Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors.

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia.

The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague-Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.

The Clinical Efficacy of Punch Excision Combined With Intralesional Steroid Injection for Keloid Treatment.

BACKGROUND: Conservative and nonconservative treatments are available for keloids. However, few studies have explored the effectiveness of punch excision in keloid treatment. OBJECTIVE: This study aimed to investigate the efficacy and safety of punch excision combined with intralesional steroid injection for keloid treatment. METHODS: In this prospective, randomized, controlled trial, 81 patients were randomly divided into 2 groups. The patients in the treatment group were initially treated with punch excision combined with intralesional steroid injection, followed by injection treatment alone. The patients in the control group received intralesional steroid injection alone. The keloid thickness before and after the punch excision was evaluated; the keloid scores at different time points and the number of injection treatments required in both groups were compared, and adverse reactions were observed. RESULTS: The mean thickness after punch excision was lower (p < .05), injection treatments were fewer (p < .05), keloid scores were significantly lower (p < .05), and incidence rate of long-term adverse effects was lower in the treatment group than in the control group (p < .05). CONCLUSION: The combination of punch excision and intralesional steroid injection has a notable therapeutic effect on keloids, shortening the treatment course without evident adverse reactions.

Comparison of Neoadjuvant Chemotherapy Efficiency in Advanced Ovarian Cancer Patients Treated With Paclitaxel Plus Carboplatin and Intraperitoneal Bevacizumab vs. Paclitaxel With Carboplatin.

Objective: This study evaluated the role of neoadjuvant chemotherapy (NACT) with bevacizumab intraperitoneal perfusion in advanced ovarian cancer (AOC). Methods: In this study, 80 patients with advanced epithelial ovarian cancer (stage IIIc or IV) who received NACT at the Central Hospital of Zhuzhou between February 2019 and October 2020 were enrolled. Patients were randomized to receive paclitaxel plus carboplatin (TC) or TC plus intraperitoneal perfusion of bevacizumab (TCB). The effect of chemotherapy was assessed following two cycles of chemotherapy. Cancer antigen 125 (CA125), tumor size, ascites volume, bleeding volume, duration of operation, surgical satisfaction rate, complication rate, and residual tumor were assessed to monitor response to chemotherapy. Results: Treatment with TCB regimen significantly reduced serum levels of CA125 and ascites volume (p < 0.001). Meanwhile, the TCB group had significantly lower intraoperative blood loss and shorter operation time (p < 0.001). Most importantly, patients treated with TCB regimen had a higher surgical satisfaction rate (p < 0.01). Moreover, the incidence of postoperative wound infection, hypoproteinemia, abdominal distension, and fever was lower in the TCB group compared with the TC group. Assessment of adverse reactions during chemotherapy showed no severe complications between the two groups. Conclusions: The results demonstrated that the TCB regimen is superior to the TC regimen alone in the treatment of AOC. These findings could help improve the surgical satisfaction rate, provide more effective treatment strategies to prolong progression-free survival and reduce postoperative complications, and promote surgical recovery in AOC.

Rapid characterization of woody biomass digestibility and chemical composition using near-infrared spectroscopy.

Rapid determination of the properties of lignocellulosic material is highly desirable for biomass production and utilization. In the present study, measurements of woody biomass digestibility and chemical composition using near-infrared reflectance (NIR) spectroscopy were calibrated. Poplar and eucalyptus materials were recorded in NIR spectrum as well as determined for their chemical compositions of Klason lignin, α-cellulose, holocellulose, lignin syringyl/guaiacyl (S/G) ratio and enzymatic digestibility. Fitting of the NIR information with chemical properties and digestibility by partial least-squares (PLS) regression generated a group of trained NIR models that were able to be used for rapid biomass measurement. Applying the models for woody biomass measurements led to a reliable evaluation of the chemical composition and digestibility, suggesting the feasibility of using NIR spectroscopy in the rapid characterization of biomass properties.

Thyroid carcinoma with bone metastases: a prognostic factor study.

OBJECTIVE: Occult clinical presentations usually hinder the early detection and management of patients with bone metastases from thyroid carcinoma. We retrospectively investigated the clinical outcomes of such patients from 1993 to 2004 and analyzed the prognostic parameters. DESIGN: The basic demographic data and manifestations of 44 patients who had thyroid carcinoma with bone metastases were reviewed. We studied the gender, age, locations of metastases, histological types, treatment methods, hypercalcemic episodes and results of treatments. We used Kaplan-Meier survival analysis and log-rank tests to access the statistical significance. MAIN OUTCOME: The incidence of bone metastasis from thyroid carcinomas in this series was 5.0%. Twenty patients (45.4%) had follicular, 16 (36.3%) had papillary, 3 (6.8%) had anaplastic, 3 (6.8%) had medullary, and 2 (4.5%) had Hurthel cell carcinomas. Twelve patients had hypercalcemic episodes, ranging from 2.6 to 2.9 mmolL(-1) (mean ± SD: 2.68 ± 0.15 mmolL(-1)). Survival time after bone metastases ranged from 2 months to 8 years (mean ± SD: 5.3 ± 1.3 years). The 5-year survival rate was 79.4% and the 10-year survival rate was 52.9%. Regarding the histological cancer type, patients with papillary and follicular cancers survived significantly longer than those with anaplastic and medullary cancers (p < 0.05). In addition, the patients presenting with hypercalcemia had the worst survival (p < 0.05). CONCLUSIONS: Thyroid carcinoma can present with bone metastases in its early stage. We found that both tumor type and hypercalcemia were significant prognostic factors for survival time.