Latest ArticlesTo explore the standardization of the in vitro Nb2-11 cell proliferation bioassay for recombinant human growth hormone (rhGH), we first tested the biological activity of 2 batches of rhGH drug substances, 3 batches of rhGH for injection, and 24 batches of rhGH injections, based on which we proposed the experimental effective criteria. Furthermore, we conducted methodological validation in accordance with General Rule 9401 of the 2020 edition of the Pharmacopoeia of the People's Republic of China. Subsequently, the inter-laboratory consistency, intra-laboratory and inter-laboratory precision of seven labs were studied by determining the in vitro bioactivity of six batches of rhGH products and two batches of rhGH drug substances from four different manufacturers using this method. The consistency of the in vitro and in vivo bioassays was assessed by evaluating 28 batches of rhGH drug substances with both methods. Finally, multiple batches of rhGH samples with different expiration dates were tested to determine the standard limits of the bioassay. The results of this collaborative study indicate that the Nb2-11 cell bioassay exhibits good intra- and inter-laboratory reproducibility, with a 100% pass rate for the experimental effective criteria. The Nb2-11 cell bioassay had high consistency with in vivo animal bioassay. Animal experiments were approved by the Experimental Animal Welfare Ethics Committee of China National Institute of Food and Drug Control (approval number: NIFDC (Fu) No. 2024 (B) 004). This method is applicable to rhGH drug substances and products from different manufacturers. Collectively, the Nb2-11 cell bioassay can be used as a standardized method for determining the biological activity of rhGH products, replacing in vivo animal methods for quality control and release testing.
A detection method using UHPLC-MS/MS was established for the determination of 53 prohibited veterinary drug residues in goat horns, including 16 tranquilizers, 14 β-agonists, chloramphenicol, 4 fluoroquinolones, 7 nitroimidazoles, 3 quinoxalines, and 8 other compounds. Samples were extracted using salting-out assisted liquid-liquid extraction (SALLE). A Zorbax Eclipse Plus C18 column (1.8 μm, 3.0 mm × 150 mm, Agilent) was used with 0.1% formic acid solution-acetonitrile as the mobile phase for gradient elution. Detection was performed in positive and negative electrospray ionization modes using multiple reaction monitoring (MRM). All 53 analytes showed good linearity within their respective concentration ranges, with correlation coefficients above 0.99. The average recoveries at three spiked levels ranged from 70.4% to 118.7%, with relative standard deviations (RSDs) ranging from 0.69% to 12.07%. The limits of detection (LODs) ranged from 0.1 to 50 μg·kg-1, and the limits of quantitation (LOQs) ranged from 0.2 to 100 μg·kg-1. This method has been applied to the determination of real samples.
The critical relative humidity (CRH) is an important indicator for measuring the hygroscopicity of solid drugs. The intrinsic mechanism of rapid moisture absorption of water-soluble drugs under CRH is not fully understood, and we conducted preliminary exploration on this topic. Firstly, the newly developed model tablet moisture absorption method and the traditional powder moisture absorption method were employed to determine the CRH values, an equivalence test between the two methods was conducted by a two-tailed t test. Then a conductivity meter was employed to measure the conductivity values of drug model tablets under different relative humidity (RH) conditions. As we know, anhydrous copper sulfate is a grayish white powder, which is easy to turn blue after absorbing water, based on this, this salt was selected as a model drug, and its CRH value was measured. Furthermore, anhydrous copper sulfate was compressed into tablets, then placed under different RH conditions. A series of photos were taken to record the formation process of the liquid film. The reason for the inflection point of the moisture absorption equilibrium curve was postulated based on changes in conductivity and color. The results showed that the CRH values of sucrose powders and tablets were 85.05% and 85.01%, respectively; and the CRH values of sodium citrate powders and tablets were 77.14% and 76.93% individually; the results of the two-tailed t test indicated that the two methods are equivalent. At RH of 75%, the conductivity of sodium citrate changed slightly, while at RH of 79% greater than the CRH, the conductivity underwent a sudden change. Sucrose and anhydrous copper sulfate showed a similar trend of change. In addition, the process of blue dots of anhydrous copper sulfate changing from discrete to continuous was successfully captured during the observation of moisture absorption. In summary, the aforementioned results suggest that the mechanism of the rising rapidly in moisture absorption curve of water-soluble drugs at CRH is probably attributed to the formation of a continuous aqueous "liquid film" on the drug surface during the process of moisture absorption.
To prepare a progesterone pressure-sensitive gel patch combined with a microneedle to enhance drug release, HPLC was used to determine the preparation's progesterone content. One-way and orthogonal experiments were used to optimize the patch's prescription. Adhesion, sensory evaluation, cumulative release, and cumulative penetration were used as evaluation indices. Three microneedles with varying needle heights were made using 3D printing, and the cumulative penetration of the patch and microneedles was calculated and compared with the patch alone. The orthogonal experiments showed that the optimal prescription for the patches was Duro-Tak 87-2677 pressure-sensitive adhesive (87.5%), tributyl citrate (2%), isopropyl myristate (5%), dibutylated hydroxytoluene (0.5%), and drug (5%). The patches were prepared according to the optimized prescription, resulting in good patch formability and adhesion. In the transdermal penetration test, the cumulative penetration of the patch was 52.35 ± 7.88 μg·cm-2 at 24 h, and the cumulative penetration of the patch in combination with 500, 750, and 1 000 μm microneedles was 226.01 ± 7.46, 278.78 ± 6.59, 422.95 ± 16.81 μg·cm-2, respectively. The experiment was approved by the Experimental Animal Ethics Committee of Xinjiang Medical University (IACUC-20220725-8). The optimal patch prescription was screened through one-way and orthogonal experiments, and the transdermal penetration effect of patch and microneedle combination preparation was better than that of single use, which can effectively increase the in vitro transdermal penetration of the drug, and the above study provides a theoretical basis for the application of transdermal patches of progesterone.
The HIV-1 capsid protein (CA) is an effective target for antiviral drug discovery. Targeting the capsid assembly inhibitor peptide (CAI) binding pocket in the C-terminal domain of HIV-1 CA (CA CTD) can be used to screen for CA protein inhibitors. In this study, we found that the small molecule suramin targets HIV-1 CA by binding to this pocket, with an IC50 value of 2.1 μmol·L-1 for inhibiting the CA CTD-CAI interaction, based on homogeneous time-resolved fluorescence (HTRF) technology. Bio-layer interferometry (BLI) experiments demonstrated that suramin binds directly to CA, with a binding affinity to CA hexamer (KD = 248 nmol·L-1) higher than to CA monomer (KD = 227 μmol·L-1). In addition, in vitro CA protein assembly assays showed that suramin promotes disordered multimerization of CA protein. Binding model analysis revealed that suramin binds to the interface between adjacent CA monomers in the CA hexamer through the N57, Q63, Q67 and Y169 residues, thereby enhancing CA multimerization. In summary, suramin is a CA protein inhibitor that targets the CA hexamer and can serve as a starting point for the discovery of new CA inhibitors.
Root rot represents a significant disease affecting the cultivation of Platycodon grandiflorum. The screening of biocontrol strains with antagonistic properties against this disease can provide valuable microbial resources for the environmentally friendly prevention and control of Platycodon grandiflorum diseases. In this investigation, high-throughput bacterial isolation techniques were utilized to isolate and purify endophytic bacteria from the roots of Platycodon grandiflorum. An antagonistic bacterial strain R34B7, was identified through the plate confrontation culture method, exhibiting a notable inhibitory rate of 52.18% against the pathogen causing root rot. Morphological characteristics, physiological and biochemical properties, and molecular identification results collectively confirmed that the antagonistic endophytic bacterium R34B7 belonged to the species Serratia plymuthica. The control efficacy of strain R34B7 against Platycodon grandiflorum root rot was assessed using tissue-cultured seedlings of Platycodon grandiflorum, revealing a disease control efficacy of 44.44%. Furthermore, the fermented supernatant of strain R34B7 demonstrated considerable inhibitory effects on both the mycelial growth and spore germination of the pathogen. By examining the extracellular hydrolytic enzymes and growth-promoting factors of strain R34B7, it was discovered that this strain possesses the abilities to produce protease, chitinase, fix nitrogen, solubilize phosphorus, synthesize siderophores, and produce indole-3-acetic acid, indicating its potential for growth promotion. The antagonistic bacterium R34B7 identified in this study exhibits promising biocontrol activity against root rot and holds considerable potential for further development and utilization.
New drugs approved by authorities are classified into two categories: new molecular entities (NME) and fixed dose combination (FDC) formulations, both of which are documented by scientific experiments and clinical trials. Complex diseases frequently possess multifactorial causes, and drugs that only focus on a single target may not achieve satisfactory results; moreover, it is difficult to achieve full optimization of the pharmacodynamics, pharmacokinetics, safety, and patient compliance for a drug. Therefore, combinatorial remedies with two (or more) drugs at a fixed dose may provide patients with better treatment options. Based upon understanding the various molecular regulation of pathological processes and principles of drug action, clinicians and pharmacologists are able to design new FDC to achieve optimum efficiency in clinical practice. In this sense the significance of FDC is no less than NME, because it is closer to clinical practice and directly meets the needs of patients. This article briefly analyzes the development of FDC from the microscopic characteristics of pathology and the molecular mechanism of drug action with influential examples.
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
As the biggest tissue of human body, skin is the first barrier of resisting external aggression. Collagen is one of important parts of the skin, which could not only affect the aesthetics of skin, but also influence the health and normal function of skin. It is the great significance to find ways that could inhibit the loss of collagen. The mechanisms of the collagen degradation in skin are complex and multifaceted. Natural bioactive products have unique advantages in treating the loss of collagen, which have multi-targets and mechanisms. In this review, the mechanisms of skin collagen degradation are discussed, and the research progress of natural bioactive products in resisting skin aging through promoting collagen synthesis are reviewed, in order to provide references for futural research.
Functional disorders of the Golgi apparatus are harmful to the health of organisms, leading to various diseases. Removing damaged Golgi apparatus is crucial for maintaining cellular homeostasis, therefore, autophagy of Golgi apparatus has gradually attracted attention. This article summarizes Golgi autophagy, briefly describes its structure and functions, Golgi autophagy receptors, and the role of Golgi autophagy in disease treatment. It also proposes the new concept of Golgimedicine, which looks forward to the role of Golgi in disease diagnosis, treatment, prognosis, genetic diseases, and rare diseases. This article aims to explore the scientific connotations of Golgi autophagy, Golgi structure and function from the perspective of Golgimedicine, providing theoretical references for drug target research, new drug development, and the healthy development of humanity.
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