A Systematic Review of Cognitive Impairment in Individuals With Colorectal Cancer.

PROBLEM IDENTIFICATION: Patients with colorectal cancer (CRC) encounter varying degrees of objective and subjective cognitive impairment. The prevalence of objective and subjective cognitive impairment, factors affecting cognitive impairment, and interventions are presented in this review. LITERATURE SEARCH: The CINAHL Plus®, Cochrane Library, Embase®, PsycINFO®, PubMed®, and CNKI databases were systematically searched from the time of the database's establishment to May 2023. Manual searches for the relevant articles in the literature's references were also conducted. DATA EVALUATION: The results were independently assessed by two reviewers. SYNTHESIS: 25 studies were included. The prevalence of cognitive impairment in individuals with CRC was measured differently according to study designs. A model of factors contributing to cognitive impairment guided the integration of factors, including cancer treatments, psychosocial factors, and physical and emotional health conditions. Incorporated intervention programs could be integrated between objective and subjective aspects. Interventions relieved cognitive impairment in individuals with CRC. IMPLICATIONS FOR NURSING: The results of this review supported enhanced assessment and monitoring of cognitive impairment, particularly subjective cognitive impairment.

A couple-based dyadic coping intervention for colorectal cancer patient-spousal caregiver dyads: A randomized controlled study.

PURPOSE: To evaluate the clinical effects of a couple-focused dyadic coping intervention in colorectal cancer (CRC) couples. METHODS: The study was a single-blinded randomized controlled study which 226 CRC couples were recruited and randomized to either the intervention (N = 113) or the control (N = 113) group. All couples received usual care while the six-week dyadic coping intervention was provided to the intervened couples in psycho-education and skill training methods through face-to-face combined with telephone formats. Measurement data, including dyadic coping, marital satisfaction, quality of life and psychological well-being were collected at pre- and post-intervention periods. And multilevel model (MLM) was applied to analyze the effects of the intervention and the role tendency. RESULTS: A total of 173 couples completed the program and post-intervention evaluation. The retention rate was 76.5%. Results from MLM showed that the dyadic coping intervention is effective in promoting levels of dyadic coping (P < 0.001), marital satisfaction (P = 0.042), mental health (P = 0.006), and positive psychological well-being (P < 0.001), and alleviating depression (P = 0.015) in CRC couples. For role tendency, the intervention found to be more effective in CRC spousal caregivers' positive psychological well-being compared to the patients (P = 0.037). CONCLUSION: The couple-based dyadic coping intervention is effective in promoting dyadic coping and improving psychological adjustment in CRC couples. More studies were needed to further evaluate the program and its long-term efficacy in the future. In addition, given the positive effects of the intervention, clinical nursing stuffs may consider implementing such intervention in their routine work while caring for CRC couples.

Structures and activation mechanism of the Gabija anti-phage system.

Prokaryotes have evolved intricate innate immune systems against phage infection1-7. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB8. GajA functions as a DNA endonuclease that is inactive in the presence of ATP9. Here, to explore how the Gabija system is activated for anti-phage defence, we report its cryo-electron microscopy structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP and Mg2+. GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the centre and the topoisomerase-primase (Toprim) domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gabija activation.

Advances in the Pathogenesis of Metabolic Liver Disease-Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the primary cause of death in cancer cases, with significant public health concern worldwide. Despite the overall decline in the incidence and mortality rates of HCC in recent years in recent years, the emergence of metabolic liver disease-related HCC is causing heightened concern, especially in countries like the United States, the United Kingdom, and P.R. China. The escalation of metabolic liver disease-related HCC is attributed to a combination of factors, including genetic predisposition, lifestyle choices, and changes in the living environment. However, the pathogenesis of metabolic liver disease-associated HCC remains imperfect. In this review, we encapsulate the latest advances and essential aspects of the pathogenesis of metabolic liver disease-associated HCC, including alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and inherited metabolic liver diseases.

Porphyrin-based covalent organic frameworks as doxorubicin delivery system for chemo-photodynamic synergistic therapy of tumors.

Photodynamic therapy (PDT) is a non-invasive treatment method that has garnered significant attention in recent years. Nanoparticle-based drug delivery systems can achieve targeted drug release, thereby significantly reducing side effects and enhancing therapeutic efficacy. In this study, a covalent organic framework (COF) with an approximately spherical structure connected by azo bonds was synthesized. The synthesized COF was utilized as a hypoxia-responsive carrier for doxorubicin (DOX) drug delivery and was modified with hyaluronic acid (HA). DOX@COF@HA exhibited a reactive release under hypoxic conditions. Under normal oxygen conditions, the release of DOX was 16.9 %, increasing to 60.2 % with the addition of sodium hydrosulfite. In vitro experiments revealed that the group combining photodynamic therapy with chemotherapy exhibited the lowest survival rates for 4T1 and MHCC97-L cells. In vivo experiments further validated the effectiveness of combination therapy, resulting in a tumor volume of only 33 mm3 after treatment, with no significant change in mouse weight during the treatment period. DOX@COF@HA nanoplatforms exhibit substantial potential in tumor treatment.

The effect of a couple-based posttraumatic growth intervention in supporting couples coping with colorectal cancer: A randomized controlled study.

OBJECTIVES: To promote posttraumatic growth (PTG) in colorectal cancer (CRC) couples, a couple-based PTG intervention was conducted, and the intervention had previously proved be feasible in CRC couples. The current study was conducted to validate the effects of intervention in CRC couples. METHOD: This is a randomized controlled study that included 174 CRC couples. All participants were randomized to either the intervention (usual care plus 5-week PTG intervention, n = 87) or the control group (usual care, n = 87). Data were collected from CRC couple dyads at baseline and immediately post-intervention periods. Primary outcome refers to positive changes, and secondary outcomes include marital satisfaction, quality of life (QOL), and anxiety and depression. Multilevel modeling was applied to analyze the intervention effects. RESULTS: Participants in the program showed increased PTG, marital satisfaction, and QOL both physically and mentally, and decreased levels of anxiety and depression over time. And spousal caregivers showed greater improvement in marital satisfaction and physical QOL compared with patients. In addition, significant intervention effects were shown in the participants' benefit finding, physical health and depressive symptoms. CONCLUSION: The study confirmed the effect of the PTG intervention on CRC couples' benefit finding, physical health and depressive symptoms. However, this study only measured outcome variables at two time-points. Future studies should add follow-up assessments to evaluate long-term effects of the intervention in CRC couples. REGISTRATION NUMBER: ChiCTR2300067809.

Single-Component Photochemical Afterglow Near-Infrared Luminescent Nano-Photosensitizers: Bioimaging and Photodynamic Therapy.

Long afterglow luminescence-guided photodynamic therapy (PDT) performs advantages of noninvasiveness, spatiotemporal controllability, and higher signal to noise ratio. Photochemical afterglow (PCA) system emitting afterglow in an aqueous environment is highly suitable for biomedical applications, but still faces the challenges of poor tissue penetration depth and responsive sensitivity. In this work, two novel compounds, Iso-TPA and ABEI-TPA, are designed and synthesized to integrate the PCA system as a single component by coupling near-infrared (NIR) photosensitizers with singlet oxygen cache units, respectively. Both compounds emit NIR afterglow based on photochemical reaction. ABEI-TPA exhibits higher photoluminescence quantum efficiency with nonconjugated linkage, while Iso-TPA with conjugated linkage possesses better reactive oxygen species generation efficiency to achieve stronger PCA and effective PDT, which is ascribed to stronger intramolecular charge transfer effect of Iso-TPA. Iso-TPA nanoparticles can achieve effective long-lasting NIR afterglow in vivo bioimaging up to 120 s with higher imaging resolution and outstanding PDT efficacy of tumor, exhibiting promising potential on bioimaging and therapy.

A scoping literature review of factors influencing cancer patients' self-perceived burden.

PURPOSE: A cancer diagnosis disrupts the peaceful lives and plans of patients and even their caregivers, and patients can easily feel burdened when they are being cared for by others. However, the influencing factors of self-perceived burden (SPB) have not been summarized, and related research is still in its infancy. This review explores factors related to the SPB of cancer patients and identifies future research directions. METHOD: A systematic search, including trolling through six electronic databases, was conducted to identity articles published in English and Chinese from January 2003 to April 2022, using key terms related to cancer patients' burden on others; a manual search was also performed on the articles' reference lists. RESULTS: Thirty-three articles were identified. The content was described into three groups: patient-related factors, caregiver-related factors, and family-related (financial) factors. Despite the heterogeneity, patients' physical/disease factors, psychological factors, social factors, caregiver type, quality of care provided, caregiver physical and psychological status, and financial factors were all correlated with SPB. CONCLUSIONS: This literature review shows that SPB imposes a huge burden on cancer patients, and that SPB in cancer patients is influenced by patient-related factors, caregiver-related factors, and family factors. These influencing factors directly or indirectly affect SPB. In addition, SPB is complex and studies related to its factors deserve a further detailed analysis based on the actual situation of the patients in order to make the results more accurate and relevant.

Upregulated Tß4 expression in inflammatory bowel disease impairs the intestinal mucus barrier by inhibiting autophagy in mice.

Disrupted intestinal barrier homeostasis is fundamental to inflammatory bowel disease. Thymosin ß4 (Tß4) improves inflammation and has beneficial effects in dry-eye diseases, but its effects on the intestinal mucus barrier remain unknown. Therefore, this study evaluated the underlying regulatory mechanisms and effects of Tß4 by examining Tß4 expression in a mouse model with dextran sodium sulfate (DSS)-induced colitis and colonic barrier damage. Additionally, we intraperitoneally injected C57BL/6 mice with Tß4 to assess barrier function, microtubule-associated protein 1 light chain 3 (LC3II) protein expression, and autophagy. Finally, normal human colon tissue and colon carcinoma cells (Caco2) were cultured to verify Tß4-induced barrier function and autophagy changes. Mucin2 levels decreased, microbial infiltration increased, and Tß4 expression increased in the colitis mouse model versus the control mice, indicating mucus barrier damage. Moreover, Tß4-treated C57BL/6 mice had damaged intestinal mucus barriers and decreased LC3II levels. Tß4 also inhibited colonic mucin2 production, disrupted tight junctions, and downregulated autophagy; these results were confirmed in Caco2 cells and normal human colon tissue. In summary, Tß4 may be implicated in colitis by compromising the integrity of the intestinal mucus barrier and inhibiting autophagy. Thus, Tß4 could be a new diagnostic marker for intestinal barrier defects.

Multiple myeloma with high expression of SLC7A11 is sensitive to erastin-induced ferroptosis.

Ferroptosis, a nonapoptotic form of cell death marked by iron-dependent peroxidation of phospholipids, is associated with the occurrence and progression of tumors. Erastin, a selective inhibitor of the cystine/glutamate transporter system Xc-, can induce the ferroptosis of cancer cells. Multiple myeloma (MM) has been reported to be insensitive to erastin-induced ferroptosis. However, we found the erastin sensitivity of different MM cells varied widely. Specifically, SLC7A11 abundance determined the sensitivity of MM cells to erastin-induced ferroptosis. MM cells expressing a high SLC7A11 level were more sensitive to erastin-induced ferroptosis than cells expressing a low level of SLC7A11. Moreover, the expression of SLC7A11 gradually increased with the progression of plasma cell dyscrasias. Survival analysis indicated that high levels of SLC7A11 predicted a poor prognosis for MM patients. Knocking down SLC7A11 expression significantly inhibited the proliferation of MM cells and induced ferroptotic cell death. Additionally, we revealed that the long noncoding RNA (lncRNA) SLC7A11-AS1 was a critical regulatory factor of SLC7A11 expression. SLC7A11-AS1 overexpression diminished SLC7A11 levels, leading to the ferroptosis of MM cells. In summary, our data show that heterogeneous SLC7A11 expression affects MM cell sensitivity to ferroptosis, providing a theoretical basis for improving the clinical treatment of MM.

Melittin alleviates sepsis-induced acute kidney injury by promoting GPX4 expression to inhibit ferroptosis.

OBJECTIVES: Melittin, the main component of bee venom, is a natural anti-inflammatory substance, in addition to its ability to fight cancer, antiviral, and useful in diabetes treatment. This study seeks to determine whether melittin can protect renal tissue from sepsis-induced damage by preventing ferroptosis and explore the protective mechanism. METHODS: In this study, we investigated the specific protective mechanism of melittin against sepsis-induced renal injury by screening renal injury indicators and ferroptosis -related molecules and markers in animal and cellular models of sepsis. RESULTS: Our results showed that treatment with melittin attenuated the pathological changes in mice with lipopolysaccharide-induced acute kidney injury. Additionally, we found that melittin attenuated ferroptosis in kidney tissue by enhancing GPX4 expression, which ultimately led to the reduction of kidney tissue injury. Furthermore, we observed that melittin enhanced NRF2 nuclear translocation, which consequently upregulated GPX4 expression. our findings suggest that melittin may be a potential therapeutic agent for the treatment of sepsis-associated acute kidney injury by inhibiting ferroptosis through the GPX4/NRF2 pathway. CONCLUSIONS: Our study reveals the protective mechanism of melittin in septic kidney injury and provides a new therapeutic direction for Sepsis-AKI.

A synergistic regulation works in matrix stiffness-driven invadopodia formation in HCC.

Growing evidence has suggested that increased matrix stiffness can significantly strengthen the malignant characteristics of hepatocellular carcinoma (HCC) cells. However, whether and how increased matrix stiffness regulates the formation of invadopodia in HCC cells remain largely unknown. In the study, we developed different experimental systems in vitro and in vivo to explore the effects of matrix stiffness on the formation of invadopodia and its relevant molecular mechanism. Our results demonstrated that increased matrix stiffness remarkably augmented the migration and invasion abilities of HCC cells, upregulated the expressions of invadopodia-associated genes and enhanced the number of invadopodia. Two regulatory pathways contribute to matrix stiffness-driven invadopodia formation together in HCC cells, including direct triggering invadopodia formation through activating integrin ß1 or Piezo1/ FAK/Src/Arg/cortactin pathway, and indirect stimulating invadopodia formation through improving EGF production to activate EGFR/Src/Arg/cortactin pathway. Src was identified as the common hub molecule of two synergistic regulatory pathways. Simultaneously, activation of integrin ß1/RhoA/ROCK1/MLC2 and Piezo1/Ca2+/MLCK/MLC2 pathways mediate matrix stiffness-reinforced cell migration. This study uncovers a new mechanism by which mechanosensory pathway and biochemical signal pathway synergistically regulate the formation of invadopodia in HCC cells.

Fecal miR-223 is a noninvasive biomarker for estimating Crohn's disease activity.

INTRODUCTION: MicroRNA-223 (miR-223) has emerged as a promising noninvasive biomarker for Crohn's disease (CD). However, it is unclear which tissue derived miRNA-223 can more accurately estimate CD disease activity. MATERIALS AND METHODS: To collect serum, terminal ileal mucosa biopsy and fecal samples from CD patients and healthy controls. The CD Activity Index (CDAI) score, Montreal classification, maintenance medicines, peripheral blood inflammatory markers, fecal calprotectin (FC) and the Simple Endoscopic Score for CD (SES-CD) were recorded. To compare the expression of miR-223 in the serum, intestinal tissue, and feces. RESULTS: MiR-223 expression levels in the serum, intestinal tissue and feces of CD patients were significantly higher than those of controls. The level of miR-223 in the serum, intestinal tissue and feces increased significantly in active CD patients compared with that in inactive CD patients. The levels of serum, intestinal tissue and fecal miR-223 were correlated with the CDAI. Serum miR-223 was also correlated with C-reactive protein (CRP) and IL-6, tissue miR-223 correlated with IL-6 and FC, and fecal miR-223 correlated with FC. In terms of the association with FC, fecal miR-223 had a higher Spearman r value than tissue miR-223. The area under the curve (AUC) values of serum, tissue and fecal miR-223 to diagnose CD were similar to those of CRP and FC (AUC > 0.8). The AUC values of tissue and fecal miR-223 to evaluate CD disease activity were 0.832 and 0.818, respectively, and were higher than serum miR-223, CRP and FC. Fecal miR-223 had a higher specificity of 92.3%. CONCLUSIONS: Fecal miR-223 might be a novel, noninvasive biomarker for estimating the disease activity of CD patients.

An integrated intervention programme for couples facing colorectal cancer: A randomized controlled trial.

BACKGROUND: Under the guidance of a preliminary Live with Love Conceptual Framework, a Caring for Couples Coping with Colorectal Cancer (4Cs: CRC) programme was designed specifically for colorectal cancer couples. The objectives of this study included examining the efficacy of the programme for couples adapting to colorectal cancer and comparing the effects of different intervention delivery modes (online, face-to-face and blended) on couple outcomes. METHODS: A four-arm randomized controlled trial was conducted among Chinese colorectal cancer couples. Couples were randomly assigned to an online intervention, a face-to-face intervention, a blended intervention or a control group. Self-efficacy, dyadic coping, communication and dyadic outcomes (physical and mental health, negative and positive emotions and marital satisfaction) were evaluated at baseline and 6 weeks later. Analysis of variance (ANOVA) and repeated measures ANOVA were employed to assess between-group differences and within-group effects in the four groups, respectively. RESULTS: A total of 179 couples completed the 6-week study and post-study assessments. The intervention showed generally medium-to-large effects across multiple measured outcomes, including self-efficacy, dyadic coping, communication, mental health, negative emotions and positive emotions for both patients and spouse caregivers. Additionally, interventions delivered through different modes produced equally significant effects on couple outcomes. CONCLUSIONS: The integrated intervention programme is effective in improving cancer adaptation in colorectal cancer couples. Long-term follow-up and a mix of quantitative and qualitative assessments are crucial for further evaluation of the programme. TRIAL REGISTRATION: Retroactive registration is under review.

Clickable Photoreactive ATP-Affinity Probe for Global Profiling of ATP-Binding Proteins.

Adenosine triphosphate (ATP) is the major energy carrier in organisms, and there are many cellular proteins that can bind to ATP. Among these proteins, kinases are key regulators in several cell signaling processes, and aberrant kinase signaling contributes to the development of many human diseases, including cancer. Hence, small-molecule kinase inhibitors have been successfully used for the treatment of various diseases. Since the ATP-binding pockets are similar for many kinases, it is very important to evaluate the selectivity of different kinase inhibitors. We report here a clickable ATP photoaffinity probe for the global profiling of ATP-binding proteins. After incubating the protein lysate with the ATP probe followed by ultraviolet (UV) irradiation, ATP-binding proteins were labeled with an alkyne handle for subsequent biotin conjugation through click chemistry. Labeled proteins were enriched with streptavidin beads, digested with trypsin, and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). More than 400 ATP-binding proteins, including approximately 200 kinases, could be identified in a single LC-MS/MS run in the data-dependent acquisition mode. We then applied this method to the analysis of targets of three selected ATP-competitive kinase inhibitors. We were able to successfully identify some of their reported target proteins from label-free quantification results and validated the results using Western blot analyses. Together, we developed a clickable ATP photoaffinity probe for proteome-wide profiling of ATP-binding proteins and demonstrated that this chemoproteomic method is amenable to high-throughput target identification of kinase inhibitors.

Mutual communication processes within Chinese colorectal cancer patient-spousal caregiver dyads: A qualitative study of taking gender into account.

PURPOSE: Mutual communication within cancer couples is a complex process. More research is needed to explore the complex process of mutual communication and its nuances presented by various factors in different culture contexts. Gender, a factor embedded in marital relationships, is an important consideration. We thus aim to explore the mutual communication process within Chinese colorectal cancer couples and take gender into account. METHODS: A qualitative study was conducted by interviewing 20 colorectal cancer patients and 15 spousal caregivers. Inductive thematic analysis was used to analyze the transcripts. RESULTS: Three themes (mutual communication and support interaction, communication quality, and foundation of mutual communication and collaboration) were developed. Gender was found to have specific impact on emotional disclosure and communication challenges. A preliminary framework of "smile" was constructed to demonstrate the relationship among the three themes and the relationships between the three themes and dyads' psychosocial adaptation to colorectal cancer. CONCLUSIONS: Study findings demonstrate complex mutual communication processes within colorectal cancer couples and the impact of gender. The findings will contribute to developing more effective colorectal cancer couple-based mutual communication interventions. Health practitioners are suggested to improve mutual communication within colorectal cancer couples in three aspects: relational topics, emotional disclosure and communication skills. Guiding couples to deal with each theme and the relationship among the themes simultaneously is helpful for them to return and smile to their normal life.

The impact of self-perceived burden, caregiver burden, and dyadic coping on negative emotions in colorectal cancer patient-spousal caregiver dyads: a dyadic analysis.

Objective: To explore the correlation between dyadic coping, self-perceived burden, caregiver burden, and anxiety/depression in colorectal cancer patient-spousal caregiver dyads. Methods: This study surveyed 200 colorectal cancer patient-spousal caregiver dyads from August 2022 to December 2022. It evaluated self-perceived burden (only for patients), caregiver burden (only for spousal caregivers), dyadic coping, anxiety, and depression. It analyzed data through Pearson's correlation and the actor-partner interdependence mediation model. Results: Self-perceived burden and caregiver burden were significantly associated with the anxiety/depression of both individuals in colorectal cancer patient-spousal caregiver dyads; patients' dyadic coping was associated with self-perceived burden and caregiver burden; caregivers' dyadic coping was only associated with patients' dyadic coping and depression. There was an actor-partner mediating effect of self-perceived burden between dyadic coping and anxiety/depression, but there was only a partner-mediating effect of caregiver burden between dyadic coping and anxiety/depression. Conclusion: This study confirmed the interrelationship between self-perceived burden, caregiver burden, dyadic coping, anxiety, and depression. Self-perceived burden and caregiver burden mediated the relationship between dyadic coping and anxiety/depression in colorectal cancer patient-spousal caregiver dyads. This suggests dynamic interventions for self-perceived burden and caregiver burden can be implemented to improve anxiety/depression in both partners based on maintaining healthy dyadic coping between colorectal cancer patient-spousal caregiver dyads.

Gender Differences in Psychosocial Outcomes and Coping Strategies of Patients with Colorectal Cancer: A Systematic Review.

(1) Background: Gender is an important factor impacting cancer experience. This review mainly aimed to summarize colorectal cancer (CRC) patients' gender differences in psychosocial outcomes and coping strategies. (2) Methods: Relevant studies were searched for in four electronic databases from 2007 to July 2023. And manual searching was performed on the included studies' reference lists to identify additional eligible studies. (3) Results: A total of 37 eligible articles were included in this review. These studies were conducted in 19 countries, and they targeted CRC patients at various treatment stages. Significant results showed that female patients tended to have more psychological distress, complex social functioning, and less sexual distress and to choose more positive coping strategies than male patients. But there was no gender difference in psychosocial outcomes and/or coping strategies in some studies, which implied that gender similarity also existed. (4) Conclusions: The findings support the fact that there are both gender differences and similarities in CRC patients' psychosocial outcomes and coping strategies. A perspective beyond the simple masculine-feminine binary improved our in-depth understanding of gender tendency. Importantly, taking gender tendency into account is critical for medical staff to provide more personalized support and communication interventions.

An epoxide-based covalent sensor to detect cardiac proteome aggregation in a cardio-oncology model.

Covalent sensors to detect and capture aggregated proteome in stressed cells are rare. Herein, we construct a series of covalent fluorogenic sensors for aggregated proteins by structurally modulating GFP chromophore and arming it with an epoxide warhead. Among them, P2 probe selectively modifies aggregated proteins over folded ones and turns on fluorescence as evidenced by biochemical and mass spectrometry results. The coverage of this epoxide-based covalent chemistry is demonstrated using different types of aggregated proteins. Finally, the covalent fluorescent sensor P2 allows for direct visualization and capture of aggregated proteome in stressed cardiomyocytes and cardiac tissue samples from a cardio-oncology mouse model. The epoxide-based covalent sensor developed herein may become useful for future chemical proteomics analysis of aggregated proteins to dissect the mechanism underlying cardio-oncology.