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Background: Chronic insomnia increases the risk of various health problems and mental illness. Existing research suggests promise for both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in treating chronic insomnia individually. However, the combined effects of tDCS and rTMS on this condition remain unclear. This study aimed to verify the efficacy and safety of tDCS combined with rTMS for the treatment of adult patients with chronic insomnia. Methods: This was a randomised double-blind parallel-group controlled study. Overall, 157 participants with chronic insomnia were randomly assigned to one of three neurotherapy regimens: tDCS + rTMS, sham tDCS + rTMS, or tDCS + sham rTMS. All groups received 20 treatment sessions over 4 consecutive weeks. The primary outcome was the change in patients' sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI) at 2 weeks, 4 weeks, and 3 months of follow-up. The secondary outcome was the assessment of different dimensions of depression and anxiety in patients through the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), as well as the occurrence of adverse events. Results: Throughout the intervention and after the 3-month follow-up, the tDCS + rTMS group had significantly reduced total PSQI scores compared with the other two groups [tDCS + rTMS, 9.21 vs. sham tDCS + rTMS, 10.03; difference − 1.10; 95% confidence interval (CI), − 1.82 to − 0.38; p = 0.003; tDCS + rTMS, 9.21 vs. tDCS + sham rTMS, 10.76; difference − 2.14; 95% CI, − 2.90 to − 1.38; p < 0.001; sham tDCS + rTMS, 10.03 vs. tDCS + sham rTMS, 10.76; difference − 1.04; 95% CI, − 1.82 to − 0.26; p = 0.010), indicating improved overall sleep quality. Total HAMD and insomnia factor scores were significantly lower in the tDCS + rTMS group than in the other two groups after treatment (p < 0.05). Notably, no adverse events or serious adverse reactions were observed during the study period. Conclusions: Combining tDCS with rTMS effectively relieved insomnia symptoms, achieving a significant therapeutic effect after 2-week of intervention, and demonstrating the persistence of treatment effects in later follow-up, emphasising the advantages of combination therapy in improving treatment stability and long-term benefits, reflecting the rapid and effective augmentation of combination therapy. This combined therapy may serve as a safe and effective treatment for adults with chronic insomnia. Trial registration: This study was registered as a clinical trial with the China Clinical Trial Registration Center (ChiCTR2100052681). [ABSTRACT FROM AUTHOR]

Gastric cancer remains a significant therapeutic challenge, highlighting the need for new strategies to improve treatment efficacy. This study investigates the potential of combined therapy with the novel Thiopyrano[2,3-d]Thiazole derivative LES-6400 and the anti-HER2 antibody trastuzumab in AGS gastric cancer cells. The antitumor effects of the combined therapy were evaluated using various techniques, including the MTT assay for cell viability, [3H]-thymidine incorporation for DNA synthesis, and flow cytometry to assess apoptosis (Annexin V-FITC/PI staining), mitochondrial membrane potential (MMP), and inflammatory cytokine levels. ELISA was employed to measure the levels of IL-6, p53, and cytochrome C. The combination of LES-6400 (1 µM) and trastuzumab (10 µg/mL) demonstrated superior antitumor activity compared to monotherapy with either agent in AGS gastric cancer cells. The combination therapy enhanced apoptosis, presumably by inducing oxidative stress in the cells and disrupting mitochondrial membrane potential. Additionally, a significant increase in p53 protein levels and modulation of interleukin levels, including a marked reduction in IL-6 levels, were observed, suggesting an impact on apoptotic and inflammatory responses. These findings indicate that the combined use of LES-6400 and trastuzumab is a promising therapeutic strategy for gastric cancer, warranting further investigation into the mechanisms of action and potential clinical applications of this combined approach. [ABSTRACT FROM AUTHOR]

Cancer is a disease affecting humans around the world. Exploring a deep understanding of the state/parameter estimation based on the drug prescription provides an awareness of the patient's experience during the treatment. Applying controllers to such systems with the primary aim of reducing cancer cells with the fewest side effects is a very interesting field in the past decade. The usual assumptions followed when designing a controller are that all system parameters are constant and all states are measurable. However, this is not the case in reality. In this article, based on a five-states differential equation model, which models a combined therapy of chemotherapy and anti-angiogenic, the state and/or parameters are estimated using an unscented Kalman filter while a nonlinear adaptive controller produces drug injection rate as the control signals utilizing the estimated state/parameter. The advantage of this estimation method is that, unlike in the traditional extended Kalman filter, nonlinear dynamics can be used without any linearization. The results show that the state and parameter estimation with UKF was successful. This idea can be used to assign a mathematical cancer dynamic for any individual, and state/parameter estimation can be studied and verified throughout a patient's treatment. [ABSTRACT FROM AUTHOR]

To determine the synergistic effect and mechanism of AO/854, a new Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, cell viability assays, neutral comet assays, and Western blotting (WB) were performed on prostate cancer (PCa) cells. According to our findings, combining AO/854 and CDDP enhanced the antiproliferative capabilities of PC3 cell lines. As evidenced by the upregulation of γH2AX, cleaved caspase-3/caspase-3, and BAX/Bcl-2, AO/854 dramatically increased PC3 apoptosis and DNA damage induced by CDDP. Furthermore, combining AO/854 and CDDP synergistically inhibited PC3 cell migration and invasion. In addition, AO/854 inhibited CDDP-induced S-phase cell-cycle arrest in PC3 cells while enhancing G2/M-phase cell-cycle arrest. In vivo, the antitumor efficacy of the combination therapy group was greater than that of the groups treated with AO/854 or CDDP alone. Our findings indicate that synergistic chemotherapy with AO/854 and CDDP may be a novel anticancer strategy for PCa. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate how the timing of transarterial chemoembolization (TACE) relative to systemic therapy (tyrosine-kinase inhibitors [TKIs] and immune checkpoint inhibitors [ICIs]) influences oncological outcomes in patients with hepatocellular carcinoma (HCC). A retrospective analysis was conducted on HCC patients treated with TACE plus TKIs and ICIs from January 2018 to February 2023. We compared objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between patients receiving TACE before versus after systemic therapies. Multivariate Cox regression analyses identified potential prognostic factors. Of the 194 patients enrolled, 111 received TACE before systemic therapies, and 83 after. The median age at diagnosis was 52.8 years. There were no significant differences in ORR (40.72% vs. 30.41%, p = 0.989) or DCR (48.45% vs. 35.57%, p = 0.770) between the groups. Likewise, OS (18.73 vs. 18.20 months, p = 0.091) and PFS (11.53 vs. 10.05 months, p = 0.336) were similar regardless of treatment sequence. In the result of Cox analysis, a 20% decrease in AFP from baseline at one month was associated with improved OS (HR = 0.35, 95% CI 0.17–0.70, p = 0.003) and PFS (HR = 0.69, 95% CI 0.49–0.96, p = 0.028). Large tumor size (≥ 10 cm) was a poor prognostic factor for OS (HR = 2.12, 95% CI 1.07–4.21, p = 0.032), and the presence of portal vein tumor thrombus adversely affected PFS (HR = 2.31, 95% CI 1.47–3.62, p < 0.001). The sequencing of TACE and systemic therapies does not significantly impact the prognosis of advanced HCC. A 20% reduction in AFP within one month of treatment commencement emerges as a protective prognostic factor for HCC. [ABSTRACT FROM AUTHOR]

ABSTRACT Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease‐modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease‐modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma.Trial Registration: clinicaltrials.gov identifier: NCT06027073 [ABSTRACT FROM AUTHOR]

• Combination therapy is efficacious in treating women with OAB. • Rapid effect and persistent clinical improvement were evident from week 2. • There were fewer side effects over time. We hypothesized that combination therapy would provide a synergistic effect to improve treatment outcomes for overactive bladder (OAB), thus enhancing the motivation for continuous exercise, and that it would be associated with fewer adverse events than monotherapy. Therefore, we investigated whether biofeedback-assisted pelvic floor muscle training (PFMT), drug therapy, or a combination of both would be more effective in improving the symptoms of OAB. This randomized controlled trial included women diagnosed with OAB. Group 1 received biofeedback-assisted pelvic muscle floor training (PFMT) for 12 weeks; group 2 took 5 mg of solifenacin/day for 12 weeks; and group 3 received 5 mg of solifenacin/day in combination with biofeedback-assisted PFMT during the first 4 weeks and biofeedback-assisted PFMT for another 8 weeks. All participants had 5 follow-up visits. The primary outcomes were objective improvement of OAB symptoms and quality of life. The secondary outcomes were treatment-related adverse events, subjective improvement of OAB symptoms, and electromyographic activity of pelvic floor muscle (PFM) contraction. All participants reported significant improvement of OAB symptoms and quality of life. Participants in group 2 experienced more pronounced adverse events than those in group 3. Intervention duration was positively associated with subjective improvement in OAB symptoms in groups 2 and 3. Drug-related adverse events, including dry mouth, myalgia, and restlessness, had a negative impact on the subjective improvement of OAB symptoms in group 2. In group 1, exercise adherence was positively correlated with subjective improvement of OAB symptoms, whereas in group 3, PFM contraction and biofeedback effect were positively correlated with symptom improvement. Combination therapy is efficacious in treating women with OAB. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each. Ferroptosis in the tumor microenvironment involves intricate crosstalk between tumor cells and immune cells. Through MHC recognition, CD8+T cells activate the JAK1/STAT1 pathway in tumor cells, impairing the function of System Xc and reducing GSH and GPX4 expression to promote tumor cell ferroptosis. Additionally, activation of the STAT1-IRF1-ACSL4 pathway could also promote ferroptosis. The blockade of the antioxidant pathway in tumor cells induces ferroptosis, and the released DAMPs could promote DCs maturation through the cGAMP-STING-TBK1 pathway, leading to antigen presentation that activates CD8+T cells. The release of DAMPs also induces the M1-type polarization of macrophages, which exerts an anti-tumor effect. The anti-tumor effects of CD8+T cells could also be enhanced by blocking inhibitory immune checkpoints such as PD-1, PD-L1, CTLA4, and LAG3. Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; BH4, tetrahydrobiopterin; cGAMP, cyclic GMP-AMP; CTLA4, cytotoxic T lymphocyte-associated antigen-4; DCs, dendritic cells; DHFR, dihydrofolate reductase; DHODH, dihydroorotate dehydrogenase; GPX4, glutathione peroxidase 4; GSH, glutathione; HIF-1α, Hypoxia-Inducible Factor-1α;IFN-γ, interferon-γ; IRF1, interferon regulatory factor 1;IRP1, iron regulatory protein 1; JAK 1, janus kinase; LAG3, lymphocyte activation gene 3; MHC, major histocompatibility complex; NRF2, nuclear factor erythroid-2-related factor 2; PD-1, programmed death protein -1; PD-L1, programmed death ligand 1; PUFA, polyunsaturated fatty acid; ROS, reative oxygen species; STAT1, signal transducer and activator of transcription 1; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1 TLR2, toll-like receptor 2. This diagram was drawn by Figdraw (www.figdraw.com). [ABSTRACT FROM AUTHOR]

Purpose: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer. Methods: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan–Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response. Results: We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023). Conclusion: In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits. [ABSTRACT FROM AUTHOR]

Background: Retroperitoneal liposarcoma (RLPS) typically shows limited response to standard chemotherapy, presenting a challenge in treating advanced or metastatic RLPS. Objective: This study aimed to evaluate the potential advantages of a combined therapeutic strategy utilizing eribulin, anlotinib, and camrelizumab. Design: Between December 2020 and March 2023, this retrospective study enrolled patients with advanced or metastatic RLPS who received treatment at Peking University Cancer Hospital Sarcoma Center. The treatment regimen involved eribulin plus anlotinib and camrelizumab administered every 3 weeks (Q3W). Methods: Efficacy was assessed following the Response Evaluation Criteria in Solid Tumors version 1.1, while safety was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Results: The study included 47 patients with RLPS with a median age of 55.5 years. Patients received a median of 4.5 (range, 2–21) cycles of treatment. Notably, partial response was observed in 8 patients (18.2%), while 25 (56.8%) exhibited stable disease. The objective response rate (ORR) and disease control rate were 18.2% and 75%, respectively. Significant differences in ORR were observed among histological subtypes (well-differentiated vs de-differentiated vs myxoid: 0 vs 17.9% vs 50%; p = 0.039). Six patients underwent surgery before disease progression, and one patient with myxoid liposarcoma (MLPS) had a pathological complete response. With a median follow-up of 21.8 (range, 2.7–30.7) months, the median progression-free survival (mPFS) was 6.9 (95% confidence interval (CI), 4.7–9.1) months, and the 6-month PFS rate was 60.5%. Based on various histological subtypes, the mPFS was 8.4 (95% CI, 4.1–12.7) months with well-differentiated liposarcoma, 5.8 (95% CI, 3.3–8.3) months with de-differentiated liposarcoma and not reached with MLPS, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 36 (76.6%) patients, with grade 3 or higher TRAEs in 21 (44.7%) patients. The most common TRAEs were neutropenia (53.2%), proteinuria (21.3%), and anorexia (21.3%). Conclusion: The combined treatment strategy involving eribulin, anlotinib, and camrelizumab showed promising efficacy and manageable safety in patients with advanced or metastatic RLPS, particularly in those with MLPS. [ABSTRACT FROM AUTHOR]

Prodrug nanoparticles have been explored as an effective means for drug delivery because of controlled drug release in a stimulus-responsive manner. Organellar-targeted drug delivery could enhance the efficacy of cancer therapy. Herein, pH and light dual responsive mitochondrial targeted prodrug nanoparticles were designed to deliver both chemotherapeutic drugs and photosensitisers for enhanced antitumour efficacy. The prodrug nanoparticles (TPP-PEI-PheoA/ALG=DOX NPs, TPPAD NPs) are composed of a light-responsive mitochondrial targeted prodrug (triphenylphosphonium and pheophorbide A modified polyethyleneimine, TPP-PEI-PheoA) and a pH-responsive prodrug (doxorubicin conjugated alginate with Schiff's base bond, ALG=DOX). TPPAD NPs were prepared through electrostatic interaction. TPPAD NPs could simultaneously deliver DOX and PheoA to the tumour site by passive targeting effect, release drugs in a designed mode and deliver drugs to the target organelles. Moreover, TPPAD NP-based PDT could induce immunogenic cell death of tumour cells, thereby activating the immune system. TPPAD NPs greatly enhanced antitumour efficacy by combinational therapy. Taken together, this prodrug nanoparticle platform has appeared to be a simple and smart nanomedicine for targeted tumour combinational treatment. [ABSTRACT FROM AUTHOR]

Metastatic cancers are responsible for 90% of cancer related deaths and melanoma is known as one of the deadliest cancers. Dacarbazine (DTIC) for metastatic melanoma has become an approved first-line treatment in routine clinical practice. However, response rates to single-drug therapy with dacarbazine are quite low. Therefore, combination drug therapy as a method of treatment that combines two or more therapeutic agents is the cornerstone of cancer therapy. Here, we examined the effects of the combination of ornidazole, a derivative of 5-nitroimidazole which is active against protozoa and anaerobic bacteria, and DTIC on melanoma cells to investigate novel advanced combination therapies for melanoma. Doses in this study are 0, 800 and 1200µg/mL for ornidazole, 0, 5, 25, 50, 100, 200, 300, 600, 1200μM/L for DTIC and 800µg/mL+100μM/L, 800µg/mL+200μM/L, 1200µg/mL+100μM/L, 1200µg/mL+200μM/L for ornidazole+DTIC combination. Treatment effect of ornidazole and DTIC as a single-agents and in combination on cell viability was investigated with crystal violet and MTT assays. As well as the effect of them on migration ability was assessed by wound healing assay, the effect of them on DNA damage induction was evaluated by comet assay in B16F10 melanoma cells in vitro. Our data showed that combination treatment with ornidazole and DTIC markedly inhibited cancer cell proliferation and migration. DNA damage was also significantly induced by this combination treatment. Our study showed that ornidazole/DTIC combination drug therapy has more effective therapeutic potential for melanoma compared to DTIC therapy alone. In conclusion, our findings suggest that combination therapy with ornidazole/ DTIC could serve as a new and valuable approach for melanoma treatment. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains one of the most lethal malignancies due to its aggressive nature and resistance to conventional therapies. This study investigates the anti-proliferative, pro-apoptotic, and anti-migratory effects of Gemcitabine (GC) and Withaferin A (WFA) on pancreatic cancer cell lines PANC-1 and Hs766t. The MTS assay revealed that both compounds effectively inhibit cell proliferation, with WFA showing a stronger effect in Hs766t cells. Flow cytometry analysis demonstrated that GC and WFA, particularly in combination, significantly induce apoptosis in both cell lines. Migration assays confirmed the potent inhibition of cell migration by both compounds, with the combination treatment being the most effective. Furthermore, actin cytoskeleton analysis indicated substantial changes in cell morphology and stiffness, suggesting that GC and WFA disrupt the structural integrity of cancer cells. Additionally, the study highlights a ROS-mediated mechanism underlying the effects of GC and WFA, as evidenced by increased ROS levels following treatment, which were attenuated by N-acetylcysteine. Importantly, NF-κB activity was significantly modulated, with WFA reducing NF-κB activation induced by GC, potentially contributing to the synergistic pro-apoptotic effect of the combination. These findings suggest that the combination of GC and WFA may offer a synergistic therapeutic approach for treating pancreatic cancer by targeting multiple aspects of tumor cell behavior. [ABSTRACT FROM AUTHOR]

Introduction: Posterior uveitis is a challenging intraocular inflammation that can lead to significant visual impairment if untreated. Understanding its clinical course and treatment outcomes is crucial for effective management. This study aimed to evaluate the demographic, clinical, and ocular characteristics of patients with posterior uveitis, determine visual outcomes post-treatment, assess the effectiveness of various treatment modalities, and identify factors influencing visual outcomes. Materials and Methods: A retrospective observational analysis was conducted on 104 patients diagnosed with posterior uveitis at a tertiary care hospital. Data collected included demographic details, clinical characteristics, treatment modalities, and visual outcomes. Statistical analyses were performed to assess associations and treatment effectiveness. Results: The majority of patients were aged 20-40 years (43.3%) and predominantly male (59.6%). Most cases were unilateral (60.6%), with varied symptom durations and associations with systemic diseases. Systemic corticosteroids (62.5%) were the most common treatment, followed by immunosuppressive agents (43.3%). Visual acuity improved in 65.4% of patients post-treatment, with combined therapy showing the highest mean improvement (0.30 logMAR). Conclusion: This study provides insights into the management and prognosis of posterior uveitis, highlighting the efficacy of systemic corticosteroids and combined therapies in improving visual outcomes. Factors such as age, gender, symptom duration, and systemic diseases significantly influence treatment outcomes. Early diagnosis and tailored treatment strategies are crucial for optimizing visual outcomes in posterior uveitis patients. [ABSTRACT FROM AUTHOR]

Abstract To determine the synergistic effect and mechanism of AO/854, a new Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, cell viability assays, neutral comet assays, and Western blotting (WB) were performed on prostate cancer (PCa) cells. According to our findings, combining AO/854 and CDDP enhanced the antiproliferative capabilities of PC3 cell lines. As evidenced by the upregulation of γH2AX, cleaved caspase-3/caspase-3, and BAX/Bcl-2, AO/854 dramatically increased PC3 apoptosis and DNA damage induced by CDDP. Furthermore, combining AO/854 and CDDP synergistically inhibited PC3 cell migration and invasion. In addition, AO/854 inhibited CDDP-induced S-phase cell-cycle arrest in PC3 cells while enhancing G2/M-phase cell-cycle arrest. In vivo, the antitumor efficacy of the combination therapy group was greater than that of the groups treated with AO/854 or CDDP alone. Our findings indicate that synergistic chemotherapy with AO/854 and CDDP may be a novel anticancer strategy for PCa.

Abstract Background Schizophrenia (SCZ) shares high clinical relevance with the immune system, and the potential interactions of psychopharmacological drugs with the immune system are still an overlooked area. Here, we aimed to identify whether the second-generation antipsychotics (SGA) monotherapy or combined therapy of SGA with other psychiatric medications influence the routine blood immunity biomarkers of patients with SCZ. Methods Medical records of inpatients with SCZ from January 2019 to June 2023 were retrospectively screened from June 2023 to August 2023. The demographic data and peripheral levels of cytokines (IL-2, IL-4, IL-6, TNF-α, INF-γ, and IL-17 A), lymphocyte subtype proportions (CD3+, CD4+, CD8 + T-cell, and natural killer (NK) cells), and thyroid autoimmune antibodies (thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb)) were collected and analyzed. Results 30 drug-naïve patients, 64 SGA monotherapy (20 for first-episode SCZ, 44 for recurrent SCZ) for at least one week, 39 combined therapies for recurrent SCZ (18 with antidepressant, 10 with benzodiazepine, and 11 with mood stabilizer) for at least two weeks, and 23 used to receive SGA monotherapy (had withdrawn for at least two weeks) were included despite specific medication. No difference in cytokines was found between the SGA monotherapy sub-groups (p > 0.05). Of note, SGA monotherapy appeared to induce a down-regulation of IFN-γ in both first (mean [95% confidence interval]: 1.08 [0.14–2.01] vs. 4.60 [2.11–7.08], p = 0.020) and recurrent (1.88 [0.71–3.05] vs. 4.60 [2.11–7.08], p = 0.027) episodes compared to drug-naïve patients. However, the lymphocyte proportions and thyroid autoimmune antibodies remained unchanged after at least two weeks of SGA monotherapy (p > 0.05). In combined therapy groups, results mainly resembled the SGA monotherapy for recurrent SCZ (p > 0.05). Conclusion The study demonstrated that SGA monotherapy possibly achieved its comfort role via modulating IFN-γ, and SGA combined therapy showed an overall resemblance to monotherapy.

PURPOSE: To evaluate the efficacy of combination therapy using transarterial chemoembolization with microwave ablation (MWA) therapy vs. MWA monotherapy for hepatocellular carcinomas (HCCs) >3 cm in size. METHODS: This two-arm retrospective observational study included patients with HCCs >3 cm who underwent either combination therapy (29 patients) or MWA monotherapy (35 patients) between 2014 and 2020. The treatment outcomes related to primary treatment efficacy, local tumor progression (LTP), tumor control rate, and overall survival were compared between each cohort. RESULTS: The technical success and primary efficacy were 96.56% and 100.00% in the combination therapy cohort, and 91.42% and 100.00% in the MWA cohort, respectively, over a mean follow-up period of 27.6 months. The 1- and 3-year rates of LTP-free survival were 78.57% and 69.56% in the combination therapy cohort, vs. 72.45% and 35.44% in the MWA cohort, respectively (P = 0.001). The overall progression-free survival was longer in the combination therapy cohort compared with the MWA cohort (median: 56.0 vs. 13.0 months; P = 0.017). With the incorporation of additional locoregional therapy, the overall survival rates were not significantly different, with 1- and 3-year overall survival rates of 100.00% and 88.71% in the combination therapy cohort and rates of 90.15% and 82.76% in the MWA cohort, respectively (P = 0.235). CONCLUSION: The combination therapy provided significantly longer upfront LTP-free survival in HCCs >3 cm when compared with the MWA treatment alone, albeit with similar local tumor control and overall survival rates when accounting for additional locoregional therapies.

Abstract Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

Chimeric antigen receptor (CAR‐T) cell therapy is a newly developed immunotherapy strategy and has achieved satisfactory outcomes in the treatment of hematological malignancies. However, some adverse effects related to CAR‐T cell therapy have to be resolved before it is widely used in clinics as a cancer treatment. Furthermore, the application of CAR‐T cell therapy in the treatment of solid tumors has been hampered by numerous limitations. Therefore, it is essential to explore novel strategies to improve the therapeutic effect of CAR‐T cell therapy. In this review, we summarized the recently developed strategies aimed at optimizing the generation of CAR‐T cells and improving the anti‐tumor efficiency of CAR‐T cell therapy. Furthermore, the discovery of new targets for CAR‐T cell therapy and the combined treatment strategies of CAR‐T cell therapy with chemotherapy, radiotherapy, cancer vaccines and nanomaterials are highlighted.

Abstract This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1–3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6–17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413–575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138–401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.

Background: This study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Methods: A dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan–Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied. Results: A prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC. Conclusions: AC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC. [ABSTRACT FROM AUTHOR]

This study investigated the potential of immune checkpoint inhibitors (ICIs) combined with chemotherapy as a promising treatment approach for malignancies. This report focuses on a patient with drug-induced liver injury (DILI) following the administration of chemotherapy and ICIs. A 63-year-old patient with non-small cell lung adenocarcinoma (NSCLC) initially underwent γ-knife treatment and subsequently received a combination of chemotherapy comprising bevacizumab and camrelizumab. Due to liver abnormalities, both chemotherapy and ICIs were stopped on day 21. The patient's liver function improved within a month after methylprednisolone treatment. Subsequently, the patient received carboplatin, pemetrexed, and bevacizumab without complications. This finding supported the notion that DILI was likely triggered by the ICI. This case series details a complex instance of DILI resulting from the use of ICIs and pemetrexed/carboplatin. The alignment of the pathological findings and clinical presentation strongly suggested ICI-induced DILI, which was further supported by the definitive response to steroid treatment. This information is important for clinicians, as it emphasizes the importance of closely monitoring liver function and being aware of potential adverse effects associated with ICIs. Such insights contribute to more effective patient care. [ABSTRACT FROM AUTHOR]

Combinations of Chinese patent medicines (CPM) with antidepressants (including selective serotonin reuptake inhibitors (SSRI), selective serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and noradrenergic and specific serotonergic antidepressants (NaSSA)) are frequently utilized for treating depression in adults. However, the efficacy and safety of these combination treatments remain to be established. Systematic search was conducted in seven electronic databases, regulatory websites and international registers of trials from 1994 to 2023 that included adult patients with depressive disorders who received CPM combined with antidepressants. The Multiple-Treatment Meta-Analysis (MTMA) was conducted using a random effects model with Stata/MP17 and R4.3.5 software. Primary outcomes were total efficacy rate, Hamilton Depression Scale (HAMD) score, and Treatment Emergency Symptom Scale (TESS) score. Secondary outcomes included brain-derived neurotrophic factor (BDNF) levels. A total of 146 randomized controlled trials (13,754 participants: 6929 in intervention and 6825 in control groups) were included. For total effective rate, Multiple-Treatment Meta-Analysis results showed that the overall effect of combined intervention was better compared with antidepressants alone, where Jieyuanshenkeli (JYASKL) presented the optimal option for improving total efficacy (OR = 5.39, 95% CI [2.60, 11.18], SUCRA = 84.50%). In reduding the HAMD, Shuganjieyujiaonang (SGJYJN) was most likely to reduce the HAMD score (SMD = −2.20, 95% CI [-3.06, −1.33], SUCRA = 86.10%), Jieyuanshenkeli (JYASKL),Tianewangbuxindan (TWBXD), Shuyukeli (SYKL), Anshenbuxinwan (ASBXW) combination intervention did not appear to be statistically superior to antidepressants alone. In theTreatment Emergency Symptom Scale (TESS), Wulinjiaonang induced the most significant reduction in TESS score (SMD = −1.98, 95% CI [-3.59, −0.36], SUCRA = 90.40%). Tianmengjiaonang (TMJN) + Antidepressants(AD) (SUCRA = 88.30%) displayed the highest scores in increasing the levels of BDNF, although not statistically significant compared to Antidepressants(AD) alone (SMD = 1.23, 95% CI [0.90, 1.55]). Combinations of CPM and antidepressants showed superior efficacy over antidepressants alone. The optimal combinations were determined as Shuganjieyu Jiaonang (SGJYJN)/SSRIs and Jieyuanshenkeli (JYASKL)/SSRIs. In terms of safety, results showed that combination therapy did not show better TESS efficacy than antidepressants alone.Although some of the combination interventions were not superior than antidepressants alone in reducing HAMD scores,our findings provide a potentially significant alternative option for clinical complementary therapy. However, these results require further validation through larger sample sizes, multicenter randomized controlled trials, and real-world data. [ABSTRACT FROM AUTHOR]

Immunocompromised patients with impaired humoral immunity are at risk for persistent COVID-19 (pCOVID), a protracted symptomatic disease with active viral replication. To establish a national consensus statement on the diagnosis, treatment, management, isolation, and prevention of pCOVID in adults. We base our suggestions on the available literature, our own experience, and clinical reasoning. Literature on the treatment of pCOVID is scarce and consists of few case reports and case series. The available studies provide low-quality evidence for monoclonal antibodies, convalescent plasma, antiviral drugs, and immunomodulators. Different combination therapies are described. Continuous viral replication and antiviral treatment may lead to the development of mutations that confer resistance to therapy. To reduce the risk of resistance and improve outcomes, we suggest treating pCOVID with a combination of antibody-based therapy and two antiviral drugs for duration of 5–10 days. Immunomodulatory therapy can be added in patients with an inflammatory clinical picture. In cases of treatment failure or relapse, prolonged antiviral treatment can be considered. For the prevention of pCOVID, we suggest active and passive vaccination and early initiation of treatment for acute COVID-19. Additional research on pCOVID treatment is urgently needed. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR‐T) cell therapy is a newly developed immunotherapy strategy and has achieved satisfactory outcomes in the treatment of hematological malignancies. However, some adverse effects related to CAR‐T cell therapy have to be resolved before it is widely used in clinics as a cancer treatment. Furthermore, the application of CAR‐T cell therapy in the treatment of solid tumors has been hampered by numerous limitations. Therefore, it is essential to explore novel strategies to improve the therapeutic effect of CAR‐T cell therapy. In this review, we summarized the recently developed strategies aimed at optimizing the generation of CAR‐T cells and improving the anti‐tumor efficiency of CAR‐T cell therapy. Furthermore, the discovery of new targets for CAR‐T cell therapy and the combined treatment strategies of CAR‐T cell therapy with chemotherapy, radiotherapy, cancer vaccines and nanomaterials are highlighted. [ABSTRACT FROM AUTHOR]

Copyright of Istanbul Gelisim University Journal of Health Sciences / İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi is the property of Istanbul Gelisim Universitesi Saglik Bilimleri Yuksekokulu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Materiae Compositae Sinica is the property of Acta Materiea Compositae Sinica Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The mitogen‐activated protein kinase (MAPK) extracellular signal‐regulated kinase 5 (ERK5) is emerging as a promising target in cancer. Indeed, alterations of the MEK5/ERK5 pathway are present in many types of cancer, including melanoma. One of the key events in MAPK signalling is MAPK nuclear translocation and its subsequent regulation of gene expression. Likewise, the effects of ERK5 in supporting cancer cell proliferation have been linked to its nuclear localization. Despite many processes regulating ERK5 nuclear translocation having been determined, the nuclear transporters involved have not yet been identified. Here, we investigated the role of importin subunit alpha (α importin) and importin subunit beta‐1 (importin β1) in ERK5 nuclear shuttling to identify additional targets for cancer treatment. Either importin β1 knockdown or the α/β1 importin inhibitor ivermectin reduced the nuclear amount of overexpressed and endogenous ERK5 in HEK293T and A375 melanoma cells, respectively. These results were confirmed in single‐molecule microscopy in HeLa cells. Moreover, immunofluorescence analysis showed that ivermectin impairs epidermal growth factor (EGF)‐induced ERK5 nuclear shuttling in HeLa cells. Both co‐immunoprecipitation experiments and proximity ligation assay provided evidence that ERK5 and importin β1 interact and that this interaction is further induced by EGF administration and prevented by ivermectin treatment. The combination of ivermectin and the ERK5 inhibitor AX15836 synergistically reduced cell viability and colony formation ability in A375 and HeLa cells and was more effective than single treatments in preventing the growth of A375 and HeLa spheroids. The increased reduction of cell viability upon the same combination was also observed in patient‐derived metastatic melanoma cells. The combination of ivermectin and ERK5 inhibitors other than AX15836 provided similar effects on cell viability. The identification of importin β1 as the nuclear transporter of ERK5 may be exploited for additional ERK5‐inhibiting strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors. [ABSTRACT FROM AUTHOR]

Enzyme‐based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico‐chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off‐target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine‐based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug‐integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseTherapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cancer remains a significant global challenge, with escalating incidence rates and a substantial burden on healthcare systems worldwide. Herein, we present an in-depth exploration of the intricate interplay between cancer cell death pathways and tumor immunity within the tumor microenvironment (TME). We begin by elucidating the epidemiological landscape of cancer, highlighting its pervasive impact on premature mortality and the pronounced burden in regions such as Asia and Africa. Our analysis centers on the pivotal concept of immunogenic cell death (ICD), whereby cancer cells succumbing to specific stimuli undergo a transformation that elicits robust anti-tumor immune responses. We scrutinize the mechanisms underpinning ICD induction, emphasizing the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) as key triggers for dendritic cell (DC) activation and subsequent T cell priming. Moreover, we explore the contributions of non-apoptotic RCD pathways, including necroptosis, ferroptosis, and pyroptosis, to tumor immunity within the TME. Emerging evidence suggests that these alternative cell death modalities possess immunogenic properties and can synergize with conventional treatments to bolster anti-tumor immune responses. Furthermore, we discuss the therapeutic implications of targeting the TME for cancer treatment, highlighting strategies to harness immunogenic cell death and manipulate non-apoptotic cell death pathways for therapeutic benefit. By elucidating the intricate crosstalk between cancer cell death and immune modulation within the TME, this review aims to pave the way for the development of novel cancer therapies that exploit the interplay between cell death mechanisms and tumor immunity and overcome Challenges in the Development and implementation of Novel Therapies. [ABSTRACT FROM AUTHOR]

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1–3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6–17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413–575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138–401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature. [ABSTRACT FROM AUTHOR]

Background: Lung tumors are prevalent malignancies associated with a high mortality rate, imposing significant medical and societal burdens. Although immunotherapy shows promise in improving survival, response rates are relatively modest. Thermal ablation can not only eliminate tumor cells directly but also enhance antitumor immunity response, thus manifesting a remarkable propensity to synergize with immunotherapy. Summary: In this review, we provided a brief overview of the application of thermal ablation in peripheral lung tumors. We summarized the patient selection of thermal ablation. We highlighted the potential of thermal ablation to augment the antitumor immune response, offering a promising avenue for combined therapies. We summarized studies assessing the synergistic effects of thermal ablation and immunotherapy in preclinical and clinical settings. Lastly, we underscored the urgent issues that warrant in-depth exploration when applying thermal ablation and immunotherapy to lung tumor patients. Key Messages: This review emphasized the prospects of using thermal ablation combined with immunotherapy in patients with peripheral lung tumors. However, further research is needed to enhance and optimize this treatment strategy. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption–desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m−2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation. [ABSTRACT FROM AUTHOR]

Combination therapies can enhance the sensitivity of cancer to drugs, lower drug doses, and reduce side effects in cancer treatment. However, differences in the physicochemical properties and pharmacokinetics of different therapeutic agents limit their application. To avoid the above dilemma and achieve accurate control of the synergetic ratio, a nanoscale co-delivery system (NCDS) has emerged as a prospective tool for combined therapy in cancer treatment, which is increasingly being used to co-load different therapeutic agents. In this study, we have summarized the mechanisms of therapeutic agents in combination for cancer therapy, nanoscale carriers for co-delivery, drug-loading strategies, and controlled/targeted co-delivery systems, aiming to give a general picture of these powerful approaches for future NCDS research studies. [ABSTRACT FROM AUTHOR]

The incidence of primary liver cancer (PLC) has experienced a significant global increase, primarily attributed to the rise in hepatocellular carcinoma (HCC). Unfortunately, HCC is often diagnosed in advanced stages, leaving patients with limited treatment options. Therefore, transformation therapy is a crucial approach for long-term survival and radical resection in patients with advanced HCC. Conversion therapy has demonstrated promise in the treatment of advanced HCC. When integrated with the FOLFOX regimen, hepatic artery infusion chemotherapy (HAIC) can significantly improve tumor response efficiency, leading to high conversion and resection rates. We reviewed landmark trials of HAIC in combination with different drugs or means for the treatment of HCC to determine the clinical value of HAIC-centric translational therapies in HCC treatment. Furthermore, we specifically emphasize the advantages associated with employing FOLFOX-HAIC in the treatment of advanced HCC. The combination of HAIC with the FOLFOX regimen can help prevent the low intratumoral accumulation and high adverse reaction rate caused by the FOLFOX alone, holding significant potential in the comprehensive treatment of future HCC patients. [ABSTRACT FROM AUTHOR]

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies.

Photodynamic therapy (PDT), as one of the most promising cancer therapy methods, is still limited by several drawbacks, such as tissue hypoxia and shallow light penetration of blue-violet light (200–450 nm), and red light (750 nm) is more penetrating to tissues than blue-violet light, but still lower than near-red light (750–1350 nm). Therefore, we proposed a synergistic therapy system by combining the near-infrared light-triggered PDT with nitric oxide (NO)-based gas therapy to enhance the anti-tumor effects. Upconversion nanoparticles (UCNPs) were loaded with the photosensitizers of ZnPc and the NO donors of l-arginine (L-Arg) to obtain the nanocomposites of UCN@mSiO2@ZnPc@L-Arg. Under 980 nm laser irradiation, reactive oxygen species (ROS) could be produced for PDT and react with l-Arg to produce NO, which is previously reported to have a greater killing effect on tumor cells than ROS and also plays an important role in promoting PDT in our study. Both the in vitro and in vivo tests demonstrated that the combined therapy of PDT with NO therapy could enhance the tumor killing effect significantly compared with the unique application of PDT. The UCNPs-based nanocomposites are expected to be widely used in biomedicine for tumor inhibition.

Jingjing Wei,1 Chunhong Zhang,1 Yi Leng,1 Mingming Li,1 Lingyun Du,1 Zhiqiang Cao,2 Xia Zhu,1 Changyu Han,1 Liya Meng1 1Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Liya Meng, Department of Dermato-venereology, The Second Hospital of Shandong University, 247 Beiyuan Dajie Street, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email mly0706@sina.comObjective and Design: The treatment of recurrent rosacea has always been a problem. Oral minocycline has been widely used in the treatment of rosacea. However, the efficacy and safety of ozonated hydrotherapy combined with LED yellow light irradiation and oral minocycline for mild to moderate papulopustular rosacea (PPR) has not been thoroughly studied.Methods: Patients with rosacea who met the criteria and had complete clinical statistic admitted to our hospital from April 2021 to September 2022 were retrospectively collected and divided into combined therapy group and oral only group. The patients in the two groups were treated with minocycline for 8 weeks. In addition, the patients in combined therapy group were treated with ozone hydrotherapy once a week, followed by LED yellow light irradiation for a total of 4 weeks. The Investigator’ s global assessment (IGA) score was used to assess the condition. The efficacy was evaluated using the patients’ subjective symptom scores. Skin lesion images and adverse reactions were recorded. The recurrence rate was observed after 24 weeks of follow-up.Results: A total of 39 patients included in the study. After 4 weeks of treatment, the effective rate was 90% in combined therapy group and 52.63% in oral only group (p< 0.05). After 8 weeks of treatment, the total score of the patients’ subjective symptom scores and the scores of itching and burning sensation in combined therapy group were lower than those in oral only group (p< 0.05). After 24 weeks of follow-up, the recurrence rate of combined therapy group was 5%, and that of oral only group was 26.32%. The mild adverse reactions experienced by both groups disappeared during follow-up.Conclusion: This combination therapy has a significant, rapid and safe therapeutic effect, especially in relieving itching and burning sensations, and may reduce the recurrence rate.Keywords: papulopustular rosacea, ozonated hydrotherapy, LED yellow light, minocycline, combined therapy

Glioblastoma (GBM) is one of the most aggressive and hard to treat cancers. Traditional anti-cancer treatment methods have low efficiency and the lifespan after diagnosis is only 12–18 months. Brain tumor cells overexpress many proteins that play an important role in tumor progression and can be used as therapeutic targets. One of the promising approaches in cancer treatment is down-regulation of an extracellular matrix glycoprotein – Tenascin-C (TN-C) through RNA interference therapy. However, the effective delivery of double stranded RNA with one strand complementary to TN-C mRNA sequence is difficult due to rapid degradation by nucleases and low intracellular uptake. Polydopamine (PDA), a biomimetic polymer characterized by high biocompatibility and simple modification ability, is commonly used in nanobiomedicine to create a drug/gene delivery vehicle. Furthermore, photothermal characteristics of this polymer enable its application in photothermal therapy (PTT), which is a great option for cancer treatment. Here we synthesize PDA nanoparticles (NPs) coated with polyamidoamine dendrimers generation 3.0 (DD3.0) for therapeutic anti-TN-C RNA and doxorubicin delivery. As prepared PDA@DD3.0 NPs are then used in combined drug delivery, gene silencing, and PTT of GBM. The obtained materials are analyzed in terms of physicochemical and photothermal properties as well as their cytotoxicity, using human GBM cells. The results demonstrate that the obtained nanocarriers are effective non-viral vehicle for combined therapeutic approach for killing glioma cells via anti-TN-C RNA delivery and combined chemo-PTT therapy (CT-PTT). The application of PDA@DD3.0 NPs contributed to the 3-fold reduction in the proliferation rate of GBM cells, a decrease in the level of TN-C expression (by 30%) and a reduction in the number of viable cells by up to 20%.

Introduction: Compared to other cancer immunotherapies, oncolytic viruses possess several advantages, including high killing efficiency, excellent targeting capabilities, minimal adverse reactions, and multiple pathways for tumor destruction. However, the efficacy of oncolytic viruses as a monotherapy often falls short of expectations. Consequently, combining oncolytic viruses with traditional treatments to achieve synergistic effects has emerged as a promising direction for the development of oncolytic virus therapies. Methods: This article provides a comprehensive review of the current progress in preclinical and clinical trials exploring the combination therapies involving oncolytic viruses. Results: Specifically, we discuss the combination of oncolytic viruses with immune checkpoint inhibitors, chemotherapy, targeted therapy, and cellular therapy. Discussion: The aim of this review is to offer valuable insights and references for the further advancement of these combination strategies in clinical applications. Further research is necessary to refine the design of combination therapies and explore novel strategies to maximize the therapeutic benefits offered by oncolytic viruses. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) has attracted significant attention in recent years as it is an innovative approach to tumor treatment. It involves the utilization of sound waves or ultrasound (US) to activate acoustic sensitizers, enabling targeted drug release for precise tumor treatment. This review aims to provide a comprehensive overview of SDT, encompassing its underlying principles and therapeutic mechanisms, the applications of nanomaterials, and potential synergies with combination therapies. The review begins by introducing the fundamental principle of SDT and delving into the intricate mechanisms through which it facilitates tumor treatment. A detailed analysis is presented, outlining how SDT effectively destroys tumor cells by modulating drug release mechanisms. Subsequently, this review explores the diverse range of nanomaterials utilized in SDT applications and highlights their specific contributions to enhancing treatment outcomes. Furthermore, the potential to combine SDT with other therapeutic modalities such as photothermal therapy (PTT) and chemotherapy is discussed. These combined approaches aim to synergistically improve therapeutic efficacy while mitigating side effects. In conclusion, SDT emerges as a promising frontier in tumor treatment that offers personalized and effective treatment options with the potential to revolutionize patient care. As research progresses, SDT is poised to play a pivotal role in shaping the future landscape of oncology by providing patients with a broader spectrum of efficacious and tailored treatment options. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, favorable outcomes have been reported for hepatocellular carcinoma treated with transarterial chemoembolization (TACE) combined with lenvatinib (LEN-TACE). However, the optimal treatment protocol remains unclear. In this study, we performed a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE). The objective was to assess changes in tumor hemodynamics following the 4-day lenvatinib administration and to evaluate the outcomes of this combined therapy. A significant decrease in intra-tumor flow after lenvatinib was observed, with a 100% technical success rate and no severe adverse events. Complete response rates (CR) at 1 month were 75%, and the 12-month progression-free survival (PFS) rate was 75.0%. The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction radio by lenvatinib prior to TACE (r = −0.55). The short-term LEN-TACE is feasible and safe, demonstrating promising results, including a high CR rate and prolonged PFS. Aim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4–12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = −0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory. [ABSTRACT FROM AUTHOR]

Aims The purpose was to evaluate the antimicrobial activity of highly soluble polypyrrole (Hs-PPy), alone or combined with oxacillin, as well as its antibiofilm potential against methicillin-resistant Staphylococcus aureus strains. Furthermore, the in silico inhibitory mechanism in efflux pumps was also investigated. Methods and results Ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and two reference strains were used. Antimicrobial activity was determined by broth microdilution, and the combination effect with oxacillin was evaluated by the checkerboard assay. The biofilm formation capacity of MRSA and the interference of Hs-PPy were evaluated. The inhibitory action of Hs-PPy on the efflux pump was evaluated in silico through molecular docking. Hs-PPy showed activity against the isolates, with inhibitory action between 62.5 and 125 µg ml−1 and bactericidal action at 62.5 µg ml−1, as well as synergism in association with oxacillin. The isolates ranged from moderate to strong biofilm producers, and Hs-PPy interfered with the formation of this structure, but not with mature biofilm. There was no in silico interaction with the efflux protein EmrD, the closest homolog to NorA. Conclusions Hs-PPy interferes with biofilm formation by MRSA, has synergistic potential, and is an efflux pump inhibitor. [ABSTRACT FROM AUTHOR]