Explore the vast range of titles available.

While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

Objective. To explore the efficacy of sorafenib combined with interventional therapy on primary liver cancer (PLC) patients and its effect on serum AFP, VEGF, and GGT. Methods. 120 PLC patients admitted to our hospital from January 2016 to January 2020 were selected as the research object and divided into group A and group B according to the admission order, with 60 cases each. Interventional therapy was performed to both groups, and sorafenib was given to group A additionally to compare their treatment effect, survival, adverse reaction rate (ARR), and serum AFP, VEGF, and GGT levels. Results. After treatment, group A obtained significantly higher objective remission rate (ORR) and disease control rate (DCR) (p<0.05), higher one-year survival rate and two-year survival rate (p<0.05), lower ARR of skin reactions, gastrointestinal reactions, hepatorenal reactions, and hyperbilirubinemia (p<0.05), and lower serum AFP, VEGF, and GGT levels (p<0.001). Conclusion. The combination of sorafenib and interventional therapy can inhibit the growth and migration of PLC, improve the immune function, prolong the survival period of patients, and lower ARR, so it should be promoted in practice.

Background Triple-negative breast cancer (TNBC) remains clinically challenging due to its aggressiveness, limited targeted therapies, and absence of reliable prognostic biomarkers. Identifying TNBC-specific molecular drivers is critical for improving patient outcomes. Methods We employed an integrated multi-omics approach to analyze tumor and adjacent normal tissues from 4 TNBC and 4 non-TNBC patients via RNA sequencing (RNA-seq) and whole-exome sequencing (WES), complemented by an extensive analysis of 115 TNBC and 976 non-TNBC samples from The Cancer Genome Atlas (TCGA). Prognostic screening was performed to identify potential biomarkers correlated with patient survival. In vitro experimental validation was carried out in MDA-MB-231 TNBC cells, and immunohistochemistry was used to confirm protein expression levels. Results Weighted Gene Co-expression Network Analysis (WGCNA) and comparative WES analysis revealed that TNBC exhibited unique transcriptional modules enriched in DNA replication and heterochromatin organization, distinct somatic mutation landscapes, and alternative splicing patterns. Prognostic screening identified chloride intracellular channel 3 ( CLIC3 ) as the top risk factor for poor survival. In vitro experimental validation showed that CLIC3 knockdown significantly inhibited proliferation (CCK-8, colony formation , invasion and migration in MDA-MB-231 TNBC cells. Immunohistochemistry assay confirmed significantly higher CLIC3 protein expression in TNBC versus non-TNBC tissues. Conclusions CLIC3 is a TNBC-specific prognostic biomarker and therapeutic target. Its inhibition impedes TNBC aggressiveness, providing a foundation for targeted therapy development.

The fast-disintegrating capsules rapidly disintegrate in various physiological environments, ensuring therapeutic efficacy. The formulation of plant-based capsules with balanced mechanical and fast disintegration characteristics continues to present technical challenges in pharmaceutical development. In this study, natural marine polysaccharides were utilized to achieve both rapid disintegration and excellent mechanical properties by combining κ-Carrageenan (κ-C) and ι-Carrageenan (ι-C). Additionally, the selection of KCl + NaCl mixed coagulants, along with the evaluation of their types, mass fractions, and ratios, enhanced the mechanical properties and transmittance of the capsules. FTIR analysis revealed that the membrane with a 5:5 κ-C/ι-C ratio formed hydrogen bonds, which were beneficial to its fast disintegration. SEM analysis revealed a dense microstructure in this formulation, contributing to its improved mechanical properties. Finally, this study hypothesizes that the disintegration behaviors of the capsules exhibited significant pH dependence, with ion exudation predominating in pH 1.2 and pH 7.0 media, while swelling dominated under pH 4.5 and pH 6.8 media. The prepared carrageenan blend-based capsules exhibited fast disintegration properties while maintaining excellent mechanical and barrier properties, thereby broadening the application of plant-based capsules in the field of medicine.

Background The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration. Methods We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2′-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models. Results We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p. Conclusions Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p. Graphical abstract

Type 2 diabetes mellitus (T2DM) accounts for more than 90% of cases of diabetes mellitus, which is harmful to human health. Herein, neoagaro-oligosaccharides (NAOs) were prepared and their potential as a treatment of T2DM was evaluated in KunMing (KM) mice. Specifically, a T2DM mice model was established by the combination of a high-fat diet (HFD) and alloxan injection. Consequently, the mice were given different doses of NAOs (100, 200, or 400 mg/kg) and the differences among groups of mice were recorded. As a result of the NAOs treatment, the fasting blood glucose (FBG) was lowered and the glucose tolerance was improved as compared with the model group. As indicated by the immunohistochemistry assay, the NAOs treatment was able to ameliorate hepatic macrovesicular steatosis and hepatocyte swelling, while it also recovered the number of pancreatic β-cells. Additionally, NAOs administration benefited the antioxidative capacity in mice as evidenced by the upregulation of both glutathione peroxidase and superoxide dismutase activity and the significant reduction of the malondialdehyde concentration. Furthermore, NAOs, as presented by Western blotting, increased the expression of p-ERK1/2, p-JNK, NQO1, HO-1, and PPARγ, via the MAPK, Nrf2, and PPARγ signaling pathways, respectively. In conclusion, NAOs can be used to treat some complications caused by T2DM, and are beneficial in controlling the level of blood glucose and ameliorating the damage of the liver and pancreatic islands.

Cardiovascular diseases (CVDs) have been the leading cause of death in China. Depression and anxiety are recognized as significant risk factors for poor prognosis and disability among Chinese CVD patients. However, these mental health conditions have received limited clinical attention in the context of CVD management. To date, comprehensive national epidemiological data on the prevalence of depression and anxiety in cardiovascular clinics (CVCs) in China are lacking. The present study aims to describe the prevalence, recognition and therapeutic inequity in CVCs so as to improve the overall health outcomes of CVD patients. A multicenter, cross-sectional study was conducted across secondary and tertiary hospitals in China (January 2021 to December 2022), enrolling 1049 CVD patients from CVCs consecutively. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Sociodemographic and clinical data were collected via standardized questionnaires. Risk factors were analyzed by multivariable logistic regression, meanwhile recognition rates and treatment inequities were systematically evaluated. The pooled prevalence of depression and anxiety were 61.4% and 53.4% respectively, with 23.9% exhibiting moderate-to-severe symptoms. The multivariable logistic regression analyses disclosed that residing in South Central China, usual activities impairment, as well as experiencing pain or discomfort in daily life were associated with the presence of both depression and anxiety among patients in CVCs. Alarmingly, only 41.5% of depressed patients and 44.1% of anxious patients were recognized; and fewer than 50% accessed guideline-recommended interventions (psycho-education or medications). Patients residing in South Central China, having moderate or severe mental symptoms and having anxiety and depression comorbidity were more likely to be recognized and treated by cardiologists. This first national study to demonstrate the “high burden-low care” paradox in Chinese CVCs highlights systemic gaps in mental health integration. Urgent implementation of collaborative care models is warranted, prioritizing standardized screening protocols and equity-focused interventions for vulnerable subgroups. These findings provide pivotal evidence for advancing Chinese CVD clinical guidelines to address the mental health crisis in cardiology. Trial registration: The trial was registered with ClinicalTrials.gov under the identifier NCT03225586 (Registration Date: 2017-07-19).

The main objective of this study was to explore the associations of family relationships and negative life events with depressive symptoms among Chinese adolescents. A cross-sectional study of 3081 middle school students was conducted in Ganzhou City, Jiangxi Province, China. Students were asked to complete questionnaires regarding family relationships, negative life events, and depressive symptoms. A mediation analysis was carried out using a multiple regression analysis and the PROCESS macro method. Of all participants, 19.9% reported experiencing depressive symptoms. The prevalence of depressive symptoms was 13.0% and 29.2% in participants with good and poor parental relationships, and the prevalence of depressive symptoms was 11.4% and 30.9% in participants with closed and alienated parental-child relationships, respectively. Parental relationships, parental-child relationships, and negative life events were positively correlated with depressive symptoms. The effect of parental relationships on depressive symptoms was fully mediated by negative life events (Effect = 0.052, 95% CI = [0.023, 0.082]), while the effect of parent-child relationships on adolescent depressive symptoms was partially mediated by negative life events (Effect = 0.075, 95% CI = [0.048, 0.104]). Our results showed a high prevalence of depressive symptoms in Chinese adolescents. Poor family relationships may have the potential to increase the risk of depressive symptoms, and they could affect depressive symptoms through negative life events.

Porcine blood polypeptide (PBP) has been reported to play roles in plant growth. However, its functions in alleviating salt stress in wheat remain unclear. The present study was conducted to investigate the physiological and biochemical mechanisms underlying the effects of PBP on wheat salt tolerance. Morphological analysis showed that PBP-primed seedlings exhibited improved growth performance, significantly greater biomass accumulation, and enhanced root system development. Physiological assessments showed that primed seedlings displayed higher values of Pn, Gs, Tr, Fv/Fm, Fv′/Fm′, ΦPSII, and NPQ, along with increased contents of total chlorophyll, Pro, TSS, and RWC. In addition, the activities of antioxidant enzymes, including SOD, CAT, POD, and APX, were significantly elevated, whereas the levels of H2O2, O2−, MDA, and REC were significantly reduced. PCA indicated that antioxidant enzyme activity, osmotic regulation, and ROS accumulation were the major factors associated with the PBP-mediated salt stress response. Furthermore, qRT-PCR analysis suggested that exogenous PBP might enhance wheat salt tolerance by coordinately modulating multiple molecular mechanisms. Taken together, this study broadens the potential applications of PBP by demonstrating its capacity to improve wheat salt tolerance.

Kindlin-1, -2, and -3 directly bind integrin β cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and links to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin β cytoplasmic tail as the integrin-binding pocket in the F3 subdomain of 1 protomer is occluded by the pleckstrin homology (PH) domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells reconstituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared with those reconstituted with wild-type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.