mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

mRNA therapy is an emerging treatment that has become a frontier and hot topic in the field of biomedicine.To explore the trend in the development of mRNA therapy,this paper conducts an analysis from the perspectives of papers and patents,examining multiple dimensions including development trend,research areas,and high-value research.The study reveals the following findings:Global research in mRNA therapy is growing rapidly.Basic research mainly focuses on oncology,chemistry-multidisciplinary,biochemistry and molecular biology,while applied research centers on mRNA concerning genetic engineering,isolation,synthesis,purification,and the development of medicines.High-value research mainly centers on topics such as mRNA delivery,composition,manufacture,modification,and the development of various mRNA-based therapies.

This study was aimed at surveying the distribution of Himalayan marmots in Gaotai County,Zhangye City,Gan-su Province,and analyzing the risk of plague occurrence,to provide a scientific basis for plague prevention and control in the area.On the basis of preliminary evidence,we used a combined approach of on-site investigation and Global Positioning System(GPS)positioning to survey the distribution and natural geographical landscape characteristics of the Himalayan marmot in Gaotai County.Population information and customs in the marmot distribution area were investigated through methods such as data retrieval and household visits.Himalayan marmots were captured through bow-shaped trapping,and blood,liver,spleen,heart,lung,kidney,femur,and surface-intermediate host samples were collected.Pathological and serological tests were conducted according to the Plague Diagnosis Criteria(WS279-2008).In Xinba Town,Gaotai County,Himalayan marmots were found in 16 villages(53.33％).Heping Village had the largest distribution area(100％),and was followed by Zhaoyi Village(79.17％)and Xishang Village(55.32％),whereas the other areas had values below 50％.Regarding the direct threats posed by marmots,Heping Village,Dongda Vil-lage,and Zhaoyi Village had values of 100％,Xishang Village had a value of 90.59％,and the other areas had values below 50％.The flea infestation rate on marmots'bodies was 59.62％,and the flea index was 1.48％(77/52).The main surface-in-termediate hosts were steppe ticks,body lice,Xenopsylla siberica,and Nosopsyllus laeviceps,accounting for 72.31％(517/715),16.92％(121/715),6.43％(46/715),and 4.20％(30/715),respectively,with steppe ticks being the dominant species.A total of 52 liver and spleen tissue samples from marmots,and 715 surface-intermediate hosts samples,were collected for bacterial culture.No Yersinia pestis was found.RIHA testing for plague F1 antigen was negative in all samples.Additionally,52 blood serum samples from marmots were collected,and IHA testing for plague-specific F1 antibodies was negative in all samples.The natural plague foci of marmots in the Qilian Mountains and Altyn Mountains is affected by factors including con-tinuing increases in temperature and grassland degradation.As a result,the marmot plague hosts continually migrate to sur-rounding non-epidemic areas,particularly in Gaotai County,Zhangye City.Local residents often hunt wild rabbits and mar-mots,thus posing a risk of human plague outbreaks if animal plague occurs.This county is recommended to be included in the province's plague surveillance and epidemic source investigation.Additionally,efforts should be strengthened in health educa-tion,medical personnel training,and management of key individuals and emergency reserves.If necessary,protective measures should be taken in marmot and flea control,to prevent the occurrence and spread of plague.

This study was aimed at surveying the distribution of Himalayan marmots in Gaotai County,Zhangye City,Gan-su Province,and analyzing the risk of plague occurrence,to provide a scientific basis for plague prevention and control in the area.On the basis of preliminary evidence,we used a combined approach of on-site investigation and Global Positioning System(GPS)positioning to survey the distribution and natural geographical landscape characteristics of the Himalayan marmot in Gaotai County.Population information and customs in the marmot distribution area were investigated through methods such as data retrieval and household visits.Himalayan marmots were captured through bow-shaped trapping,and blood,liver,spleen,heart,lung,kidney,femur,and surface-intermediate host samples were collected.Pathological and serological tests were conducted according to the Plague Diagnosis Criteria(WS279-2008).In Xinba Town,Gaotai County,Himalayan marmots were found in 16 villages(53.33％).Heping Village had the largest distribution area(100％),and was followed by Zhaoyi Village(79.17％)and Xishang Village(55.32％),whereas the other areas had values below 50％.Regarding the direct threats posed by marmots,Heping Village,Dongda Vil-lage,and Zhaoyi Village had values of 100％,Xishang Village had a value of 90.59％,and the other areas had values below 50％.The flea infestation rate on marmots'bodies was 59.62％,and the flea index was 1.48％(77/52).The main surface-in-termediate hosts were steppe ticks,body lice,Xenopsylla siberica,and Nosopsyllus laeviceps,accounting for 72.31％(517/715),16.92％(121/715),6.43％(46/715),and 4.20％(30/715),respectively,with steppe ticks being the dominant species.A total of 52 liver and spleen tissue samples from marmots,and 715 surface-intermediate hosts samples,were collected for bacterial culture.No Yersinia pestis was found.RIHA testing for plague F1 antigen was negative in all samples.Additionally,52 blood serum samples from marmots were collected,and IHA testing for plague-specific F1 antibodies was negative in all samples.The natural plague foci of marmots in the Qilian Mountains and Altyn Mountains is affected by factors including con-tinuing increases in temperature and grassland degradation.As a result,the marmot plague hosts continually migrate to sur-rounding non-epidemic areas,particularly in Gaotai County,Zhangye City.Local residents often hunt wild rabbits and mar-mots,thus posing a risk of human plague outbreaks if animal plague occurs.This county is recommended to be included in the province's plague surveillance and epidemic source investigation.Additionally,efforts should be strengthened in health educa-tion,medical personnel training,and management of key individuals and emergency reserves.If necessary,protective measures should be taken in marmot and flea control,to prevent the occurrence and spread of plague.

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.
Humans ; Electroacupuncture ; Ischemic Stroke ; Learning ; Signal Transduction/physiology*

The study aims to explore the effects and mechanisms of water extract of Potentilla anserina (PA) on myelosuppression mice induced by cyclophosphamide based on metabonomics. The myelosuppressive mouse model was established by injected with cyclophosphamide and treated with water extract of PA. Thymus and spleen indexes, peripheral hemogram and bone marrow nucleated cells of each group was detected. Bone marrow pathology analysis was performed by hematoxylin-eosin staining. The levels of interleukin 3 (IL-3), interleukin 6 (IL-6), erythropoietin (EPO), granulocyte colony stimulating factor (GM-CSF), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were measured. The changes of biomarkers and related metabolic pathways were analyzed by UPLC-Q-TOF/MS-based metabonomics. Animal experiments were approved by the Animal Ethics Committee of Southwest Minzu University. The high doses of PA could significantly improve the decrease of white blood cell (WBC), red blood cell (RBC) counts and hemoglobin (HGB) levels of mice induced by cyclophosphamide (P < 0.05), and significantly increase the number of nucleated cells and the area of hematopoietic tissue in femoral bone marrow. The medium and high doses of PA could significantly improve the serum levels of SOD, CAT, MDA, IL-6 and GM-CSF (P < 0.05), and have no significant effect on the expression of IL-3 and EPO (P > 0.05). Serum metabolomics analysis showed that the aqueous extracts of PA could alleviate myrosuppression by regulating the aminoacyl-tRNA, valine, leucine and isoleucine biosynthesis mediated by 13 different metabolites such as valine, leucine, asparagine and hydroxyisohexic acid. PA improve the inhibition of hematopoietic function in myelosuppression mouse, and its mechanisms may be related to anti-oxidation and promoting the expression of hematopoietic-related cytokines and regulating the related metabolic pathways.

Heart Valve Diseases ; Heart Valve Prosthesis ; Humans ; Hypereosinophilic Syndrome/complications* ; Mitral Valve ; Thrombosis/etiology*

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)₃ gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)₃ gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.