, but why? One long-standing hypothesis is that temporal discounting drives procrastination: in a task with a distant future reward, the discounted future reward fails to provide sufficient motivation to initiate work early. However, empirical evidence for this hypothesis has been lacking. Here, we used a long-term real-world task and a novel measure of procrastination to examine the association between temporal discounting and real-world procrastination. To measure procrastination, we critically measured the entire time course of the work progress instead of a single endpoint, such as task completion day. This approach allowed us to compute a fine-grained metric of procrastination. We found a positive correlation between individuals' degree of future reward discounting and their level of procrastination, suggesting that temporal discounting is a cognitive mechanism underlying procrastination. We found no evidence of a correlation when we, instead, measured procrastination by task completion day or by survey. This association between temporal discounting and procrastination offers empirical support for targeted interventions that could mitigate procrastination, such as modifying incentive systems to reduce the delay to a reward and lowering discount rates.
Topics: Humans; Procrastination; Delay Discounting; Male; Female; Reward; Adult; Motivation; Young Adult
PubMed: 38918442
DOI: 10.1038/s41598-024-65110-4 -
Microbiology Resource Announcements Jun 2024Complete genome data for the globally distributed Aedes flavivirus (AEFV) is scarce. We analyzed a new Italian AEFV strain isolated from . The results demonstrated...
Complete genome data for the globally distributed Aedes flavivirus (AEFV) is scarce. We analyzed a new Italian AEFV strain isolated from . The results demonstrated genetic diversity among Italian AEFVs. The high similarity between AEFV genomes across geographically distant regions suggests long distance spreading via invasive host mosquito species.
PubMed: 38917449
DOI: 10.1128/mra.00146-24