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Biogenic fluorescent carbon dot-decorated mesoporous organosilica nanoparticles for enhanced bioimaging and chemotherapy
No full text[[abstract]]Hybrid materials possess the unique properties of their individual components, enabling their use in multiple synergistic applications. In this study, we synthesized biogenic fluorescent carbon dots (CDs) decorated with biodegradable periodic mesoporous organosilica nanoparticles (BPMO), creating BPMO@CDs. The CDs, approximately 9.8 nm in diameter, were derived from Musa paradisiaca cv. Awak juice using a rapid microwave method, exhibiting a spherical shape and green and red luminescence. The resulting BPMO@CDs are spherical, around 100 nm in size, and maintain high pore volume and surface area. The elemental chemical state in the BPMO@CDs remains consistent with that of pure BPMO. Our findings demonstrate that BPMO@CDs achieve efficient cellular uptake rates of 46.74% in MCF7 cells and 17.07% in L929 cells, with preserved fluorescence within the cells. The optical properties of the CDs are retained in the BPMO@CDs, allowing for detection upon cellular uptake. Additionally, when loaded with anticancer drugs, the BPMO@CDs significantly enhance the cytotoxicity against MCF7 breast cancer cells, highlighting their potential for synergistic bioimaging and chemotherapy applications
KIF2C promotes paclitaxel resistance by depolymerizing polyglutamylated microtubules
No full text[[abstract]]The long-term effectiveness of paclitaxel is limited by chemoresistance. In this study, we elucidate the molecular mechanism by which kinesin family member 2C (KIF2C), a well-known microtubule depolymerase, contributes to the development of chemoresistance in triple-negative breast cancer (TNBC). We observed elevated levels of KIF2C, tubulin tyrosination, and polyglutamylation in human and mouse breast cancer cells resistant to paclitaxel. Additionally, these chemoresistant cells possessed cross-resistance to diverse microtubule-targeting agents (MTAs). We demonstrated that KIF2C preferentially depolymerizes polyglutamylated tubulin, even in the presence of paclitaxel. To counter this, we developed 7S9, a chemical inhibitor of KIF2C, that prohibits the dissociation of KIF2C from microtubules. The combination of 7S9 and paclitaxel significantly reduced tumorigenesis in chemoresistant TNBC model in mice. Moreover, 7S9 diminished cancer cell chemoresistance to several clinically available MTAs. Our findings elucidate the molecular mechanism of KIF2C-mediated chemoresistance and highlight KIF2C as a promising target for combating cross-resistance in TNBC
[[alternative]]Methods and compositions enhancing survival and functionality of anti-tumor and anti-viral t cells
No full text[[abstract]]本發明係關於一種藉由誘使細胞內高度表現Akt分子以增強該等細胞之存活與功能性而達到抗腫瘤或抗病毒免疫活性的方法。Akt訊息傳遞路徑可防止免疫檢查點的表現，而使具抗原特異性的細胞毒殺型T淋巴細胞可免於在免疫抑制性微環境中耗竭。本發明亦揭示，Akt基因具有可應用於治療慢性病毒感染疾病或惡性腫瘤的T細胞輸入療法用以進行T細胞工程的潛在利用性
[[alternative]]Immunosuppressive cells and making methods and composition thereof
No full text[[abstract]]本發明係關於一種免疫抑制細胞，及該細胞之製造、組成與使用方法。該免疫抑制細胞係藉由將骨髓前驅細胞/體細胞培養在含有GRO趨化激素之培養基中而獲得的
Method of producing enriched exosomes
No full text[[abstract]]A method of producing induced exosomes, the method comprising: contacting an isolated population of stem cells with an amount of a prostaglandin E receptor 4 (EP4) antagonist effective for inducing release of exosomes, whereby induced exosomes are released from the stem cells, and isolating the induced exosomes
[[alternative]]Methods to enhance nerve regeneration utilizing neural stem cells and il12p40
No full text[[abstract]]The present application provides a composition and methods to enhance nerve regeneration utilizing at least one component of neural stem cells or IL12p40. The composition comprises neural stem cells and a neurotrophic factor, which is constructed by IL12p40 as at least one subunit. The methods to enhance nerve regeneration comprise providing a nerve regeneration composition comprising a neurotrophic factor containing IL12p40 as at least one subunit to a subject. The composition of the methods can further comprise neural stem cells
[[alternative]]Methods to enhance nerve regeneration utilizing neural stem cells and IL12P40
No full text[[abstract]]本發明係提供利用神經幹細胞或IL12p40之至少一組成分以促進神經再生之組成物及方法。該組成物係包括神經幹細胞及神經滋養因子，其係以IL12p40作為至少一次單元所構成。該促進神經再生之方法係包括提供一種神經再生組成物到一個體，其中該組成物係包括至少含有IL12p40作為一個次單元的神經滋養因子。於該方法中，該組成物可進一步包括神經幹細胞
利用神经干细胞与IL12p40增强神经再生的方法
No full text[[abstract]]本发明提供利用神经干细胞或IL12p40之至少一种组分以增强神经再生之组合物及方法。该组合物包含神经干细胞及神经营养因子，其由IL12p40作为至少一个亚基构成。该增强神经再生之方法包括给个体提供神经再生组合物，其中该组合物包含至少含有IL12p40作为一个亚基的神经营养因子。该方法的组合物可进一步包含神经干细胞
The effect of sodium-glucose cotransporter-2 inhibitors on graft survival and cardiorenal outcomes in patients with diabetes and heart transplantation
No full text[[abstract]]Background and aims: To compare the risk of graft survival, cardiovascular events, dialysis, and all-cause mortality between the use and non-use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the treatment of diabetes mellitus in patients with heart transplantation. Materials and methods: In this study, we analyzed the TriNetX collaborative network data. We identified 6494 patients who underwent heart transplantation between January 1, 2015, and December 31, 2022. From these patients, 1063 pairs of SGLT2i users and non-users were selected based on their respective propensity scores. We used the Kaplan-Meier method and Cox proportional hazards models to assess differences in the risk of outcomes between the two groups. Results: In the matched groups, SGLT2i users had a reduced risk of heart transplant failure and rejection (hazard ratio [HR]: 0.873, 95% confidence interval [CI]: 0.774-0.985), dialysis (HR: 0.566, 95% CI: 0.385-0.833), all-cause hospitalizations (HR: 0.822, 95% CI: 0.739-0.916), and all-cause mortality (HR: 0.767, 95% CI: 0.627-0.938) than non-users. However, there were no significant differences between the two groups in the risk of post-transplant sepsis or infection (HR: 0.891, 95% CI: 0.739-1.075), heart failure exacerbation (HR: 0.915, 95% CI: 0.733-1.144), and ischemic heart disease (HR: 1.044, 95% CI: 0.939-1.161). Conclusion: This multicenter cohort study showed that heart transplant recipients with diabetes mellitus treated with SGLT2i had a significant reduction in the risk of graft failure, need for dialysis, all-cause hospitalization, and mortality compared to those not treated with SGLT2i
A phase I/II study of nanoliposomal irinotecan and carboplatin in patients with advanced or metastatic, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma characterized by tissue and liquid next-generation sequencing
No full text[[abstract]]Background: For locally advanced or metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), standard chemotherapy typically incorporates etoposide or irinotecan plus platinum agents. Herein, we initiate a phase I/II trial to apply Nal-IRI in combination with carboplatin as the 1st line treatment in patients with GEP-NECs to define the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D). Methods: In the phase I part, traditional 3+3 design was applied. Enrolled patients would receive escalating dose of 60 (level -1), 80 (starting dose, level 0) or 100 (level 1) mg/m2 salt-form nal-IRI plus carboplatin AUC=4 with maximum total dose of 600 mg on D1, every 21 days as a cycle. DLTs were evaluated during the first one cycle of treatment with tumor assessment every 6 weeks. Prophylaxis G-CSF was not allowed in the first cycle Paired testing of tissue (TBx) and liquid biopsy (LBx) was done by Illumina TSO500 platform before treatment. The second LBx would be repeated for confirmed partial responders when progression. Results: Totally 6 GEP-NEC patients with primary sites of colon in three, and each one in esophagus, ampulla of Vater and pancreas were enrolled to level 0. One patient had DLT of grade 4 neutropenia lasting for 3 days even under salvage G-CSF. Treatment-related adverse events showed grade 3/4 neutropenia (33.4%), grade 2 anemia (16.7%), grade 3 fatigue (16.7%), and grade 2 skin rash (16.7%). Four patients achieved confirmed partial response and 2 patients got stable disease, with the objective response rate of 66.7% (95% confidence interval: 22%-96%). After the data and safety monitoring board meeting, level 0 was decided as RP2D but not escalation to level 1 because of acceptable toxicity profiles and promising efficacies. Comprehensive genomic profiling showed that driver mutations were identified in three cases including two harboring BRAFV600E mutation and one with KRASG12D mutation. The other three cases lacking driver mutation showed frequent copy number alteration including 1 with MDM2 amplification (copy number 27) and a wild-type TP53. Homologous recombination deficiency (HRD), as determined by GIS score, was identified in a colon GEP-NEC who remained to be HRD-positive at progression but a higher TMB (from 4.7 to 10.2 Muts/Mb) and a higher BRAFV600E mutation allele frequency (from 24.1% to 43.6%) in tumor tissue, compared to the baseline profiling. Conclusions: Based on current data, the RP2D is 80 mg/m2 of nal-IRI (salt-form) and carboplatin of AUC=4, every 3 weeks. The extension phase II study in GEP-NEC is ongoing. Clinical trial information: NCT05385861