Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose-response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity.

OBJECTIVE: It has been reported that exhaustive exercise (EE) causes myocyte injury, and eventually damages the function of the myocardia. Albiflorin (AF) has anti-inflammatory, antioxidant, and anti-apoptosis effects. In this study, we determined whether AF could mitigate the EE-induced myocardial injury and research the potential mechanisms.
METHODS: The rat model of EE was built by forced treadmill running method. Rats were intraperitoneally injected with AF before EE once daily for one week. The relative factors levels were examined by commercial kits. The apoptosis was appraised using a TdT-mediated dUTP nick end labeling assay kit. The ACSL4, GPX4, Nrf2, pAKT/AKT, and HO-1 contents were assessed by western blot.
RESULTS: AF lessened EE-induced cardiac myocytes ischemic/hypoxic injury and reduced the contents of myocardial injury biomarkers in the serum. AF lessened EE-induced cardiac myocyte apoptosis, inflammatory response, oxidative stress, and ferroptosis in myocardial tissues. However, the influences of AF were overturned by the co-treatment of AF and LY294002. AF activated the AKT/Nrf2/HO-1 signaling pathway in myocardial tissues in vivo.
CONCLUSIONS: AF could curb cardiac myocytes ferroptosis, thus diminishing the EE-induced myocardial injury through activating the AKT/Nrf2/HO-1 cascade.

In this study, high-performance liquid chromatography was used to determine four components of Shaoyao Gancao Decoction (SGD), and the effect of purification was evaluated using fingerprints, similarity analysis and cell experiments. An effective method for isolation and purification of SGD was established. The adsorption/desorption properties of SGD were evaluated using resin screening, isothermal analysis, adsorption kinetics, and dynamic adsorption-desorption experiments. It was shown that the Langmuir equation fitted the isotherm data well and that a pseudo-second-order model accurately described kinetic adsorption on AB-8 resin. Analysis of thermodynamic parameters showed that the adsorption process was exothermic. Under the optimal process conditions, the concentrations of albiflorin, paeoniflorin, liquiritin and ammonium glycyrrhizinate in the product were 73.05, 134.04, 45.04 and 75.00 mg/g, respectively. The yields of the four components were 71.89 %-86.19 %. Cell experiments showed that the purified SGD retained anti-inflammatory activity. This research lays the foundation for the separation and purification of SGD and subsequent preparation research.

OBJECTIVE: This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above.
METHODS: This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score.
RESULTS: Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups.
CONCLUSIONS: Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients\' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.

Gene expression technology has become an indispensable tool for elucidating biological processes and developing biotechnology. Cell-free gene expression (CFE) systems offer a fundamental platform for gene expression-based technology, in which the reversible and programmable control of transcription can expand its use in synthetic biology and medicine. This study shows that CFE can be controlled via the host-guest interaction of cucurbit[7]uril (CB[7]) with N6-guest-modified adenosines. These adenosine derivatives were conveniently incorporated into the DNA strand using a post-synthetic approach and formed a selective and stable base pair with complementary thymidine in DNA. Meanwhile, alternate addition of CB[7] and the exchanging guest molecule induced the reversible formation of a duplex structure through the formation and dissociation of a bulky complex on DNA. The kinetics of the reversibility was fine-tuned by changing the size of the modified guest moieties. When incorporated into a specific region of the T7 promoter sequence, the guest-modified adenosines enabled tight and reversible control of in vitro transcription and protein expression in the CFE system. This study marks the first utility of the host-guest interaction for gene expression control in the CFE system, opening new avenues for developing DNA-based technology, particularly for precise gene therapy and DNA nanotechnology.

BACKGROUND: Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes implemented during the study. We present a process evaluation protocol of a home-based gait, balance, and resistance exercise intervention to ameliorate persistent taxane-induced neuropathy study according to 7 key elements of process evaluation.
METHODS: The process evaluation is conducted parallel to the longitudinal, randomized control clinical trial examining the effects of the home-based gait, balance, and resistance exercise program for women with persistent peripheral neuropathy following treatment with taxanes for breast cancer (IRB approval: Pro00040035). The flowcharts clarify how the intervention should be implemented in comparable settings, fidelity procedures help to ensure the participants are comfortable and identify their individual needs, and the process evaluation allows for the individual attention tailoring and focus of the research to avoid protocol deviation.
CONCLUSIONS: The publication of the evaluation protocol plan adds transparency to the findings of clinical trials and favors process replication in future studies. The process evaluation enables the team to systematically register information and procedures applied during recruitment and factors that impact the implementation of the intervention, thereby allowing proactive approaches to prevent deviations from the protocol. When tracking an intervention continuously, positive or negative intervention effects are revealed early on in the study, giving valuable insight into inconsistent results. Furthermore, a process evaluation adds a participant-centered element to the research protocols, which allows a patient-centered approach to be applied to data collection.
BACKGROUND: ClinicalTrials.gov NCT04621721, November 9, 2020, registered prospectively.
METHODS: April 27, 2020, v2.

OBJECTIVE: Treatment with taxanes can result in chemotherapy-induced peripheral neuropathy (CIPN). We investigated the efficacy and safety of mirogabalin for the treatment of CIPN in patients who had been administered perioperative chemotherapy including taxane-based agents for breast cancer.
METHODS: We retrospectively analyzed the case of 43 patients with early breast cancer who received a taxane as perioperative chemotherapy and were administered mirogabalin at the diagnosis of CIPN.
RESULTS: Thirty-six patients (83.7%) had grade 1 CIPN and the other seven patients (16.3%) had grade 2 CIPN. The median mirogabalin dose was 10 mg (5-30 mg). CIPN improved from grade 1 to 0 in 12 patients (27.9%) and from grade 2 to 1 in one patient (2.3%); 13 (30.2%) patients thus had an objective therapeutic response. There were no cases in which chemotherapy was reduced or discontinued due to CIPN. Adverse events were evaluated by Common Terminology Criteria for Adverse Events and included five cases of dizziness (11.7%), three of somnolence (7.0%), and two of nausea (4.7%), all of which were grade ≤2. There were no cases of serious (grade ≥3) adverse effects.
CONCLUSIONS: Mirogabalin may be effective and safe for treating CIPN of patients who receive a taxane in a perioperative breast cancer setting.

Triple-negative breast cancer (TNBC) patients are treated with traditional chemotherapy, such as the taxane class of drugs. One such drug, paclitaxel (PTX), can be effective in treating TNBC; however, many tumors will develop drug resistance, which can lead to recurrence. In order to improve patient outcomes and survival, there lies a critical need to understand the mechanism behind drug resistance. Our lab made the novel observation that decreased expression of the Adenomatous Polyposis Coli (APC) tumor suppressor using shRNA caused PTX resistance in the human TNBC cell line MDA-MB-157. In cells lacking APC, induction of apoptosis by PTX was decreased, which was measured through cleaved caspase 3 and annexin/PI staining. The current study demonstrates that CRISPR-mediated APC knockout in two other TNBC lines, MDA-MB-231 and SUM159, leads to PTX resistance. In addition, the cellular consequences and molecular mechanisms behind APC-mediated PTX response have been investigated through analysis of the BCL-2 family of proteins. We found a significant increase in the tumor-initiating cell population and increased expression of the pro-survival family member Bcl-2, which is widely known for its oncogenic behavior. ABT-199 (Venetoclax), is a BH3 mimetic that specifically targets Bcl-2. ABT-199 has been used as a single or combination therapy in multiple hematologic malignancies and has shown promise in multiple subtypes of breast cancer. To address the hypothesis that APC-induced Bcl-2 increase is responsible for PTX resistance, we combined treatment of PTX and ABT-199. This combination treatment of CRISPR-mediated APC knockout MDA-MB-231 cells resulted in alterations in apoptosis, suggesting that Bcl-2 inhibition restores PTX sensitivity in APC knockout breast cancer cells. Our studies are the first to show that Bcl-2 functional inhibition restores PTX sensitivity in APC mutant breast cancer cells. These studies are critical to advance better treatment regimens in patients with TNBC.

UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. The effects of supplemental ultraviolet-B (sUV-B) exposure (T1, 1.40 kJ·m-2·day-1; T2, 2.81 kJ·m-2·day-1; and T3, 5.62 kJ·m-2·day-1) on the growth biomass, physiological characteristics, and secondary metabolites were studied. Our results indicated that leaf thickness was significantly (p < 0.05) reduced under T3 relative to the control (natural light exposure, CK); The contents of 6-BA and IAA were significantly reduced (p < 0.05); and the contents of ABA, 10-deacetylbaccatin III, and baccatin III were significantly (p < 0.05) increased under T1 and T2. The paclitaxel content was the highest (0.036 ± 0.0018 mg·g-1) under T3. The cephalomannine content was significantly increased under T1. Hmgr gene expression was upregulated under T1 and T3. The gene expressions of Bapt and Dbtnbt were significantly (p < 0.05) upregulated under sUV-B exposure, and the gene expressions of CoA, Ts, and Dbat were significantly (p < 0.05) downregulated. A correlation analysis showed that the 6-BA content had a significantly (p < 0.05) positive correlation with Dbat gene expression. The IAA content had a significantly (p < 0.05) positive correlation with the gene expression of Hmgr, CoA, Ts, and Dbtnbt. The ABA content had a significantly (p < 0.05) positive correlation with Bapt gene expression. Dbat gene expression had a significantly (p < 0.05) positive correlation with the 10-deacetylbaccatin content. Hmgr gene expression was positively correlated with the contents of baccatin III and cephalomannine. Bapt gene expression had a significantly (p < 0.01) positive correlation with the paclitaxel content. A factor analysis showed that the accumulation of paclitaxel content was promoted under T2, which was helpful in clarifying the accumulation of taxane compounds after sUV-B exposure.

BACKGROUND: Male breast cancer (MBC) is a rare disease. Although several large-scale studies have investigated MBC patients in other countries, the features of MBC patients in China have not been fully explored. This study aims to explore the features of Chinese MBC patients comprehensively.
METHODS: We retrospectively collected data of MBC patients from 36 centers in China. Overall survival (OS) was evaluated by the Kaplan-Meier method, log-rank test, and Cox regression analyses. Multivariate Cox analyses were used to identify independent prognostic factors of the patients.
RESULTS: In total, 1119 patients were included. The mean age at diagnosis was 60.9 years, and a significant extension over time was observed (P < 0.001). The majority of the patients (89.1 %) received mastectomy. Sentinel lymph node biopsy was performed in 7.8 % of the patients diagnosed in 2009 or earlier, and this percentage increased significantly to 38.8 % in 2020 or later (P < 0.001). The five-year OS rate for the population was 85.5 % [95 % confidence interval (CI), 82.8 %-88.4 %]. Multivariate Cox analysis identified taxane-based [T-based, hazard ratio (HR) = 0.32, 95 % CI, 0.13 to 0.78, P = 0.012] and anthracycline plus taxane-based (A + T-based, HR = 0.47, 95 % CI, 0.23 to 0.96, P = 0.037) regimens as independent protective factors for OS. However, the anthracycline-based regimen showed no significance in outcome (P = 0.175).
CONCLUSIONS: As the most extensive MBC study in China, we described the characteristics, treatment and prognosis of Chinese MBC population comprehensively. T-based and A + T-based regimens were protective factors for OS in these patients. More research is required for this population.