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Frontiers in Immunology 2024Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung...
Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.
Topics: Humans; Colorectal Neoplasms; Prognosis; Adenocarcinoma; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Female; Cell Line, Tumor; Male; Cell Proliferation; Gene Expression Profiling; Transcriptome; Nomograms; Octamer Transcription Factor-3; Cell Movement
PubMed: 38962013
DOI: 10.3389/fimmu.2024.1344637 -
Frontiers in Immunology 2024
Topics: Humans; Necroptosis; Animals; Translational Research, Biomedical
PubMed: 38962001
DOI: 10.3389/fimmu.2024.1441901 -
Heliyon Jun 2024Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics....
Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear. This study seeks to investigate the potential influence of antibiotics on ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Here, we report a previously unrecognized role of ciprofloxacin in inhibiting ferroptosis in human PDAC cells. Mechanistically, ciprofloxacin suppresses erastin-induced endoplasmic reticulum (ER) stress through the activating transcription factor 6 (ATF6) and ER to nucleus signaling 1 (ERN1) pathway. Excessive ER stress activation can trigger glutathione peroxidase 4 (GPX4) degradation through autophagic mechanisms. In contrast, ciprofloxacin enhances the protein stability of GPX4, a crucial regulator that suppresses ferroptosis by inhibiting lipid peroxidation. Thus, our study demonstrates the anti-ferroptotic role of ciprofloxacin, highlighting the importance of careful consideration when contemplating the combination of ciprofloxacin with specific ferroptosis inducers in PDAC patients.
PubMed: 38961954
DOI: 10.1016/j.heliyon.2024.e32571 -
Heliyon Jun 2024Street foods are one of the highest contributors to foodborne illness in most developing economies around the world. In Ghana, diarrhoeal diseases, which are usually...
Street foods are one of the highest contributors to foodborne illness in most developing economies around the world. In Ghana, diarrhoeal diseases, which are usually food or waterborne, are among the top ten causes of death. Most street food safety risks are avoidable when all food safety regulations are complied with. This paper identified and examined the barriers to the implementation of street food safety regulations in Ghana. A qualitative research approach was adopted by collecting data from nine focus group discussion sessions involving a total of 94 participants and five key informant interviews. The research uncovered three broad but interconnected categories of challenges to ensuring and sustaining street food safety: street vendor anonymity as a central challenge; poor trust in the regulatory system as root challenges; and vendor practices that risk the safety of street foods as consequential challenges. These findings have tangible policy implications. To best serve their purpose, policymakers need to understand these food safety challenges and ensure that food safety policies are responsive to the challenges.
PubMed: 38961945
DOI: 10.1016/j.heliyon.2024.e32190 -
Heliyon Jun 2024Long-time hypoxia induced cardiomyocyte apoptosis is an important mechanism of myocardial ischemia (MI) injury. Interestingly, long noncoding RNA myocardial...
Long-time hypoxia induced cardiomyocyte apoptosis is an important mechanism of myocardial ischemia (MI) injury. Interestingly, long noncoding RNA myocardial infarction-associated transcript (LncMIAT) has been involved in the regulation of MI injury; however, the underlying mechanism by which LncMIAT affects the progression of hypoxia-induced cardiomyocyte apoptosis remains unclear. In the present study, hypoxia was found to promote cardiomyocyte apoptosis through an increased expression of LncMIAT . Biological investigations and dual-luciferase gene reporter assay further revealed that LncMIAT was able to bind with miR-708-5p to upregulate the p53-mediated cell death of the cardiomyocytes. Silencing of LncMIAT or overexpression of miR-708-5p led to a significant reduction in p53-mediated cardiomyocyte apoptosis. The methylated RNA immunoprecipitation (MeRIP)-qPCR results showed that hypoxia exerted its effects on LncMIAT through AKLBH5-N-methyladenosine (mA) methylation and therefore hypoxia was shown to trigger HL-1 cardiomyocyte apoptosis via the mA methylation-mediated LncMIAT/miR-708-5p/p53 axis. Silencing of AKLBH5 significantly alleviated the mA methylation-mediated LncMIAT upregulation and p53-mediated cardiomyocyte apoptosis, while promoted miR-708-5p expression. Taken together, the present study highlighted that LncMIAT could act as a key biological target during hypoxia-induced cardiomyocyte apoptosis. In addition, it was shown that hypoxia could promote cardiomyocyte apoptosis through regulation of the mA methylation-mediated LncMIAT/miR-708-5p/p53 signaling axis.
PubMed: 38961902
DOI: 10.1016/j.heliyon.2024.e32455 -
Heliyon Jun 2024Traffic accidents are caused by several interacting risk factors. This study aimed to investigate the interactions among risk factors associated with death at the...
AIM
Traffic accidents are caused by several interacting risk factors. This study aimed to investigate the interactions among risk factors associated with death at the accident scene (DATAS) as an indicator of the crash severity, for pedestrians, passengers, and drivers by adopting "Logic Regression" as a novel approach in the traffic field.
METHOD
A case-control study was designed based on the police data from the Road Traffic Injury Registry in northwest of Iran during 2014-2016. For each of the pedestrians, passengers, and drivers' datasets, logic regression with "logit" link function was fitted and interactions were identified using Annealing algorithm. Model selection was performed using the cross-validation and the null model randomization procedure.
RESULTS
regarding pedestrians, "The occurrence of the accident outside a city in a situation where there was insufficient light" (OR = 6.87, -value<0.001) and "the age over 65 years" (OR = 2.97, -value<0.001) increased the chance of DATAS "Accidents happening in residential inner-city areas with a light vehicle, and presence of the pedestrians in the safe zone or on the non-separate two-way road" combination lowered the chance of DATAS (OR = 0.14, -value<0.001). For passengers, "Accidents happening in outside the city or overturn of the vehicle" combination (OR = 8.55, -value<0.001), and "accidents happening on defective roads" (OR = 2.18, value<0.001) increased the odds of DATAS; When "driver was not injured or the vehicle was two-wheeled", chance of DATAS decreased for passengers (OR = 0.25, p-value<0.001). The odds of DATAS were higher for "drivers who had a head-on accident, or drove a two-wheeler vehicle, or overturned the vehicle" (OR = 4.03, P-value<0.001). "Accident on the roads other than runway or the absence of a multi-car accident or an accident in a non-residential area" (OR = 6.04, P-value<0.001), as well "the accident which occurred outside the city or on defective roads, and the drivers were male" had a higher risk of DATAS for drivers (OR = 5.40, P-value<0.001).
CONCLUSION
By focusing on identifying interaction effects among risk factors associated with DATAS through logic regression, this study contributes to the understanding of the complex nature of traffic accidents and the potential for reducing their occurrence rate or severity. According to the results, the simultaneous presence of some risk factors such as the quality of roads, skill of drivers, physical ability of pedestrians, and compliance with traffic rules play an important role in the severity of the accident. The revealed interactions have practical significance and can play a significant role in the problem-solving process and facilitate breaking the chain of combinations among the risk factors. Therefore, practical suggestions of this study are to control at least one of the risk factors present in each of the identified combinations in order to break the combination to reduce the severity of accidents. This may have, in turn, help the policy-makers, road users, and healthcare professionals to promote road safety through prioritizing interventions focusing on effect size of simultaneous coexistence of crash severity determinants and not just the main effects of single risk factors or their simple two-way interactions.
PubMed: 38961891
DOI: 10.1016/j.heliyon.2024.e32469 -
Nanotheranostics 2024A cutting-edge non-invasive cancer treatment method called boron neutron capture therapy (BNCT) allows for the removal of cancerous tumor cells with the least possible... (Review)
Review
A cutting-edge non-invasive cancer treatment method called boron neutron capture therapy (BNCT) allows for the removal of cancerous tumor cells with the least possible damage to healthy tissue. It involves the exposure of cancer cells with low-energy thermal neutrons, boron-10 (B) cellular uptake causes cancer cell death by producing alpha particles and recoiling lithium-7 ( Li) nuclei. Despite positive outcomes from clinical trials conducted all around the world, these substances have relatively limited tumor selectivity or low boron content per molecule. The development of new boron delivery agents with more selectivity and enhanced boron loading would advance this technique and promote its use in clinics as a primary cancer treatment. As peptide-binding cell surface receptors are typically overexpressed on cancer cells, they can be seen as interesting targets for targeted tumor therapy. The attachment of meta-carboranes to peptide conjugates that target tumor cells specifically by their overexpressed receptors may be a method to get around these problems. A state-of-the-art overview of current developments in the application of BNCT for cancer targeted therapy via peptide conjugation is the goal of this review.
Topics: Boron Neutron Capture Therapy; Humans; Neoplasms; Peptides; Animals
PubMed: 38961887
DOI: 10.7150/ntno.95251 -
Nanotheranostics 2024Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac... (Review)
Review
Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.
Topics: Humans; Antineoplastic Agents; Cardiotoxicity; Nanomedicine; Theranostic Nanomedicine; Animals; Heart Diseases; Neoplasms; Nanoparticles
PubMed: 38961885
DOI: 10.7150/ntno.96846 -
International Journal of Reproductive... 2024Teenage pregnancy is a global public health challenge, and it is a major contributor to the high maternal and neonatal morbidity and mortality rates reported in...
Teenage pregnancy is a global public health challenge, and it is a major contributor to the high maternal and neonatal morbidity and mortality rates reported in sub-Saharan Africa and Uganda. However, there is a paucity of data regarding pregnancy outcomes and their associated factors among teenagers in Uganda. The purpose of this study was to determine the prevalence and factors associated with pregnancy outcomes among teenagers who delivered at a National Referral Hospital in Kampala, Uganda. This cross-sectional study was conducted among teenage mothers who delivered at a National Referral Hospital in Kampala, Uganda. Consecutive participant recruitment was done for those who fulfilled the eligibility criteria. The outcomes of interest included adverse maternal outcome with obstructed labor being used as a proxy and adverse fetal outcomes with birth asphyxia used as a proxy. Logistic regression analysis was used to determine the association between independent and dependent variables with a 5% level of statistical significance ( = 0.05). Teenage pregnancy was associated with adverse maternal outcomes which included obstructed labor (18%) and preterm labor (5.5%). There were no maternal deaths during the study period. Adverse fetal outcomes observed in this study population included low birth weight (83%), birth asphyxia (18%), and stillbirth (4%). The only factor associated with adverse maternal outcome was gestational age where teenage mothers had 4 times likelihood of delivering before 37 weeks. Relatedly, teenage mothers had an 81% chance of having a preterm birth. Teenage pregnancy was generally not associated with adverse maternal or fetal outcomes except for preterm birth. The reasons for adverse pregnancy outcomes may reflect a combination of gynecological and biological immaturity, as well as adverse socioeconomic pressures.
PubMed: 38961884
DOI: 10.1155/2024/6975966 -
JHEP Reports : Innovation in Hepatology Jul 2024Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of...
BACKGROUND & AIMS
Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed.
METHODS
Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events.
RESULTS
In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches ( = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; = 0.002).
CONCLUSIONS
Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors.
IMPACT AND IMPLICATIONS
Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.
PubMed: 38961853
DOI: 10.1016/j.jhepr.2024.101075