BACKGROUND AND AIM: The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity. METHODS: There were 173 patients with AP, all of whom developed symptoms within 72 h; 102 individuals had onset symptoms within 48 h. The biomarkers were measured upon admission before determining the severity of AP. RESULTS: The levels of TAT, plasmin-α2-plasmin inhibitor complex, TM, and t-PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72 h of onset, TAT, TM, and t-PAIC predicted the occurrence of SAP. For the patients within 48 h of onset, TAT and t-PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C-reactive protein (P < 0.05). Notably, t-PAIC had a larger AUC than TAT, BISAP, and C-reactive protein. CONCLUSION: In the initial 48 h, plasma TAT and t-PAIC levels may predict the development of SAP. Within 72 h, plasma levels of TAT, TM, and t-PAIC may predict the development of SAP, and the TAT + TM + t-PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP.
Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and western blot analyses confirmed the upregulation of both Grp78 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94, chop, Atf6, Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride.
Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.
Introduction: Pigs are often used to study the intestinal development of newborns, particularly as preterm pig models that mimic the intestinal growth of human preterm infants. Neonatology's study of delivery mode's impact on neonatal development is crucial. Methods: We established 14 newborn pigs delivered via cesarean sections (C-section, at 113 days of gestational age, CS group) and 8 naturally born pigs were used as controls (at 114 days of gestational age, NF group). The impact of two alternative delivery procedures (C-section and natural birth) on the levels of short-chain fatty acids (SCFAs) and organic acids in the hepatic and intestines of newborn pigs were compared using metabolomics. The underlying molecular pathways are examined at the "protein-metabolite" level by integrating proteomic data. Results: The findings demonstrated that the mode of delivery changed the metabolism of SCFAs in newborn pigs, perhaps by affecting the physiology levels of cyclic intermediates such as lactate and malate in the pyruvate metabolic pathway. Additionally, by participating in the fatty acid metabolism pathway, two distinct proteins (FASN and HSD17B4) may impact the physiological concentration of these tiny metabolites. Discussion: In conclusion, this study provided reliable animal model data for understanding the physiological SCFA metabolic information and its affecting mechanism of large-gestational age preterm infants.
Introduction: Systemic dimorphic fungi pose a significant public health challenge, causing over one million new infections annually. The dimorphic transition between saprophytic mycelia and pathogenic yeasts is strongly associated with the pathogenesis of dimorphic fungi. However, despite the dynamic nature of dimorphic transition, the current omics studies focused on dimorphic transition primarily employ static strategies, partly due to the lack of suitable dynamic analytical methods. Methods: We conducted time-course transcriptional profiling during the dimorphic transition of Talaromyces marneffei, a model organism for thermally dimorphic fungi. To capture non-uniform and nonlinear transcriptional changes, we developed DyGAM-NS (dynamic optimized generalized additive model with natural cubic smoothing). The performance of DyGAM-NS was evaluated by comparison with seven other commonly used time-course analysis methods. Based on dimorphic transition induced genes (DTIGs) identified by DyGAM-NS, cluster analysis was utilized to discern distinct gene expression patterns throughout dimorphic transitions of T. marneffei. Simultaneously, a gene expression regulatory network was constructed to probe pivotal regulatory elements governing the dimorphic transitions. Results: By using DyGAM-NS, model, we identified 5,223 DTIGs of T. marneffei. Notably, the DyGAM-NS model showcases performance on par with or superior to other commonly used models, achieving the highest F1 score in our assessment. Moreover, the DyGAM-NS model also demonstrates potential in predicting gene expression levels throughout temporal processes. The cluster analysis of DTIGs suggests divergent gene expression patterns between mycelium-to-yeast and yeast-to-mycelium transitions, indicating the asymmetrical nature of two transition directions. Additionally, leveraging the identified DTIGs, we constructed a regulatory network for the dimorphic transition and identified two zinc finger-containing transcription factors that potentially regulate dimorphic transition in T. marneffei. Discussion: Our study elucidates the dynamic transcriptional profile changes during the dimorphic transition of T. marneffei. Furthermore, it offers a novel perspective for unraveling the underlying mechanisms of fungal dimorphism, emphasizing the importance of dynamic analytical methods in understanding complex biological processes.
BACKGROUND: The incidence of male breast cancer has been increasing in recent years; however, the long-term survival outcomes of diagnosed patients remain uncertain. This study was designed to evaluate the conditional survival of male breast cancer patients and to predict the future survival of patients through the conditional nomogram, to provide important suggestions for clinical decision-making. METHODS: Retrospective data from the SEER database included 3600 male breast cancer patients, divided into training and validation groups (7â :â 3 ratio). Overall survival rates were calculated using Kaplan-Meier analysis. Conditional survival analysis described survival at specific years. Time-dependent multivariate Cox analysis identified prognostic factors' impact. The conditional survival nomogram model predicted real-time survival rates. RESULTS: Over time, the 5-year real-time survival rate of patients gradually improved, increasing from 70.5 to 74.8, 79.4, 85.8, and 92.9% (respectively, representing 5-year survival rates of 1-4â years after diagnosis). In addition, the improvement in conditional survival rate CS5 showed a nonlinear trend. After 5â years of diagnosis, age, tumor size, and tumor stage had a sustained impact on patient prognosis. Finally, a conditional survival nomogram was constructed to predict the 10-year survival rate in real time. CONCLUSION: Five years after diagnosis, the conditional survival rate of male patients with breast cancer has improved, but it is not nonlinear. In the first 5â years after diagnosis, patients with older age, larger tumor size, poorer tumor stage, and distant metastasis should be actively followed up and treated to improve their long-term survival.
To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.
In view of the excellent prospects of gene therapy and the potential safety and immunogenicity issues challenged by viral vectors, it is of great significance to develop a nonviral vector with low toxicity and low cost. In this work, we report a chitosan nanoparticle (CSNP) to be used as a gene vector prepared through a facile solvent-exchange strategy. Chitosan is first dissolved in ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIM Ac), and then, the solvent is exchanged with water/phosphate-buffered saline (PBS) to remove ionic liquid, forming a final CSNP dispersion after ultrasonication. The prepared CSNP shows a positive surface charge and can condense green fluorescent protein-encoding plasmid (pGFP) at weight ratios (CSNP/pGFP) of 5/1 or higher. Dynamic light scattering size and ζ-potential characterization and gel retardation results confirm the formation of CSNP/pGFP complexes. Compared with plain pGFP, efficient cellular internalization and significantly enhanced green fluorescent protein (GFP) expression are observed by using CSNP as a plasmid vector. Benefitting from the intrinsic biocompatibility, low cost, low immunogenicity, and abundant sources of chitosan, as well as the facile preparation and the efficient gene transfection capacity of CSNP, it is believed that this CSNP could be used as a nonviral gene vector with great clinical translational potentials.
Chitosan , Green Fluorescent Proteins , Nanoparticles , Plasmids , Solvents , Chitosan/chemistry , Nanoparticles/chemistry , Green Fluorescent Proteins/chemistry , Green Fluorescent Proteins/genetics , Humans , Solvents/chemistry , Plasmids/chemistry , Plasmids/genetics , Gene Transfer Techniques , Transfection/methods , Particle Size , HeLa Cells
The detection of carcinoembryonic antigen (CEA) holds significant importance in the early diagnosis of cancer. However, current methods are hindered by limited accessibility and specificity. This study proposes a rapid and convenient Cas12a-based assay for the direct detection of CEA in clinical serum samples, aiming to address these limitations. The protocol involves a rolling machine operation, followed by a 5-min Cas12a-mediated cleavage process. The assay demonstrates the capability to detect human serum with high anti-interference performance and a detection limit as low as 0.2 ng/mL. The entire testing procedure can be accomplished in 75 min without centrifugation steps, and successfully reduced the limit of detection of traditional DNA walking machine by 50 folds. Overall, the testing procedure can be easily implemented in clinical settings.
Biosensing Techniques , CRISPR-Cas Systems , Carcinoembryonic Antigen , DNA , Limit of Detection , Carcinoembryonic Antigen/blood , Humans , Biosensing Techniques/methods , DNA/chemistry , Endodeoxyribonucleases , Nucleic Acid Amplification Techniques/methods , CRISPR-Associated Proteins , Bacterial Proteins/genetics
Rechargeable Li-CO2 batteries are considered as a promising carbon-neutral energy storage technology owing to their ultra-high energy density and efficient CO2 capture capability. However, the sluggish CO2 reduction/evolution kinetics impedes their practical application, which leads to huge overpotentials and poor cyclability. Multi-element transit metal oxides (TMOs) are demonstrated as effective cathodic catalysts for Li-CO2 batteries. But there are no reports on the integration of defect engineering on multi-element TMOs. Herein, the oxygen vacancy-bearing Li-Ni-Co-Mn multi-oxide (Re-NCM-H3) catalyst with the α-NaFeO2-type structure is first fabricated by annealing the NiCoMn precursor that derived from spent ternary LiNi0.8Co0.1Mn0.1O2 cathode, in H2 at 300 °C. As demonstrated by experimental results and theory calculations, the introduction of moderate oxygen vacancy has optimized electronic state near the Fermi level (Ef), eventually improving CO2 adsorption and charge transfer. Therefore, the Li-CO2 batteries with Re-NCM-H3 catalyst deliver a high capacity (11808.9 mAh g-1), a lower overpotential (1.54 V), as well as excellent stability over 216 cycles at 100 mA g-1 and 165 cycles at 400 mA g-1. This study not only opens up a sustainable application of spent ternary cathode, but also validates the potential of multi-element TMO catalysts with oxygen defects for high-efficiency Li-CO2 batteries.
Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.
Objective: Primary squamous cell thyroid carcinoma (PSCTC) is an extremely rare carcinoma, accounting for less than 1% of all thyroid carcinomas. However, the factors contributing to PSCTC outcomes remain unclear. This study aimed to identify the prognostic factors and develop a prognostic predictive model for patients with PSCTC. Methods: The analysis included patients diagnosed with thyroid carcinoma between 1975 and 2016 from the Surveillance, Epidemiology, and End Results database. Prognostic differences among the 5 pathological types of thyroid carcinomas were analyzed. To determine prognostic factors in PSCTC patients, the Cox regression model and Fine-Gray competing risk model were utilized. Based on the Fine-Gray competing risk model, a nomogram was established for predicting the prognosis of patients with PSCTC. Results: A total of 198,757 thyroid carcinoma patients, including 218 PSCTC patients, were identified. We found that PSCTC and anaplastic thyroid cancer had the worst prognosis among the 5 pathological types of thyroid carcinoma (P < .001). According to univariate and multivariate Cox regression analyses, age (71-95 years) was an independent risk factor for poorer overall survival and disease-specific survival in PSCTC patients. Using Fine-Gray regression analysis, the total number of in situ/malignant tumors for patient (Number 1) (≥2) was identified as an independent protective factor for prognosis of PSCTC. The area under the curve, the concordance index (C-index), calibration curves and decision curve analysis revealed that the nomogram was capable of predicting the prognosis of PSCTC patients accurately. Conclusion: The competing risk nomogram is highly accurate in predicting prognosis for patients with PSCTC, which may help clinicians to optimize individualized treatment decisions.
Carcinoma, Squamous Cell , Nomograms , SEER Program , Thyroid Neoplasms , Humans , Male , Female , Thyroid Neoplasms/pathology , Thyroid Neoplasms/mortality , Thyroid Neoplasms/diagnosis , Prognosis , Aged , Middle Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Adult , Risk Factors , Proportional Hazards Models , Risk Assessment , Neoplasm Staging , Kaplan-Meier Estimate
There is still considerable controversy about the relative risk of mycotoxin exposure associated with the consumption of organic and conventional cereals. Using validated protocols, we carried out a systematic literature review and meta-analyses of data on the incidence and concentrations of mycotoxins produced by Fusarium, Claviceps, Penicillium, and Aspergillus species in organic and conventional cereal grains/products. The standard weighted meta-analysis of concentration data detected a significant effect of production system (organic vs. conventional) only for the Fusarium mycotoxins deoxynivalenol, with concentrations â¼50% higher in conventional than organic cereal grains/products (p < 0.0001). Weighted meta-analyses of incidence data and unweighted meta-analyses of concentration data also detected small, but significant effects of production system on the incidence and/or concentrations of T-2/HT-2 toxins, zearalenone, enniatin, beauvericin, ochratoxin A (OTA), and aflatoxins. Multilevel meta-analyses identified climatic conditions, cereal species, study type, and analytical methods used as important confounding factors for the effects of production system. Overall, results from this study suggest that (i) Fusarium mycotoxin contamination decreased between the 1990s and 2020, (ii) contamination levels are similar in organic and conventional cereals used for human consumption, and (iii) maintaining OTA concentrations below the maximum contamination levels (3.0 µg/kg) set by the EU remains a major challenge.
Edible Grain , Food Contamination , Mycotoxins , Edible Grain/chemistry , Edible Grain/microbiology , Mycotoxins/analysis , Food Contamination/analysis , Fusarium/chemistry , Food, Organic/analysis , Food, Organic/microbiology
Phytochemical analysis of Chloranthus henryi var. hupehensis roots led to the identification of a new eudesmane sesquiterpenoid dimer, 18 new sesquiterpenoids, and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer that is assembled by a unique oxygen bridge (C11-O-C8') of two highly rearranged eudesmane-type sesquiterpenes with the undescribed C16 carbon framework. (+)-2 and (-)-2 were a pair of new skeleton dinorsesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures were elucidated using spectroscopic data, single-crystal X-ray diffraction analysis, and quantum chemical computations. In the LPS-induced BV-2 microglial cell model, 17 suppressed IL-1ß and TNF-α expression with EC50 values of 6.81 and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production in a dose dependent manner and without cytotoxicity. In subsequent mechanism studies, compounds 3, 16, and 17 could reduce IL-1ß and TNF-α production by inhibiting IKBα/p65 pathway activation.
Dose-Response Relationship, Drug , Plant Roots , Sesquiterpenes , Signal Transduction , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Plant Roots/chemistry , Signal Transduction/drug effects , Molecular Structure , Mice , Animals , Structure-Activity Relationship , Transcription Factor RelA/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Drug Discovery , NF-KappaB Inhibitor alpha/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification
Horizontal gene transfer (HGT) from one organism to another, according to some researchers, can be abundant in the evolution of species. A phylogenetic network is a network structure that describes the HGTs among species. Several studies have proposed methods to construct phylogenetic networks to predict HGTs based on parsimony values. Existing definitions of parsimony values for a phylogenetic network are based on the assumption that each gene site or segment evolves independently along different trees in the network. However, in the current study, we define a novel parsimony value, denoted the p definition, for phylogenetic networks, considering that a gene as a whole typically evolves along a tree. Using Simulated Annealing, a new method called the Phylogeny with Simulated Annealing (PSA) algorithm is proposed to search for an optimal network based on the p definition. The PSA method is tested on the simulated data. The results reveal that the parsimonious networks constructed using PSA can better represent the evolutionary relationships of species involving HGTs. Additionally, the HGTs predicted using PSA are more accurate than those predicted using other methods. The PSA algorithm is publicly accessible at http://github.com/imustu/sap.
Background: Major depressive disorder (MDD) is a widespread health issue in many countries, which has an extremely negative impact on the health of children and adolescents in particular. In the context of depression and metabolic disorders, dyslipidemia and metabolism-related problems become more prominent comorbidities. However, they continue to be the main barrier to the successful recovery of the clinical progress. In this study we investigated the rate of dyslipidemia, additional risk factors among Chinese children and adolescents with MDD, and association of the suicidal behavior with lipid levels. Methods: The study took 756 people from the Third People's Hospital of Fuyang between January 2020 and December 2021, aged between 8 and 18, with major depressive disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We determined the FBG (fasting blood glucose) and lipid parameters in all subjects and also investigated the history of suicidal ideation, the cases of attempted suicide, and the scores of depressive symptoms. Sociodemographic and clinical data were gathered and analyzed using the SPSS-23.0 version. Results: The prevalence of hypercholesterolemia, hypertriglyceridemia, high LDL-C, and low HDL-C were 5.42 % (41/756), 10.58 % (80/756), 3.84 % (29/756) and 5.42 % (41/756) respectively. For hypercholesterolemia and hypertriglyceridemia, they were positive associated with suicidal ideation and suicide attempts, and the positive correlation is shown between low HDL-C levels and suicide attempts. Nevertheless, non-ideation and inversely suicidal attempts were not discovered among high-LDL-C subjects. Logistic analysis showed that high levels of FBG (OR = 2.86, 95 % CI: 1.31-6.25, P = 0.008) and worse LDL-C (OR = 357.82, 95 % CI: 66.16-1935.10, P < 0.001) are the independent associated factors for hypercholesterolemia. More hospitalizations (OR = 1.89, 95 % CI: 1.07-3.35, P = 0.028), obesity (OR = 2.55, 95 % CI: 1.25-5.18, P = 0.010), high levels of TC (OR = 2.15, 95 % CI: 1.03-4.48, P = 0.042), and higher doses of antidepressants (OR = 1.02, 95 % CI: 1.00-1.04, P = 0.029) were independently associated factors for hypertriglyceridemia, while high levels of HDL-C (OR = 0.11, 95 % CI: 0.04-0.31, P < 0.001) were protective factors. In addition, high levels of TC (OR = 113.94, 95 % CI: 20.01-648.85) were statistically different (P < 0.001) and suggested that the factor was significantly related to high LDL-C. Meanwhile, older age (OR = 1.25, 95 % CI: 1.02-1.52, P = 0.030) and high levels of TG (OR = 3.00, 95 % CI: 1.98-4.55, P < 0.001) were independent factors contributing to low HDL-C. Conclusion: The high prevalence of dyslipidemia in childhood and adolescence among children and adolescents with depressive disorder has become a public health issue. Hypercholesterolemia and hypertriglyceridemia showed a positive correlation with suicidal thoughts and suicidal attempts. Monitoring the incidence of suicidal thoughts and attempts among them would carry some predictor meaning in therapy and for jumping back to health.
Calreticulin (CRT) is a calcium-binding endoplasmic reticulum (ER) protein that has been identified for multiple cellular processes, including protein folding, regulation of gene expression, calcium (Ca2+) storage and signaling, regeneration, and stress responses. However, the lack of information about this protein family in tomato species highlights the importance of functional characterization. In the current study, 21 CRTs were identified in four tomato species using the most recent genomic data and performed comprehensive bioinformatics and SlCRT expression in various tissues and treatments. In the bioinformatics analysis, we described the physiochemical properties, phylogeny, subcellular positions, chromosomal location, promoter analysis, gene structure, motif distribution, protein structure and protein interaction. The phylogenetic analysis classified the CRTs into three groups, consensus with the gene architecture and conserved motif analyses. Protein structure analysis revealed that the calreticulin domain is highly conserved among different tomato species and phylogenetic groups. The cis-acting elements and protein interaction analysis indicate that CRTs are involved in various developmental and stress response mechanisms. The cultivated and wild tomato species exhibited similar gene mapping on chromosomes, and synteny analysis proposed that segmental duplication plays an important role in the evolution of the CRTs family with negative selection pressure. RNA-seq data analysis showed that SlCRTs were differentially expressed in different tissues, signifying the role of calreticulin genes in tomato growth and development. qRT-PCR expression profiling showed that all SlCRTs except SlCRT5 were upregulated under PEG (polyethylene glycol) induced drought stress and abscisic acid (ABA) treatment and SlCRT2 and SlCRT3 were upregulated under salt stress. Overall, the results of the study provide information for further investigation of the functional characterization of the CRT genes in tomato.
Background: Gallbladder cancer (GBC) is a common malignant tumor of the biliary system. It is characterised by insidious onset, rapid progression and poor prognosis. Symptoms often indicate advanced or late-stage disease, with a 5-year survival rate of only 5-15%. Case Description: We present a case study of a patient with GBC who had a tumor mutation burden (TMB) of 32.5/MB (≥10 muts/MB). The patient received mFOLFIRINOX as first-line chemotherapy, which demonstrated significant efficacy. After stabilizing the disease, a sequential chemotherapy regimen was chosen. This regimen combined the immune checkpoint inhibitor (ICI) toripalimab (JS001), a humanised IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1), with S-1 therapy, an oral fluoropyrimidine derivative. However, this treatment did not provide any significant clinical benefit for the patient. Therefore, we hypothesise that combining immunotherapy with chemotherapy may be more effective as a first line treatment for high-TMB advanced GBC. This hypothesis needs to be validated in large-scale clinical studies. Conclusions: In summary, mFOLFIRINOX is a safe and effective first-line chemotherapy regimen for advanced GBC. The timing of combining immunotherapy with chemotherapy requires careful consideration. Further clinical trials involving immunotherapy in advanced GBC are necessary to identify biomarkers that can guide clinical decisions.
Lung cancer is one of the most frequently diagnosed cancers worldwide, associated with a poor survival rate. Taxol (Paclitaxel) is commonly used as a chemotherapeutic treatment for advanced lung cancers. While Taxol has improved clinical outcomes for lung cancer patients, a significant number of them develop resistance to Taxol, resulting in treatment failure. The role of the long noncoding RNA HCG18 in lung cancer and Taxol resistance has not yet been fully understood. To investigate this, we examined the expression of HCG18 and miR-34a-5p in lung tumors and normal lung tissues using qRT-PCR. We also assessed Taxol resistance through cell viability and apoptosis assays. Through the starBase online service, we analyzed the interactions between lncRNA and mRNA as well as miRNA and mRNA. We further validated the association between lncRNA and miRNA through luciferase and RNA pull-down assays. Our findings demonstrated that HCG18 was significantly upregulated in lung cancer tissues compared to normal lung tissues. Silencing HCG18 increased the sensitivity of lung cancer cells to Taxol. Additionally, our study established a Taxol-resistant cell line and observed a substantial upregulation of HCG18 in Taxol-resistant lung cancer cells. Bioinformatic analysis predicted that HCG18 could bind to miR-34a-5p, forming a competing endogenous RNA network, which was confirmed through luciferase assay. We found that miR-34a-5p was downregulated in lung cancer tissues and negatively correlated with Taxol resistance, as it directly bound to the 3'UTR region of HDAC1. Further results showed that inhibition of HCG18 significantly increased miR-34a-5p expression and sensitized lung cancer cells to Taxol. This sensitization could be reversed by inhibiting miR-34a-5p. Finally, we demonstrated in a xenograft mouse model that inhibition of HCG18 sensitized Taxol-resistant lung cancer cells to Taxol treatment by modulating the miR-34a-5p-HDAC1 axis. In conclusion, our in vitro and in vivo results uncover a novel molecular mechanism by which HCG18 promotes Taxol resistance through modulation of the miR-34a-5p/HDAC1 axis. These findings contribute to the diagnosis and treatment of chemo-resistant lung cancer.
