Because of the characters of effective, safe and easy to be produced on a large scale, mRNA drugs have showed great potential on preventing viral infections. mRNA represents an emerging field of precision medicine, several mRNA drugs targeted therapies for infectious diseases and cancer have shown beneficial results both in vivo and in vitro. mRNA is stable, immunogenic, and not limited by the receptor's major histocompatibility complex (MHC) type. In theory, mRNA can achieve in vivo expression of different target proteins, which makes the development of mRNA drugs more flexible and can be used to prevent and treat many refractory or hereditary diseases. This paper introduced the primary structure and higher structure of mRNA, and summarized the progress of mRNA drugs in clinical application, which was expected to help understand the drug function of mRNA, and the clinical application, and provide the direction for the development of mRNA drugs.
Norovirus (NoV) is one of the main pathogens causing acute gastroenteritis. NoV is prone to mutating and producing multiple strains that pose a significant threat to human health. Subsequent evaluation of anti-NoV drugs and vaccines is limited by the lack of successful animal models, and no vaccines are currently on the market for NoV prevention. In this paper, the research progress of NoV vaccine was reviewed, focusing on the research status and development prospects of virus-like particle (VLP) vaccine, viral vector vaccine and P-particle based vaccine, in order to provide new ideas for NoV vaccine research and development.
Respiratory syncytial virus (RSV) is a leading cause of respiratory and lung infections, especially in young children and the elderly, which are prone to serious infections. Despite the global impact of RSV infection on healthcare, the current therapy is still mostly supportive. Over the past few decades, our understanding of the pathogenesis and immunopathology of RSV had evolved, leading to significant advances in RSV prevention strategies. More than 50 years have passed since the RSV vaccine was first trialed in 1966, and two RSV vaccines have been approved. In this paper, current treatment options for RSV infection (including RSV-specific and non-specific) and the development progress of different RSV prevention vaccines were reviewed, which was expected to provide reference for the treatment and vaccines research and development of RSV.
Immunoglobulin Y (IgY), as a potential therapeutic antibody, is present in many species, from lower amphibians and reptiles to higher animal birds. The development of vaccines has become a competitive arena for global scientists to compete against viruses. Although the vaccine can effectively prevent the infection of the virus, reduce the incidence and mortality of the disease, but the development of the vaccine is time-consuming and costly. IgY has the advantages of easy production, low cost, take effect quickly, and antibody therapy strategies basedon IgY have been widely recognized in recent years. This review focused on the application of IgY in the treatment of viral diseases by reporting the latest research on the characteristics of IgY and the progress of production technology, so as to provide some enlightenment for the application of IgY in the treatment of viral infectious diseases.
Cervicitis is a kind of frequent gynecological disease, which brings trouble to more and more women. Antibiotics are often used in clinical treatment of cervicitis, which has great side effects. In this study, recombinant collagen was developed into a topical gynecological gel and applied to the treatment of cervicitis in rats. 25% phenol glue was used to induce cervicitis animal model in SD rats, and then recombinant collagen gynecological gel was injected into vagina by local administration for treatment. The changes of vulva swelling and purulent secretion in cervicitis model rats were observed. Hematoxylin-eosin(HE) and masson staining were used to examine the histopathologic changes and collagen deposition in rats. The expression levels of IL-6 protein and Ki-67 protein in the tissues were detected by immunohistochemical experiments. The regulation of inflammatory response and promoting cell proliferation were evaluated in the vaginal and cervical tissues of each group. Results showed that, compared with normal group, the body weight of rats in model group was significantly reduced (P<0.05). Vaginal opening was red, swollen, and purulent secretions flowed out (P<0.05). Cervical tissues showed cell degeneration, necrosis and exfoliation, and a large number of inflammatory cells infiltrated. The expression of IL-6 protein was significantly up-regulated (P<0.05), and the expression of Ki-67 was decreased (P<0.05). Compared with model group, the body weight of rats in positive control group, GG01 group and GG02 group was significantly increased after treatment(P<0.05). The swelling and secretions of the vaginal opening were significantly reduced (P<0.05), the inflammatory cell infiltration was significantly reduced, there was no obvious edema and congestion, collagen deposition and orderly arrangement were shown in the tissues, and the treatment effect of GG02 group was more significant. The expression levels of IL-6 and Ki-67 in GG02 group and positive control group were close to those in normal group, the inflammatory response was reduced, and the proliferation level of damaged tissue cells was restored. The recombinant collagen gynecological gel has a good therapeutic effect on acute cervicitis in rats and provides data support for its clinical application.
Due to the gradual destruction of the ozone layer, the amount of ultraviolet radiation is greatly increased, which would lead to chemical reactions in the skin of nucleic acids, proteins and other large molecules, resulting in skin erythema, pigmentation, sunburn, photoaging and even cancer. Taking recombinant human type Ⅲ collagen (rhCol Ⅲ) as the research object, the cytotoxicity of recombinant human type Ⅲ collagen on fibroblasts (L929) and its repairing effect on skin damaged by ultraviolet radiation in guinea pigs were investigated. The results showed that rhCol Ⅲ had no potential cytotoxicity to L929 cells in vitro. In vivo animal experiments have confirmed that rhCol Ⅲ had obvious repairing effect on the skin damaged by ultraviolet radiation phototoxicity in guinea pigs, which could reduce the skin wrinkles after skin injury, improved the epidermal hyperplasia of the injured skin tissue and the inflammation of the dermis. The expression of Vimentin and human melanoma monoclonal antibody 45 (HMB45) in injured skin were decreased. The above results indicated that rhCol Ⅲ had good safety in the repair treatment of the skin damaged by ultraviolet radiation in guinea pigs, rhCol Ⅲ could significantly improve the degree of epidermal layer thickening and keratinization of the skin of guinea pigs exposed to ultraviolet radiation, reduced the inflammatory response in the dermis and effectively regulate the degree of fibroblast fibrosisand the risk of melanoma. Results showed that, rhCol Ⅲ raw material has obvious therapeutic effect on skin damage caused by ultraviolet radiation.
Rheumatoid arthritis (RA) is a widespread systemic autoimmune disease characterized by joint immune dysfunction with severe synovitis and joint erosion, which can further lead to progressive disability. At present, the main therapeutic drugs for RA in clinical practice are disease modifying anti rheumatoid drugs (DMARDs) that alleviate the condition, including traditional synthetic DMARDs (csDMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). In addition, non steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs) are also included. Among them, bDMARDs and tsDMARDs have become the absolute mainstay of the RA market, but due to their long usage cycle and some safety issues, it is impossible to achieve effective and sustained relief, and the phenomenon of relapse often occurs after drug withdrawal, which further limits the clinical application. The article reviewed the research progress on the recurrence of major RA treatment drugs after discontinuation in clinical practice, in order to provide an effective theoretical basis and new ideas for the clinical drug cycle and method.
Viral nucleic acid and RNA of biological tissue samples are easy to be affected by external environment and easily degrade, resulting in serious deviations in experimental results. Taking viral nucleic acid and guinea pig skin tissue sample RNA as research objects, the protective effect of tissue protectant on viral load and RNA in guinea pig skin tissue sample after preservation of them at different temperatures and different times was explored. The results showed that after storage at 4 ℃ for 30 days (d), 25 ℃ for 7 d or 37 ℃ for 24 hours (h), the viral load stored in tissue protectants did not change significantly compared with the initial viral nucleic acid dose (P>0.05). After storage at 4 ℃ for 30 d, 25 ℃ for 7 d or 37 ℃ for 24 h, compared with liquid nitrogen storage group, both tissue protectant group and commercially available RNA later group could maintain the extraction amount and purity of sample RNA in guinea pig skin tissue, with no statistical significance (P>0.05). The results showed that the tissue protectant could be used as a storage solution for scientific research or clinical tissue samples. It was placed at 4 ℃, 25 ℃ and 37 ℃ for a certain time, without affecting the viral load of viral nucleic acid and the amount and purity of RNA extraction from guinea pig skin tissue samples, which made the sample preservation more convenient and efficient.
Lentiviral vectors have been widely used to transfer exogenous DNA into human cells to treat various genetic diseases. Lentiviral vectors can integrate into the host genome, but their integration sites are often unpredictable, which may increase the uncertainty of their therapeutic efficacy. With the wide application of gene and cell therapy, regulators have also issued a series of technical guidance documents to ensure the continuous safety of products. Integration site analysis (ISA) is a key tool for evaluating the biological safety of gene therapy vectors by characterizing their integration profiles, as well as for tracking transgenic cells. This review mainly described the technological evolution of integration sites for retroviruses, and the advantages and development trends of analysis methods. At the same time, strategies to reduce the random integration of viruses into the genome were also reviewed, in order to provide reference for the analysis and detection of lentiviral vector integration as a point of view and the safety evaluation of new drug clinical trials in cell therapy products.
As the rapid development of biotechnology, the role of vaccines in the prevention and control of infectious diseases becomes increasingly significant, and widespread immunization is crucial for global health. However, there are considerable challenges in improving vaccine coverage in low- and middle-income countries. Due to the inherent instability and poor thermal stability of liquid vaccines, the high cost of cold chain distribution restricts the dissemination and administration of vaccines in these regions, leading to ineffective control of certain infectious diseases in remote areas. To ensure the stability and effectiveness of vaccines, freeze-drying (FD) technology has become one of the key technologies in vaccine preparation and preservation. This paper provided a comprehensive and systematic review of the principles of freeze-drying technology, its influencing factors, the application of FD technology in different types of vaccines, and its future development trends, which aimed to provide useful information and insights for further research and industrialization of vaccines.
A gas chromatography-mass spectrometry (GC-MS) method was developed for the determination of methyl celecoxib sulfonate and ethyl celecoxib sulfonate residues in celecoxib APIs and their formulations. The two impurities were derivatised into iodomethane and iodoethane by sodium iodide derivatisation with headspace injection, and separated on a DB-624 capillary column (60 m×0.25 mm, 1.4 μm), with helium as the carrier gas and detected by mass spectrometry detector. Both methyl celecoxib sulfonate and ethyl celecoxib sulfonate showed good linearity in the concentration range of 10~500 ng·mL-1; the recoveries were in the range of 80.87%~106.52% with the RSDs less than 10%; and the limits of quantification (LOQs) were both 10 ng·mL-1. Methyl celecoxib sulfonate and ethyl celecoxib sulfonate impurities were not detected in any of the celecoxib samples. The method is simple and accurate, which can be used for the detection of genotoxic impurities of two sulfonate esters, methyl celecoxib sulfonate and ethyl celecoxib sulfonate, in celecoxib.
The amplification performance of biological detection reagents, especially the biological activity of enzyme reagents, plays a decisive role in the detection results of real-time quantitative PCR. It is crucial to adopt different preservation technologies to maintain the biological activity of detection reagents, achieve long-term stable preservation and non-cold chain transportation of biological detection reagents at room temperature, and ensure the stability, accuracy, specificity and sensitivity of detection results. This paper reviewed the research progress of four different preservation technologies, including vacuum freeze-drying technology, spray drying technology, vitrification freezing technology, and summarized the advantages and disadvantages in application, in order to provide a certain scientific basis for the follow-up related work.