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The influence of the glutathione C60 derivative on the cytotoxicity of a highly reactive free radical NO (nitric oxide) has been investigated. Consistent with its cytoprotective abilities, the derivative scavenges ROS (reactive oxygen species) and RNS (reactive nitrogen species) both in vitro and under cell-free conditions. Moreover, the glutathione C60 derivative protected PC12 cells from the cytotoxic effect of the NO-releasing compound, SNP (sodium nitroprusside). Addition of glutathione C60 derivative alone did not induce apoptosis and necrosis. The results suggest that the glutathione C60 derivative has the potential to prevent NO-mediated cell death without evident toxicity. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hemin was extrinsically labeled by 58Fe avoiding endogenous interference. [•] Mass spectrometric conditions were optimized using collision cell technology. [•] A mathematical correction equation was used to compensate for interference. [•] Isotope concentration, not ratio was treated as information for absorption study. [•] A new ICP-MS method was developed for pharmacokinetic study of iron preparations. [ABSTRACT FROM AUTHOR]

Abstract: Graphene oxide/TiO2 hybrid (GOT) was prepared by using Ti(OC4H9)4 and graphene oxide (GO) as reactants. Superior adsorption and photocatalysis performance under visible radiation were achieved in the presence of the GOT rather than in unmodified TiO2. GO that no toxicity in vitro acted as electron sink in GOT efficiently enhance the photodynamic activities. Consistent with photocatalytic performance of TiO2, GOT generated reactive oxygen species after visible light irradiation both in cell free condition and in vitro. No dark cytotoxicity was observed using 0–100μg/mL GOT during long incubation time. In parallel, following exposure of cells to GOT and irradiation, a marked decrease in mitochondrial membrane potential, cell viability, activities of superoxide dismutase, catalase and glutathione peroxidase, as well as increased malondialdehyde production were observed. Moreover, GOT caused significant elevation in caspase-3 activity, and induced apoptotic death. The results indicated that GOT had excellent photodynamic anticancer activity without dark cytotoxicity. [Copyright &y& Elsevier]

DJT1116PG, which selectively inhibits renal glucose reabsorption by inhibiting sodium-glucose cotransporter type 2, was developed as an insulin-independent treatment for type 2 diabetes mellitus. This Phase I trial evaluated the pharmacokinetic and pharmacodynamic properties of DJT1116PG at steady state in healthy Chinese individuals. This was a multiple ascending dose study of DJT1116PG (20, 50, and 100 mg once daily for 7 days) that included 36 healthy individuals. There were no serious adverse events or deaths in these studies, and no adverse event led to study discontinuation. Oral DJT1116PG was rapidly absorbed with a T max of 0.75–1.5 h and a t ½ of 12–16.2 h. Systemic exposure (C max and AUC) of DJT1116PG and its inactive metabolites (T1444, T1454, and T1830) increased in a dose-dependent manner. Urinary glucose excretion (UGE) plateaued at 50 mg of DJT1116PG in a previous single ascending dose study and on day 1 of this study. UGE plateaued at 20 mg of DJT1116PG on day 7 of this study. Serum glucose parameters were similar in individuals who received DJT1116PG or placebo. DJT1116PG was well tolerated in healthy Chinese individuals. At steady state, UGE plateaued at 20 mg of DJT1116PG in these individuals. These findings will inform the selection of doses for further early-stage clinical trials of DJT1116PG. Chinese Drug Trial Identifier: CTR20160986. [ABSTRACT FROM AUTHOR]

This study compared the safety and pharmacokinetics of a single oral dose of onradivir, an inhibitor of polymerase basic protein 2 in influenza A virus, in patients with hepatic impairment and healthy participants with normal hepatic function. Eight participants with mild hepatic impairment (Child-Pugh A), eight participants with moderate hepatic impairment (Child-Pugh B), and eight healthy matched controls were enrolled in this open-label, parallel-group clinical trial. After the administration of 600 mg of onradivir, pharmacokinetic parameters were calculated for each cohort and compared. Onradivir was generally well tolerated by all participants. No serious adverse events (AEs) and no deaths were reported during the study. Six patients with moderate hepatic impairment and three patients with mild hepatic impairment reported AEs, all of which were mild and quickly resolved. Compared with the normal liver function group, the maximum concentration, area under the curve from time zero to the last measurable concentration, and area under the curve from time zero to infinity were 103%, 68.5%, and 69.2% higher, respectively, in the mild hepatic impairment group. In the moderate hepatic impairment group, these increases were 101%, 197%, and 204%, respectively. Overall, there were clinically relevant differences in onradivir exposure between patients with mild or moderate hepatic impairment and normal controls. These data imply that onradivir dose adjustment is warranted in patients with mild or moderate hepatic impairment. The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05856513)., (© 2024, The American College of Clinical Pharmacology.)

Background: Previous studies have identified the antecedents of the lifestyle of many patients with chronic diseases. However, the mechanism of social support affecting the lifestyle of patients with chronic diseases is unclear, and the role of health literacy in social support affecting the lifestyle of patients with chronic diseases has not been found. Therefore, this study aims to explore the status quo of social support, health literacy and healthy lifestyle of patients with chronic diseases in China and the relationship among them., Methods: Through convenient sampling, 356 patients with chronic diseases were surveyed using a health promoting lifestyle scale, a chronic disease patients' health literacy scale and a social support scale., Results: There was a pairwise positive correlation between social support, health lifestyle and health literacy (R = 0.397,0.356,0.556, P < 0.01). After controlling gender, age and education level, it is found that social support has a positive impact on health lifestyle, and health literacy plays an intermediary role between social support and health lifestyle, accounting for 45.78 % of the total effect., Conclusion: To promote the healthy lifestyle of patients with chronic diseases and delay the development of the disease, we should strengthen social support for patients with chronic diseases; We should simultaneously take various measures to improve their health literacy., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study aims to investigate the underlying characteristics of spontaneous brain activity by analyzing the volumes of the hippocampus and parahippocampal gyrus, as well as the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), in order to differentiate between bipolar disorder (BD) and unipolar depressive disorder., Methods: A total of 46 healthy controls, 58 patients with major depressive disorder (MDD), and 61 patients with BD participated in the study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. The researchers calculated the differences in volume, fALFF, and ReHo values among the three groups. Additionally, they conducted correlation analyses to examine the relationships between clinical variables and the aforementioned brain measures., Results: The results showed that the BD group exhibited increased fALFF in the hippocampus compared to the healthy control (HC) and MDD groups. Furthermore, the ReHo values in the hippocampus and parahippocampal gyrus were significantly higher in the BD group compared to the HC group. The findings from the person correlation analysis indicated a positive relationship between ReHo values in the hippocampus and both HAMD and HAMA scores. Moreover, there was no correlation between the volumes, fALFF, and ReHo values in the hippocampus and parahippocampal gyrus, and cognitive function levels (RBANS)., Conclusion: Taken together, these aberrant patterns of intrinsic brain activity in the hippocampus and parahippocampal gyrus may serve as quantitative indicators for distinguishing between BD and unipolar depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Wen, Liu, Li, He, Liang and Huang.)

The purpose of this study was to determine the effect of amiodarone (Ami) on hERG-T618I currents in HEK293 cells. A transient transfection method was used to transfer hERG-T618I and hERG wild-type (WT) channel plasmids into HEK293 cells. An extracellular local perfusion method was used for administration. Currents were recorded using the whole-cell patch clamp technique. Ami (10 μM) had a greater retarding effect on the hERG-T618I channel than WT ( P < 0.05). The half-inhibitory concentration for the mutant was approximately 1.82 times that of WT ( P < 0.05). The WT current inhibition fraction against Ami was significantly greater than T618I in the same cell ( P < 0.05). The STEP current of the mutant channel was larger than the WT channel, but the characteristic of inward rectification did not appear. Ami reduced the STEP current of the mutant channel, and the steady-state activation curve indicated that channel activation decreased ( P > 0.05). Ami restored partial inactivation of the mutant channel. Ami effectively reduced the current in the phase 2 plateau ( P < 0.05), but the phase 3 current did not exhibit the characteristics of a WT current. Ami inhibited hERG-T618I currents on HEK293 cells, but the effect was weaker than WT., Competing Interests: Conflict of interest: Authors state no conflicts of interests., (© 2023 the author(s), published by De Gruyter.)

Background: Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB., Methods: This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days., Results: Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC 50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26-1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log 10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log 10 copies/mL, respectively., Conclusions: Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection., Trial Registration: ClinicalTrials.gov, number NCT05470829)., (© 2023. The Author(s).)

Objective: We aimed to evaluate the similarity of BAT2206 to its originator, ustekinumab, including pharmacokinetic profiles, immunogenicity, and safety in healthy Chinese male subjects., Methods: This was a double-blinded, randomized, single-dose, parallel-group clinical trial, in which 270 healthy male subjects were enrolled to receive a single subcutaneous injection (45 mg) of either BAT2206 or ustekinumab (European Union or USA) at a 1:1:1 ratio. The pairwise pharmacokinetic similarities and the safety and immunogenicity of both drugs were evaluated and compared., Results: The results showed that the 90% confidence interval of the geometric mean ratio for primary pharmacokinetic parameters (maximum plasma concentration and area under the plasma concentration-time curve from time zero to infinity) among BAT2206 and ustekinumab (USA or European Union sourced) groups were all within the predefined equivalent interval of 80-125%. Furthermore, all the groups had similar incidences of treatment-emergent adverse events, in which the majority of cases belonged to Common Terminology Criteria for the Classification of Adverse Events Grade 1 or 2. Anti-drug antibodies were detected in 54 (20.1%) subjects, namely 24 (26.7%), 13 (14.8%), and 17 (18.9%) patients in the BAT2206, ustekinumab (European Union), and ustekinumab (USA) groups, respectively. In contrast, the incidences of positive neutralizing antibodies were similar among the three groups., Conclusions: Pharmacokinetic similarity between BAT2206 and ustekinumab (USA or European Union sourced) was confirmed. The three groups had similar safety profiles, and the investigational drugs were well tolerated by subjects., Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT04371185)., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Forsythin, an active compound from Forsythiae Fructus, has the potential to treat the common cold and influenza through its antipyretic-analgesic, anti-inflammatory and antiviral effects. The safety, tolerability and pharmacokinetic (PK) profile of forsythin were evaluated in healthy Chinese subjects., Methods: This phase 1a study included three parts: double-blind, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 400, 600 or 800 mg), food effect investigation (100 mg) and multiple-ascending-dose (MAD) (50, 100 or 200 mg TID for 5 days)., Results: Forsythin is safe and tolerable in healthy Chinese subjects. The rates of adverse events (AEs) in the forsythin cohort were similar to those in the placebo cohort. Forsythin is well-absorbed after single or multiple doses and is extensively metabolized. The primary metabolites were aglycone M1, M1 sulphate (M2) and M1 glucuronide (M7). Exposure to forsythin (100 mg) was higher after food intake by approximately 1.4-fold, whereas M2 and M7 did not change. The steady state was reached around three days in the MAD study. Forsythin, M2 and M7 accumulation on day 5 was 1, 3 and 2, respectively., Conclusions: The safety and PK profiles of forsythin support further evaluation of its efficacy in individuals with the common cold or influenza.

Background: TQA3526 is a novel farnesoid X receptor agonist developed to treat non-alcoholic steatohepatitis (NASH) or primary biliary cholangitis (PBC). This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TQA3526 in healthy Chinese patients. Methods: Healthy subjects aged 18-55 years were enrolled in this double-blinded, first-in-human, placebo-controlled single ascending dose (1, 2, 5, and 10 mg) comprising food effect investigation (10 mg) and multiple dose study (2 mg and 0.2 + 0.5 + 1 mg). Safety was assessed on the basis of adverse events. The TQA3526 concentrations were analysed in the PK study. Alkaline phosphatase (ALP), fibroblast growth factor-19 (FGF19), bile acid precursor C4 (7α-hydroxy-cholest-4-ene-3-one), cholesterol, and bile acid were selected for PD analysis. Results: TQA3526 was well tolerated, and the primary adverse drug reaction was pruritus, as expected. The exposure to TQA3526 increased in a dose-dependent manner after a single dose of 1-10 mg. The exposure was higher after food intake. A steady state was reached around 5 days, and obvious plasma accumulation of TQA3526 was observed in the multiple dose study. TQA3526 increased circulating FGF-19 and decreased C4 levels in a dose-dependent manner. ALP increased only mildly in the 2 mg multiple dose cohort. Conclusions: TQA3526 (<10 mg/day) was safe and tolerable in healthy Chinese subjects. The safety profile and PK/PD characteristics of TQA3526 support further evaluation of patients with NASH or PBC. This study was registered at https://www.chictr.org.cn/ under the identifier ChiCTR1800019570.

Background: The primary objective of this study was to investigate if hepatic impairment alters the safety, pharma c okinetics, and pharmacodynamics of HSK3486., Research Design and Methods: This was a clinical trial of HSK3486 in subjects with normal hepatic function ( n  = 8), and mild (Child-Pugh A; n  = 8), or moderate (Child-Pugh B; n  = 8) hepatic impairment. Each subject received an IV bolus dose of 0.4 mg/kg HSK3486 for 1 min, immediately followed by a maintenance infusion of 0.4 mg/kg/h HSK3486 for 30 min., Results: In total, 24 subjects were enrolled and completed the study. HSK3486 was generally well tolerated by all subjects. There were no serious AEs and no deaths reported during the study. The incidence of AEs was numerically highest in subjects with moderate hepatic impairment. The exposure (AUC) of HSK3486 increased gradually with the decrease in hepatic function; however, degree of hepatic impairment had little effect on HSK3486 PD (MOAA/S and BIS)., Conclusions: Overall, there were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to normal control. These data imply that HSK3486 dose adjustment is not warranted in subjects with mild or moderate hepatic impairment., Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04145596).Key MessageHSK3486 at an IV bolus dose of 0.4 mg/kg and a maintenance infusion of 0.4 mg/kg/h was safe and well tolerated by all mild or moderate hepatic impairment subjects and normal hepatic function subjects.There were no clinically relevant differences in HSK3486 exposure or PD in subjects with mild or moderate hepatic impairment compared to subjects with normal hepatic function.HSK3486 dose adjustment is not required in subjects with mild or moderate hepatic impairment.

Objective: KN015 is a long-acting, recombinant human follicle-stimulating hormone Fc fusion protein that induces follicle development. This first-in-human study evaluated the effect of KN015 on healthy, pituitary-suppressed women and examined its pharmacokinetics, pharmacodynamics, and tolerability., Methods: This phase I study was a double-blind, randomized, and placebo-controlled design with a single ascending dose (20, 40, and 60 μg, respectively)., Results: After subcutaneous administration of a single dose, the maximum serum KN015 concentrations reached 1.57, 2.78, and 3.62 ng/mL, respectively, after baseline adjustment. Over this dose range, the median T max occurred at 240-312 h, and the half-life (t ½ ) was 752-1160 h. Dose proportionality was shown across the studied dose range. In most subjects, follicular growth was observed, and the number and diameter of the follicles increased with an increasing dose. In the 40-μg and 60-μg groups, the mean numbers of follicles with a diameter of ≥17 mm were 3 and 4, respectively. There was no significant difference in adverse events between the KN015 and placebo groups. KN015 antibody was not detected in any of the dosage groups., Conclusion: The administration of a single ascending dose of KN015 was tolerated and able to induce follicular growth., Trial Registration: This trial is registered at the Chinese Clinical Trials website (http://www.chinadrugtrials.org.cn/index.html # CTR20160741) and ClinicalTrials.gov (https://clinicaltrials.gov/ # NCT03192527).

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open-label, randomized, single-dose, 3-way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250-mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects. This study aimed to support a generic consistency evaluation program, initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the within-subject standard deviation for area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within-subject SDs for serum peak concentration in the fasted condition, area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population., (© 2022 Pfizer (China) Research and Development Co. Ltd. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant., (© 2022 The Authors. Small Methods published by Wiley-VCH GmbH.)

Background: Thalassemia is one of the most common genetic diseases in southern China. Accurate population frequency data regarding the occurrence and distribution of thalassemia are important for designing appropriate prevention strategies for thalassemia. This study aims to reveal the molecular spectrum, ethnic and geographical distribution of thalassemia in the southern area of Hainan Province, China., Methods: A total of 9813 suspected carriers of thalassemia were screened for genetic analysis by using the PCR-reverse dot blot hybridization method targeting three known deletions of α-thalassemias (-- SEA , -α 3.7 , and -α 4.2 ), three nondeletional mutations of α-thalassaemias (α CS , α QS , and α WS ) and the 17 most common mutations of β-thalassaemias in the Chinese population., Results: Approximately 6,924 subjects were genetically diagnosed as thalassemia carriers or patients, including 5812 cases of α-thalassemia (83.9%), 369 cases of β-thalassemia (5.3%), and 743 cases of α-composite β-thalassemia (10.7%). A total of 21 distinct genotypes were identified among the 5,812 α-thalassemia carriers, -α 4.2 /αα, -α 3.7 /αα, and -α 3.7 /-α 4.2 were the most common α-thalassemia genotypes. The most frequent β-thalassemia genotype was β CD41-42 /β N , with a notable proportion of 69.6%, followed by the β -28 M /β N , β IVS-II-654 /β N , β CD71-72 /β N , β E /β N , and β CD17 /β N genotypes. In addition, 37 genotypes were detected among the 743 cases of both α- and β-thalassemia mutations. The α-thalassemia genotypes were most commonly found in the Li people, who accounted for 73.5% of α-thalassemia carriers. The β-thalassemia genotypes were most commonly identified in the Han people, who accounted for 59.4% of β-thalassemia carriers. Among the subjects carrying both α- and β-thalassemia variations, only three ethnic minorities were identified, including the Li, Han, and Miao people, accounting for 82.0, 17.4, and 0.7%, respectively., Conclusions: Our study indicates that there is high genetic heterogeneity, geographical and ethnic differences in thalassemia in populations in the southern area of Hainan Province. These findings will be helpful in guiding genetic counseling and prenatal diagnosis of thalassemia in Hainan Province., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Lu, Gao, Li, Li, Wang, Wei, Lu and You.)

Objective: Hepenofovir, a novel hepatic targeting prodrug of tenofovir, has been developed for the treatment of chronic hepatitis B (CHB). This is a first-in-human study to evaluate the pharmacokinetics (PK) and tolerability of single and multiple escalating doses of hepenofovir in healthy Chinese subjects. Methods: This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (25-200 mg) study under fasted conditions comprising a food-effect investigation (200 mg) and a multiple-ascending-dose (MAD) (25 mg) study under fasted conditions. Results: Hepenofovir was well tolerated in healthy Chinese subjects. There was no significant difference in adverse reaction rates between hepenofovir and placebo groups. Hepenofovir was rapidly absorbed and metabolized into tenofovir after dosing. In healthy participants, the median T max of hepenofovir and tenofovir was 0.33-0.50 h and 0.62-0.75 h, respectively, and their mean half-life was 2.5-12.3 h and 49.7-53.8 h, respectively. Systemic exposure to tenofovir increased in proportion to the dose. The mean accumulation indexes of hepenofovir and tenofovir were 1.1 vs. 1.8. Moreover, food could reduce the C max of both hepenofovir and tenofovir, but did not affect their area under the curve (AUC). Conclusions: Hepenofovir has shown a favorable safety and PK profile, which support the further evaluation of its safety and efficacy in CHB patients. Clinical trial registration number: The trial is registered at Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20191953)., Competing Interests: WG, YW, ZG, LH, DW, and WJ are employed by Xi’an Xintong Pharmaceutical Research Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Gao, Lou, Wu, Chen, Yang, Liu, Zhu, Li, Li, Wang, Liu, Guo, Wang, Gao, Han, Wang, Jin and Ding.)

Background: Psychological distress (depression, anxiety and stress) is more common among medical students than in the general population, and is an important cause of insomnia, internet addiction, substance abuse, decreased academic performance and increased suicidality in medical students., Methods: To examine the mechanism by which regulatory emotional self-efficacy affects medical students' psychological distress, a questionnaire of 539 medical students using an interpersonal adaptability scale, regulatory emotional self-efficacy scale, self-acceptance scale and depression-anxiety-stress scale was conducted., Results: ① Regulatory emotional self-efficacy, interpersonal adaptability and self-acceptance are positively correlated, but they are negatively correlated with psychological distress. ② The mediation model shows that interpersonal adaptation and self-acceptance are the mediation variables of the effect of regulatory emotional self-efficacy on psychological distress, and the total mediation effect value is -0.37, accounting for 86.05% of the total effect (-0.43). Specifically, the effect involves three paths: first, regulatory emotional self-efficacy indirectly affects psychological distress through interpersonal adaptation (effect value-0.24); second, regulatory emotional self-efficacy indirectly affects psychological distress through interpersonal adaptation and self-acceptance (effect value-0.08); and third, regulatory emotional self-efficacy indirectly affects psychological distress through self-acceptance (effect value -0.05)., Conclusions: Interpersonal adaptation and self-acceptance have a significant mediating effect between regulatory emotional self-efficacy and psychological distress, and the chain mediating effect of interpersonal adaptation and self-acceptance is also significant., (© 2022. The Author(s).)

Background: This study aimed to explore the effects of Kangdaxin oral liquid on myocardial fibrosis in heart failure with preserved ejection fraction (HFpEF) rats., Methods: A total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups Sham operation group (Sham), HFpEF group (HFpEF), and HFpEF with drug intervention group (HFpEF + I). Rats in HFpEF + I group were given Kangdaxin oral liquid at a dose of 2.7 mL/(kg·d). After modeling or treatment, the value of E/A and E/e' in each group of rats were measured by echocardiography. The N-terminal pro b-type natriuretic peptide (NT-proBNP) level was determined by enzyme-linked immunosorbent assay (ELISA). Heart weight/body mass index (Hw/W) and left ventricular weight/body mass index (LVw/W) were calculated after the rats were sacrificed; the transforming growth factor-β1 (TGF-β1) protein expression level in cardiac tissue was detected by western blot., Results: Compared with sham group, the values of diastolic function item (E/A) and mitral annular early diastolic velocity (E/e') in HFpEF group were significantly decreased, and the level of NT-proBNP was significantly increased (P<0.05). Compared with HFpEF group, the value of E/A and E/e' in HF + I group were significantly increased, and the level of NT-proBNP was significantly decreased (P<0.05). Compared with sham group, the expression of TGF-β1 protein in heart tissue of HFpEF group were significantly increased (P<0.05). Compared with HFpEF group, the expression of TGF-β1 protein in HFpEF + I group were significantly decreased (P<0.05)., Conclusions: Kangdaxin oral liquid has protective effect on heart in HFpEF rats, which can reduce the protein expression of TGF-β1 in the heart tissue of HFpEF rats. This may be a possible mechanism to inhibit myocardial fibrosis and improve cardiac diastolic function., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-198/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: Glucagon-like peptide-1 (GLP-1) mimetics are widely used for treating type 2 diabetes (T2D) with pleiotropic effects on heart and kidneys. The safety/tolerability and pharmacokinetics/pharmacodynamics ((PK/PD) of CJC-1134-PC (a long-acting GLP-1) were investigated in Chinese., Method: Two randomized, double-blind, placebo-controlled phase I studies were conducted. Study A: 30 healthy subjects received (subcutaneously injected) a single dose (2 mg) or titrate doses (2 + 3 and 2 + 3 + 4 mg at weekly intervals) of CJC-1134-PC. Study B: 49 T2D subjects received 10 weekly doses (1, 2, 3, and 4 mg)., Result: CJC-1134-PC was well tolerated with gastrointestinal (GI) side effects. Higher doses increased the adverse events risk. CJC-1134-PC was steadily absorbed, with maximum plasma concentrations(C max ) occurring at 36-72 h and 48 h after administration in healthy and T2D subjects, respectively. The steady-state exposures in T2D subjects increased more than the dose-proportionality(1-3 mg). The mean t 1/2 ranged from 111.6 to 127.6 h. After four- five weeks of targeting doses, steady state was reached in T2D subjects with apparent accumulation effect. At week 11 for T2D subjects, HbA1c mean baseline change was significantly different than that of the placebo, and the fasting plasma glucose (FPG) was not significantly altered., Conclusion: The safety and PK/PD profiles of weekly CJC-1134-PC doses support Phase II studies with guidance on optimal-dose selection. Clinical trial registration: ChiCTR-IPC-15007190.

Objective: Recombinant human albumin (rHA) is an alternative to human serum albumin (HSA) for treating ascites in cirrhosis patients. This study was to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics/pharmacodynamics (PK/PD) of rHA in healthy subjects to guide the design for further clinical trials., Methods: Healthy subjects aged 18-55 years were enrolled in this double-blinded, first-in-human, placebo-controlled single ascending dose (SAD) (1.25, 5, 10, 20, or 30g) and positive-controlled multiple-dose study (3-day treatment of 10g/day for three cycles every three weeks). The safety was assessed by adverse events (AEs). Antibodies (IgE and IgD) and cytokines were analyzed for immunogenicity. Serum albumin levels and changes in plasma colloid osmotic pressure (PCOP) and hematocrit (HCT) were measured for PK/PD analysis., Results: rHA was well tolerated as all AEs were assessed as mild or moderate. No severe allergy or difference in the incidence of AEs was observed among the different cohorts in the SAD study or in the different cycles in the multiple-dose study. The incidence of AEs was similar for the rHA and HSA cohort. Antibodies or cytokines showed no changes after drug administration. As expected, serum albumin levels and PCOP increases, and HCT ratio decreases were dose-related with significant differences (p < 0.01). No differences were observed between rHA and HSA., Conclusion: rHA is safe and well-tolerated in healthy Chinese subjects. rHA and HSA exhibited similar safety, tolerability, and PK/PD profiles. The results support further evaluation of rHA treatment in cirrhotic patients with ascites. The clinical trial registration numbers are CTR20191221 (http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml)., (Copyright © 2021. Published by Elsevier B.V.)

Hepatitis B virus capsid assembly modulators (HBV CAMs) are promising, clinically validated therapeutic agents for the treatment of chronic hepatitis B (CHB). The safety, tolerability, and pharmacokinetic (PK) profiles of GST-HG141, a novel HBV CAM, were evaluated in healthy Chinese volunteers. This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 300, 400, or 500 mg) study comprising a food-effect investigation (300 mg) and a multiple-ascending-dose (MAD) (100 or 200 mg twice daily) study. GST-HG141 reached the maximum plasma concentration ( C max ) at 1.25 to 3.00 h (median T max ). The exposure exhibited a linear increase, while the mean half-life ( t 1/2 ) ranged from 13.096 h to 22.121 h. The exposure of GST-HG141 (300 mg) was higher after food intake by about 2.4-fold. In the MAD study, steady state was reached at around day 5, and the mean trough steady-state concentrations were 423 and 588 ng/ml for 50- and 100-mg cohorts, respectively. The ratios of GST-HG141 accumulation were <1.5. GST-HG141 was well tolerated in healthy Chinese subjects. The rates of adverse events in the GST-HG141 cohort did not differ from those of the placebo cohort. GST-HG141 was tolerated in healthy Chinese subjects. The safety and PK profiles of GST-HG141 support the further evaluation of its efficacy in individuals with CHB. (This study has been registered in ClinicalTrials.gov under identifier NCT04536337.).

Background: Felbinac trometamol, an anti-inflammatory and analgesic drug, has been used to treat immediate postoperative pain., Objective: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of single or multiple intravenous infusions of felbinac trometamol in healthy Chinese volunteers., Methods: A total of 56 healthy subjects were enrolled in a single-ascending dose study (11.78-377.00 mg), meanwhile 36 subjects were enrolled in a multiple-ascending dose study (47.13-188.50 mg). Safety endpoints included treatment-emergent adverse events, vital signs, electrocardiograms, and laboratory parameters. Pharmacokinetic endpoints included exposure of subjects to felblinac and metabolites of the drug in plasma, urine, and feces., Results: Felblinac time to maximum plasma concentration was obtained at 0.5 h, corresponding to the end of the infusion. Maximum plasma concentration and area under the curve increased in a dose-dependent manner for felblinac and its metabolite, showing linear pharmacokinetic characteristics at single and multiple doses. After intravenous infusions of multiple doses three times (30 min each time) per day, the accumulation ratio of felblinac and its metabolite based on the area under the curve had a range of 1.34-1.45 and 1.60-1.87, respectively, across cohorts. After administration of the fourth dose, the plasma concentration of both felblinac and its metabolites was maintained at a steady state. Felbinac trometamol was well tolerated. Neither treatment-emergent adverse event frequency nor severity increased with increasing felbinac trometamol dose., Conclusions: Felbinac trometamol was well tolerated in our study. Based on the dose range in this study, 94.25 mg is the recommended target dose for a phase II study., Clinical Trial Registration: CTR20170496 and CTR20180896. The dates of registration are 2017-06-19 and 2018-07-02 ( https://www.chinadrugtrials.org.cn/ ).

Purpose: Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir have been approved worldwide for the treatment of chronic hepatitis C virus (HCV) infection. Although both have been approved in China, there are currently no data on their pharmacokinetic profiles in Chinese individuals. Two studies investigated the pharmacokinetic properties, safety, and tolerability of ledipasvir/sofosbuvir and sofosbuvir/velpatasvir, respectively, in healthy Chinese subjects., Methods: Two Phase I, open-label, single- and multiple-dose studies were conducted in healthy Chinese subjects. Ledipasvir/sofosbuvir (90/400 mg) or sofosbuvir/velpatasvir (400/100 mg), respectively, was administered orally once daily under fasted conditions. Subjects received a single dose (day 1) and multiple doses (days 8-17 [ledipasvir/sofosbuvir]; days 8-14 [sofosbuvir/velpatasvir]). Plasma pharmacokinetic parameters were estimated by using noncompartmental models, and safety was assessed through clinical evaluation and monitoring of adverse events., Findings: Fourteen subjects were enrolled in each study (7 men, 7 women each; mean age, 30 years [ledipasvir/sofosbuvir] and 29 years [sofosbuvir/velpatasvir]). The pharmacokinetic parameters for sofosbuvir, GS-566500, GS-331007, and ledipasvir or velpatasvir were similar to historical values in non-Chinese subjects. Consistent with the t 1/2 of ledipasvir relative to 24-h dosing, accumulation of 177% (AUC) and 107% (C max ) was observed. There was no significant accumulation of velpatasvir, sofosbuvir, GS-566500, or GS-331007. Both drugs were generally well tolerated; no serious adverse events or discontinuations due to adverse events were reported., Implications: Overall, ledipasvir/sofosbuvir and sofosbuvir/velpatasvir exhibited pharmacokinetic and safety profiles in healthy Chinese subjects similar to those in non-Chinese subjects in historical studies, supporting their use in the Chinese population with HCV infection. ChinaDrugTrials.org.cn identifiers: CTR20160149 (ledipasvir/sofosbuvir); CTR20160602 (sofosbuvir/velpatasvir)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Iron deficiency (ID) is one of the most commonly known nutritional deficiencies and is considered the primary cause of anemia (iron-deficiency anemia). Ferric carboxymaltose (FCM), an intravenous iron preparation, has been widely used for >10 years for iron-deficiency anemia treatment worldwide because of its many advantages., Methods: This single-center, open-label, single dose escalation study in Chinese subjects was designed to assess the pharmacokinetic/pharmacodynamic parameters and safety of FCM in this population. The first 12 subjects received a 500-mg dose; after assessing safety data from the first 6 subjects in this cohort, another 12 subjects were assigned to the 1000-mg dose cohort., Findings: After an infusion of FCM over 15 min, a rapid dose-dependent increase in total serum iron levels was observed with a median T max of 30 min following the start of the infusion for both cohorts. The C max and AUC for the 1000-mg dose were ~1.8-fold (p = 0.2929) and 2.3-fold (p = 0.0318) those associated with the 500-mg dose, respectively. Mean terminal t 1/2 values were 12.3 and 10.5 h for the 2 cohorts. The renal elimination of FCM was negligible (<0.1%). Increase in mean serum iron levels and ferritin concentrations showed dose dependency. Iron-binding capacity was transiently well utilized after dosing, as indicated by transferrin saturation >88% with 500-mg FCM and >90% with 1000-mg FCM. Hemoglobin levels did not show significant changes during the 7-day observation period, whereas mean reticulocyte counts significantly increased in both cohorts, suggesting activation of the hematopoietic system. FCM was well tolerated in these Chinese subjects. No new or unexpected treatment-emergent adverse events were attributable to FCM., Implications: The pharmacokinetic/pharmacodynamic and safety profiles in Chinese subjects seemed comparable to those in white and Japanese populations. ChinaDrugTrials.org.cn identifier: CTR20160863., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to explore the tolerance, variability, and pharmacokinetics (PK) of bevacizumab biosimilars (MIL60, BAT1706, IBI305) in Chinese healthy male subjects., Methods: This randomized, double-blind, two-arm, parallel studies included three separate investigations, which were conducted by three sponsors to investigate the bioequivalence of bevacizumab biosimilars (MIL60, BAT1706, IBI305) with that of bevacizumab-EU as a reference drug. Subjects received a single-dose of 1 or 3 mg/kg of the bevacizumab biosimilars or bevacizumab-EU and were followed up for 70-99 days. Serum concentrations of bevacizumab, antidrug antibody (ADA), and neutralizing antibody (NAb) were measured using electrochemiluminescence. In addition, the PK parameters were determined using non-compartmental methods. The safety assessments included adverse events, hematology tests, and biochemistry tests., Results: The three bevacizumab biosimilars exhibited similar PK properties to that of bevacizumab-EU. Bevacizumab demonstrated linear PK properties and a concentration-dependent disposition. When comparing the three biosimilars with bevacizumab-EU, the 90% CIs of the ratios for C max , AUC 0-t , and AUC 0-∞ were within 80-125%. The inter-CV ranged from 12.6 to 23.3%. Three subjects in the biosimilar groups and bevacizumab-EU were positive for the ADA and negative for the NAb. Treatment-related mild or moderate adverse events were reported in 56-80 and 36-80% of subjects in the biosimilar and bevacizumab treatment arms, respectively., Conclusions: The bevacizumab biosimilars exhibit similar PK characteristics to that of the reference product bevacizumab-EU. The inter-CV is moderate and less than 25% in all cases. The safety profile was similar among bevacizumab biosimilars and bevacizumab-EU with significant adverse events.

Background: Pradefovir is efficiently converted to adefovir [9-(2-phosphonylmethoxyethyl) adenine (PMEA)], producing high hepatic PMEA concentration but low levels in the systemic circulation and kidney. The aim of this study is to evaluate the tolerability, adverse effect (AEs), pharmacokinetics and pharmacogenetics of a single ascending dose of pradefovir., Methods: Fifty healthy subjects were divided into five groups and randomized within each group at a ratio of 3:1:1 to receive a single ascending dose of pradefovir (10, 30, 60, 90, or 120 mg), and 10 mg adefovir dipivoxil (ADP) or placebo. Blood and urine samples were collected and analyzed. A total of 1930 polymorphic loci were analyzed in 6 blood samples collected from the 90 mg pradefovir group., Results: The single oral dose of pradefovir up to 120 mg was well tolerated. A total of 29 dose-limited mild AEs were reported in 17 subjects. The peak plasma concentration (C max ) and area under the curve (AUC) 0-48 of serum pradefovir ranged from (21.41 ± 12.98) to (447.33 ± 79.34) ng/mL and (46.10 ± 29.45) to (748.18 ± 134.15) ng h/mL across the dose range, respectively. The C max and AUC 0-48 of serum PMEA ranged from 18.10 ± 4.96 to 312.33 ± 114.19 ng/mL and 72.65 ± 28.25 to 1095.48 ± 248.47 ng h/mL. Generally, no kidney impairment was observed. Pharmacogenetic analysis identified three metabolism-related single nucleotide polymorphism (SNP) locis, P450 (cytochrome) oxidoreductase [POR (rs6965343)], arylamine N-acetyltransferases [NAT1 (rs4986993)] and CYP2F1 (rs305968)], and one distribution-related loci, orosomucoid 2 [ORM2 (rs12685968)]., Conclusions: The single oral dose of pradefovir 10-120 mg was well tolerated. SNPs may be associated with variable rates of adverse events., Trial Registration Number: CTR20140341.

In situ gelling thermosensitive hydrogel formulation has been reported to effectively sustain the release of macromolecules for a long time. However, the low-molecular-weight hydrophilic drugs, such as doxorubicin (DOX), are not suitable for intratumoral injection because the release will complete within one day. In this study, liposomal doxorubicin (LipDOX) was added into the hydrogel to form a novel thermosensitive formulation which prolonged the sustained release of DOX. DOX+C/GP (doxorubicin in chitosan/β-glycerophosphate) was prepared to compare with LipDOX+C/GP (liposomal doxorubicin in chitosan/β-glycerophosphate hydrogel). The particle size of DOX-loaded liposome was 94.2nm and the encapsulation efficiency of DOX was near 98%. In vitro release experiments, the release of DOX in both DOX+C/GP group and LipDOX+C/GP group increased along with the increasing pH of buffers. However, the LipDOX+C/GP group with lower initial burst release had a much longer releasing duration than DOX+C/GP group (21days vs. 24h). In vitro and in vivo antitumor experiments demonstrated that LipDOX+C/GP group had better antineoplastic effect and less toxicity than DOX+C/GP group. Pharmacokinetics study showed LipDOX+C/GP exhibited a higher AUC0-t and longer MRT than DOX+C/GP in blood and tumor, which indicated that LipDOX+C/GP obtained an enhanced antitumor activity compared with DOX+C/GP. In addition, the lower distribution index (the ratio of AUC of normal tissue/AUC of tumor tissue) of the LipDOX+C/GP implied it had lower toxicity to normal tissues than DOX+C/GP. Therefore, the novel thermosensitive hydrogel formulation was potential for clinical application in cancer treatment., (Copyright © 2016. Published by Elsevier B.V.)

The antitumor pharmacological property of flavonoids is correlated with inhibition towards glyoxalase I (GLOI), a critical zinc-enzyme in the methylglyoxal detoxification pathway. In this study, 16 flavonoids were examined, and only baicalein (Ki of 0.183 µM) is identified as a potent in vitro GLOI inhibitor. X-ray crystallographic analysis reveals that baicalein chelates with the catalytic Zn(2+) via its characteristic C6/C7 hydroxyl groups. The coordination ability of flavonoids, and therefore their ability to inhibit GLOI, is determined by the Zn(2+) coordination geometry, the rigid skeleton of flavonoids and the geometry of the hydrophobic cavity of the GLOI active site. This structural basis could be useful in predicting GLOI inhibition of other natural polyphenols.

The compound series of traditional anticholinergics [atropine (Atr), anisodamine (Ani), anisodine (AT3), and scopolamine (Sco)], naturally occurring belladonna alkaloid, have been approved for numerous therapeutic uses since 1970s. Tiotropium, a novel M receptor antagonist for the treatment of chronic obstructive pulmonary disease, was structurally modified based on atropine-like drugs. Clinical phenomena suggested that the changes of substituent group were related to the pharmacokinetic and pharmacodynamic characteristics of the agents. In an attempt to compare the pharmacokinetics of the series of anticholinergics and investigate the subsets motivating selective anticholinergic potencies, a sensitive LC-MS/MS method was established to analyze the differences of pharmacokinetic parameters. In this paper, we determined the pharmacokinetics of atropine, anisodamine, anisodine, scopolamine, and tiotropium after i.v. and i.g. single dose administration. After i.v. administration, the maximum drug plasma concentrations (C max) of Atr, Ani, AT3, and Sco were 274.25 ± 53.66, 267.50 ± 33.16, 340.50 ± 44.52, and 483.75 ± 78.13 ng/mL. Tiotropium had a slightly higher area under the curve with a significant increase of C max value. Because of their partial solubility, Atr, Ani, AT3, and Sco had different bioavailability in rats of 21.62, 10.78, 80.45 and 2.52 %, respectively. Following i.g. administration of tiotropium, the C max value below 20 ng/mL revealed the very low oral absorption. The urinary excretion rates of Atr, Ani, AT3, Sco and tiotropium were 11.33, 54.86, 32.67, 8.69 and 73.91 %. This work provided relatively comprehensive preclinical data on the series of anticholinergics, which may be used to explain the clinical adverse effects and applications.

Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.

Iron is a challenging element due to its high background in various matrixes including blood, tissues even in the air and it is urgent to develop a method for the accurate determination of iron in bio-samples. After optimization of mass spectrometric conditions using collision cell technology and compensating for interference using a mathematical correction equation, an inductively coupled plasma mass spectrometry (ICP-MS) method for the quantitative determination of (58)Fe originating from hemin extrinsically labeled avoiding endogenous interference was developed. After a single step of dilution, analysis of each sample was completed within 1.5min. The assay was linear in the concentration range from 0.005 to 1.0μg/ml. The precisions and accuracies determined within three consecutive days were in acceptable limits and there was no significant matrix effect. The optimized method was successfully applied to a pharmacokinetic study of (58)Fe originating from hemin extrinsically labeled and iron absorption measured in rats was 1.07%. Those indicated that extrinsically label techniques in combination with ICP-MS will become a new tool for the analysis of iron preparations and other endogenous substances., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Carbon nanotube (CNT)-organic polymer hybrids have important potential applications in the immobilization of therapeutic biomolecules. Recently developed CNT-organic polymer composites require the use of organic solvents for their preparation and have limited polymer functionalization. To address these limitations, multi-walled CNT (MWCNT)-chitosan nanoparticle (CS NP) hybrids have been synthesized in situ by an ionotropic gelation process, which is extremely mild and involves the mixture of two aqueous solutions at room temperature. The MWCNT-CS NP hybrids were characterized by atomic force microscopy and thermogravimetric analysis. Under optimal conditions the CS NP can be tethered to the MWCNT surface in high density and with relatively uniform coverage. The MWCNT-CS NP hybrids show good dispersibility and stability in aqueous solutions. In order to evaluate the potential utilization of the hybrids as protein carries the cytotoxicity to HeLa cells and protein immobilization (of bovine serum albumin (BSA), used here as a model) capacity of the hybrids were investigated in detail. The results demonstrate that the MWCNT-CS NP hybrids are biocompatible at concentrations up to 100 μg mL(-1) for 24 h incubation. The MWCNT-CS NP hybrids improve the BSA immobilization efficiency 0.8 times and simultaneously decrease the cellular toxicity by about 50% compared with carboxylated MWCNT., (Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)