Mesothelin-targeted CAR-NK Cells Derived From Induced Pluripotent Stem Cells Have a High Efficacy in Killing Triple-negative Breast Cancer Cells as Shown in Several Preclinical Models.

The emergence of immunotherapy has introduced a promising, novel approach to cancer treatment. While multiple chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable clinical efficacy against leukemia, their effect on solid tumors has been limited. One potential option for treating solid tumors is the engineering of natural killer (NK) cells with CARs. Mesothelin (MSLN), a tumor differentiation antigen, is expressed on triple-negative breast cancer (TNBC) cells, making it a potential target for CAR-NK therapy in the treatment of TNBC. We first constructed induced pluripotent stem cells with stable anti-MSLN-CAR expression and subsequently differentiated these cells into mesothelin-targeted CAR-NK (MSLN-NK) cells. We then assessed the effects of MSLN-NK cells on TNBC cells both in vitro (using the MDA-MB-231 cell line), in vivo (in a CDX mouse model), and ex vivo (using patient-specific primary cells and patient-specific organoids), in which MSLN surface expression was confirmed. Our CDX study results indicated that MSLN-NK cells effectively killed MDA-MB-231 (MD231) cells in vitro, reduced tumor growth in the CDX mouse model of TNBC, and lysed patient-specific primary cells and patient-specific organoids derived from the tumor samples of TNBC patients. Our data demonstrated that MSLN-NK cells had high efficacy on killing TNBC cells in in vitro, in vivo, and ex vivo. Therefore, MSLN-NK could be a promising treatment option for TNBC patients.

Atrial Fibrillation Risk and Urate-Lowering Therapy in Patients with Gout: A Cohort Study Using a Clinical Database.

Individuals of Asian descent are at higher risk for developing hyperuricemia and gout as compared to Western populations. Urate-lowering therapy (ULT) is an effective treatment for hyperuricemia and gout. It was reported that febuxostat, one of the ULTs, raises the risk of atrial fibrillation (AF) in elderly populations. Nevertheless, this association has not been properly investigated in Asian populations. We aimed to investigate the development of AF after ULT with different drugs in an Asian population. We conducted a retrospective cohort study using the clinical database at Kaohsiung Veterans General Hospital. Patients newly diagnosed with gout between 1 January 2013 and 31 December 2020 and with a documented baseline serum uric acid (sUA) level but no prior diagnosis of AF were identified. Patients were divided into three groups-allopurinol, benzbromarone, and febuxostat users. During the follow-up period, the risks of incident AF following the initiation of ULT with different drugs were assessed. Development of incident AF was noted in 43 (6%) of the 713 eligible patients during the follow-up period (mean, 49.4 ± 26.6 months). Febuxostat-treated patients had a higher prevalence of certain comorbidities (diabetes mellitus, heart failure, and chronic kidney disease) and higher CHA2DS2-VASc scores. Compared with allopurinol, neither febuxostat nor benzbromarone was associated with increased adjusted hazard ratios (HR) for incident AF (HR: 1.20, 95% confidence interval [CI]: 0.43-3.34; HR: 0.68, 95% CI: 0.22-2.08). There was no difference in the risk of incident AF among Asian patients with gout who received febuxostat, allopurinol, or benzbromarone. Further studies are needed to evaluate long-term cardiovascular outcomes in patients receiving different ULT drugs.

Utilizing Edible Agar as a Carrier for Dual Functional Doxorubicin-Fe3O4 Nanotherapy Drugs.

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both Fe3O4 and doxorubicin (DOX) with agar as the drug carrier to obtain DOX-Fe3O4@agar. The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, DOX-Fe3O4@agar reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.

Polydopamine Ultrathin Film Growth on Mica via In-Situ Polymerization of Dopamine with Applications for Silver-Based Antimicrobial Coatings.

The development of polydopamine (PDA) coatings with a nanometer-scale thickness on surfaces is highly desirable for exploiting the novel features arising from the specific structure on the molecular level. Exploring the mechanisms of thin-film growth is helpful for attaining desirable control over the useful properties of materials. We present a systematic study demonstrating the growth of a PDA thin film on the surface of mica in consecutive short deposition time intervals. Film growth at each deposition time was monitored through instrumental techniques such as atomic force microscopy (AFM), water contact angle (WCA) analysis, and X-ray photoelectron spectroscopy (XPS). Film growth was initiated by adsorption of the PDA molecules on mica, with subsequent island-like aggregation, and finally, a complete molecular level PDA film was formed on the surface due to further molecular adsorption. A duration of 60-300 s was sufficient for complete formation of the PDA layer within the thickness range of 0.5-1.1 nm. An outstanding feature of PDA ultrathin films is their ability to act as a molecular adhesive, providing a foundation for constructing functional surfaces. We also explored antimicrobial applications by incorporating Ag nanoparticles into a PDA film. The Ag NPs/PDA film was formed on a surgical blade and then characterized and confirmed by SEM-EDS and XPS. The modified film inhibited bacterial growth by up to 42% on the blade after cutting through a pork meat sample.

Preparation of vaterite calcium carbonate granules from discarded oyster shells as an adsorbent for heavy metal ions removal.

We used discarded oyster shells to prepare vaterite calcium carbonate microparticles and explored the removal effects and the underlying mechanism toward several heavy metal ions. The removal efficiency for each ion type was: Pb2+ (99.9%), Cr3+ (99.5%), Fe3+ (99.3%), and Cu2+ (57.1%). With the exception of Cu2+, vaterite calcium carbonate particles exhibited excellent removal performance on all tested heavy metal ions, with exceptional results for Pb2+. The factor affecting the removal efficiency of heavy metal ions is shown to involve an ion exchange reaction between calcium and the heavy metal ions resulting in recrystallization. Vaterite calcium carbonate particles prepared by this method have the advantage of low price, easy synthesis, and reduction of environmental waste. Thus, this procedure for synthesizing vaterite CaCO3 provides an environmentally responsible method for preparing materials that can be economically incorporated into common consumer products such as household drinking water filtration systems.

[Magnetic resonance-ultrasound fusion guided transperineal prostate biopsy for the diagnosis of prostate cancer].

OBJECTIVE: To investigate the application value of magnetic resonance-ultrasound fusion (MR-USF) guided transperineal prostate biopsy (TPPB) in the diagnosis of prostate cancer. METHODS: Relevant data were collected retrospectively from 77 patients undergoing MR-USF guided TPPB (n = 22) or 12-core systematic prostate biopsy (SPB) (n = 55) in Binhai People's Hospital from May to July 2019 and statistically analyzed using the software Graphad Prism 7.0 and SPSS 22.0. RESULTS: The patients were aged 51－91 (70.5 ± 9.7) years, with a mean PSA level of (35.1 ± 115.4) µg/L (1.02－959 µg/L) and an average prostate volume of (48.81 ± 38.4) cm3 (7.54－307.61 cm3). There were no statistically significant differences in age, PSA, and BMI between the two groups of patients (P > 0.05). Prostate cancer was confirmed in 31 of the cases, with a positive rate of 40.26% (31/77), significantly higher in the TPPB (45.45% ï¼»10/22ï¼½ than in the SPB group (38.18% ï¼»21/55ï¼½, P < 0.01). Based on the PI-RADS scores, the Gleason grade was also higher in the former than in the latter group. CONCLUSIONS: MR-USF guided TPPB can improve the biopsy performance. Whether it should be used is based on the patient's PSA level and PI-RADS scores.

[Combination of transrectal 125I seeds implantation brachytherapy and intermittent hormonal therapy for locally advanced prostate cancer].

OBJECTIVE: To evaluate the clinical efficacy of transrectal 125 I seeds implantation brachytherapy (BT) combined with intermittent hormonal therapy (IHT) in the treatment of locally advanced prostate cancer. METHODS: We treated 27 patients with locally advanced prostate cancer by transrectal 125I seeds implantation BT combined with IHT, and dynamically observed the changes in the PSA level, prostate volume, maximum urinary flow rate (Qmax) and International Prostate Symptoms Score (IPSS). RESULTS: All the implantation procedures were completed smoothly, lasting 20 to 35 minutes, with 40 to 58 seeds implanted. At 6 months after implantation, the PSA level was < 0.2 microg/L in all the patients (< 0.1 microg/L in 19 cases), the prostate volume was significantly reduced (P < 0.05), and Qmax and IPSS remarkably improved (P < 0.05). At 3 years after implantation, 19 cases were in the first cycle and the other 8 in the third cycle of IHT, of which 2 progressed to androgen-independent prostate cancer, and another 2 developed early bone metastasis. The rates of 3-year biochemically and clinically progression-free survival were 70.3% and 85.2%, respectively, and the rate of therapeutic effectiveness was 92.6%. No severe complications occurred in any of the cases. CONCLUSION: Transrectal 125I seeds implantation BT combined with IHT is a safe and minimally invasive procedure for locally advanced prostate cancer, which can effectively retard its clinical progression with no such complications as severe urethral, rectal or erectile dysfunction.

Dynamic Left Ventricular Outflow Tract Obstruction with Cardiogenic Shock in Apical Ballooning Syndrome.

UNLABELLED: Apical ballooning syndrome, also called Takotsubo cardiomyopathy, is characterized by transient systolic dysfunction of mid to apical segments and hyperkinesis of basal segments of the left ventricle that mimic acute myocardial infarction without significant coronary artery stenosis. We reported a 51-year-old man with chest distress, hypotension and abnormal electrocardiogram. Echocardiography revealed extensive akinesia of the mid to apical portions of the left ventricle, hyperkinesia of basal segments of the left ventricle, increasing left ventricle outflow tract velocity and severe mitral regurgitation. Cardiac catheterization showed a normal coronary angiography and an obvious pressure gradient between the left ventricle and aorta. After we discontinued administration of nitrates, provided mild hydration and initiated intravenous dopamine infusion, the patient's hypotension, left ventricular to aortic pressure gradient, and severe mitral regurgitation resolved the next day. Thereafter, apical ballooning syndrome with dynamic left ventricular outflow tract obstruction, severe mitral regurgitation and cardiogenic shock was diagnosed. KEY WORDS: Apical ballooning syndrome; Cardiogenic shock; Left ventricular outflow tract obstruction; Mitral regurgitation.