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1.
Biol Pharm Bull ; 47(5): 978-987, 2024 May 18.
Article En | MEDLINE | ID: mdl-38631865

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/d. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.


Diet, High-Fat , Emodin , Fructose , Liver , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/etiology , Male , Emodin/pharmacology , Emodin/therapeutic use , Emodin/analogs & derivatives , Liver/drug effects , Liver/pathology , Liver/metabolism , Diet, High-Fat/adverse effects , Mice , Triglycerides/blood , Cholesterol/blood , Disease Models, Animal , Blood Glucose/drug effects
2.
Regen Med ; 19(2): 93-102, 2024 Feb.
Article En | MEDLINE | ID: mdl-38415316

Objective: This study aimed to explore the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating collagenase-induced Achilles tendinopathy. Methods: Achilles tendinopathy in rats at early or advanced stages was induced by injecting collagenase I into bilateral Achilles tendons. A total of 28 injured rats were injected with a hUC-MSC solution or normal saline into bilateral tendons twice and sampled after 4 weeks for histological staining, gene expression analysis, transmission electron microscope assay and biomechanical testing analysis. Results: The results revealed better histological performance and a larger collagen fiber diameter in the MSC group. mRNA expression of TNF-α, IL-1ß and MMP-3 was lower after MSC transplantation. Early MSC delivery promoted collagen I and TIMP-3 synthesis, and strengthened tendon toughness. Conclusion: hUC-MSCs demonstrated a therapeutic effect in treating collagenase-induced Achilles tendinopathy, particularly in the early stage of tendinopathy.


Achilles Tendon , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Tendinopathy , Humans , Rats , Animals , Tendinopathy/therapy , Achilles Tendon/metabolism , Achilles Tendon/pathology , Collagenases/adverse effects , Collagenases/metabolism , Collagen Type I/adverse effects , Collagen Type I/metabolism , Mesenchymal Stem Cells/metabolism , Umbilical Cord/metabolism , Mesenchymal Stem Cell Transplantation/methods
3.
ACS Omega ; 8(43): 40934-40943, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-37929090

Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (N-methyl-d-aspartate) receptor antagonist, exhibited neuroprotective effects against cognitive and emotional dysfunction in many disorders. We performed cecal ligation and puncture (CLP) inducing sepsis as the ideal animal model of SAE. CLP-induced septic mice were given a memantine treatment through intragastric administration. The novel object recognition test indicated that memantine significantly improved cognitive dysfunction in septic mice. The open field test revealed that the anxiety-like behaviors and locomotion ability of septic mice were relieved by memantine. The pole test further confirmed the protective effects of memantine against immobility. Memantine significantly inhibited the excessive glutamate production and improved impaired neurogenesis on first and seventh day after sepsis, accompanying with reducing proinflammatory cytokines production (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1ß), and IL-10) and microglia activation in the brain of SAE. In addition, memantine treatment also reducing sepsis-induced brain blood barrier disruption via inhibiting the expression of metalloproteinase-9 (MMP-9). In conclusion, memantine exerted neuro-protective effects against cognitive and emotional defects, which might be considered as a promising therapy for SAE.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(3): 274-277, 2023 Mar.
Article Zh | MEDLINE | ID: mdl-36916340

OBJECTIVE: To explore whether barium chloride (BaCl2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. METHODS: Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl2 pretreatment group, with 20 mice in each group. The BaCl2 pretreatment group was continuously injected with BaCl2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). RESULTS: Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (µg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (µg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). CONCLUSIONS: Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.


Acute Lung Injury , Respiratory Distress Syndrome , Mice , Male , Animals , Lipopolysaccharides , Tumor Necrosis Factor-alpha , Mice, Inbred C57BL , Lung
5.
J Burn Care Res ; 44(4): 860-868, 2023 07 05.
Article En | MEDLINE | ID: mdl-36591959

Pressure ulcer (PU) is a common type of chronic wound that is difficult to treat. Platelet-rich plasma (PRP) is rich in cytokines and growth factors, and it can be divided into two categories according to its leukocyte content: leukocyte-poor PRP (P-PRP) and leukocyte-rich PRP (L-PRP). PRP has been applied in a variety of wound treatments, due to its strong ability to promote repair. This study aims to investigate the therapeutic effects of PRP on PU and elucidate the role of leukocytes in the treatment process. Sprague-Dawley rats were used to establish PU models of ischemia-reperfusion injury by applying magnets externally. L-PRP, P-PRP, and saline were injected into the dermal wounds. Wound healing analysis and sampling were performed on days 3, 7, 11, and 15 after treatment. Histological examinations, real-time PCR, immunohistochemical examinations, and biomechanical assay were carried out on the wound samples. The PRP groups exhibited greater wound inflammatory response than the control group in the early stage but the response reduced rapidly as the wound healed. On days 7, 11, and 15, the PRP groups also yielded better wound healing rates and histological outcomes than the control group, with superior biomechanical properties observed on day 15. Among both PRP groups, the L-PRP group attained a higher wound healing rate than the P-PRP group on day 7, with greater significant early inflammatory responses, and more prominent angiogenesis. Therefore, PRP is proven to accelerate the healing of PU, with L-PRP being more effective in regulating inflammation and promoting angiogenesis than P-PRP.


Burns , Platelet-Rich Plasma , Pressure Ulcer , Rats , Animals , Wound Healing , Pressure Ulcer/therapy , Rats, Sprague-Dawley , Burns/therapy , Platelet-Rich Plasma/metabolism , Leukocytes/metabolism
6.
Gland Surg ; 12(12): 1705-1713, 2023 Dec 26.
Article En | MEDLINE | ID: mdl-38229845

Background: There is much debate on the optimal treatment approach of papillary thyroid carcinoma (PTC). Different guidelines base recommendations on various risk factors. While diagnosing the various risk factors is difficult due to the technical limitations, intraoperative frozen section (IFS) may be a feasible method. We aim to real-time evaluate the multiple risk factors, including lymph node metastasis (LNM), extrathyroidal extension (ETE), multifocality using IFS, and then identify a more effective surgical plan, which may help avoid the need for a second surgery and improve prognosis of patients. Methods: We retrospectively reviewed the medical records of 364 patients from January 1, 2021 to December 31, 2021. All the patients were initially recommended to undergo a hemithyroidectomy (HT) with isthmusectomy and ipsilateral central compartment neck dissection (CCND). IFS would be executed immediately. Further total thyroidectomies (TTs) would be performed if: (I) results of IFS showed >5 LNM, or (II) there are 1≤ LNM ≤5 but with ETE and/or multifocal carcinoma. The patients were divided and investigated according to the extent of surgery. Results: Based on the results of IFS, 72 patients underwent TT. The TT group displayed larger average tumor diameter, greater age, higher average body mass index (BMI), and elevated incidence of hypertension and hyperlipidemia compared to the HT group. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IFS were 77.61%, 100%, 100%, and 88.46%, respectively. Conclusions: IFS is a highly reliable procedure. Comprehensively evaluating central compartment LNM, ETE, and multifocal carcinoma through IFS helps identify a more reasonable surgical option under the current clinical consensus, which may thus help avoid the need for a second surgery.

7.
Stem Cells Int ; 2022: 7432665, 2022.
Article En | MEDLINE | ID: mdl-35547633

Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a refractory disease. The treatment options for ONFH, especially nonsurgical ones, merit further investigation. To evaluate the combinatorial therapeutic effects of platelet-rich plasma clot releasate (PRCR) and umbilical cord mesenchymal stem cells (UC-MSCs) on glucocorticoid-induced ONFH, a dexamethasone (DEX)-treated cell model and a high-dose methylprednisolone (MPS)-treated rat model were established. Cell counting kit-8 (CCK-8) assay was performed in vitro to determine the optimum dosage of PRCR for UC-MSC viability. The effects of PRCR, UC-MSCs, and PRCR + UC-MSCs on cell viability, apoptosis, migration, and differentiation capacities of DEX-treated bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cell (HUVECs) were explored via Transwell assays. Western blotting was conducted to evaluate the expression levels of RUNX2, VEGF, caspase-3, and Bcl-2 in the coculture systems. Ultrasound-guided intra-articular PRCR, UC-MSCs, and PRCR + UC-MSC injections were performed on the ONFH model rats. Microcomputed tomography, histological and immunohistochemical analyses, tartrate-resistant acid phosphatase (TRAP) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess the therapeutic effects of PRCR and UC-MSCs on bone loss and necrosis induced by high-dose MPS. Results of this study revealed that the in vitro application of PRCR, UC-MSCs, and PRCR + UC-MSCs reversed the impaired proliferation and migration capacities and resisted apoptosis of BMSCs and HUVECs induced by DEX. Moreover, the PRCR and UC-MSC application significantly improved the alkaline phosphatase (ALP) and alizarin red (ALR) staining of BMSCs and tube formation capacity of HUVECs and promoted the protein expression of RUNX2 in BMSCs and VEGF in HUVECs. Similarly, in the ONFH rat model, the intra-articular injection of UC-MSCs and PRCR improved the subchondral bone mass parameters; promoted the expression of ALP, RUNX2, and VEGF; suppressed osteoclast overactivity; and resisted cell apoptosis. The combination of PRCR and UC-MSCs shows promising therapeutic effects in treating glucocorticoid-induced ONFH. The current study provides important information on intra-articular therapy, paving the way for the clinical management of ONFH in the future.

9.
BMC Musculoskelet Disord ; 23(1): 151, 2022 Feb 15.
Article En | MEDLINE | ID: mdl-35168574

BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro. METHODS: In this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins. RESULTS: We observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro. CONCLUSION: Our vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.


Mesenchymal Stem Cells , Platelet-Rich Plasma , Animals , Bone Marrow Cells , Cell Differentiation , Cells, Cultured , Glucocorticoids/toxicity , Osteogenesis , Rats
10.
Front Med (Lausanne) ; 8: 732410, 2021.
Article En | MEDLINE | ID: mdl-34722573

Objective: To examine the clinical significance of the blood lactate (Lac)/serum albumin (Alb) ratio and the Lac/Alb × age score for assessing the severity and prognosis of patients with sepsis. Methods: A total of 8,029 patients with sepsis, aged >18 years were enrolled between June 2001 to October 2012 from the latest version of the Medical Information Mart for Intensive Care III (MIMIC-III v.1.4). The general data of the patients were obtained from hospital records and included gender, age, body mass index (BMI), laboratory indices, the sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS II). The patients were graded and scored according to their age and then divided into a survival or death group based on their prognosis. The Lac/Alb ratio after ICU admission was calculated and compared between the two groups. The risk factors for death in patients with sepsis were determined using multivariate logistic regression analysis, while mortality was examined using receiver operating characteristic (ROC) curve and survival curve plots. Finally, the values of the Lac/Alb ratio and Lac/Alb × age score for assessing prognosis of patients with sepsis were analyzed and compared. Results: After items with default values were excluded, a total of 4,555 patients with sepsis were enrolled (2,526 males and 2,029 females). 2,843 cases were classified as the death group and 1,712 cases in the survival group. (1) The mean age, BMI, SOFA and SAPS II scores were higher in the death group than those in the survival group. Significant differences in baseline data between the two groups were also observed. (2) The patients in the death group were divided further into four subgroups according to the quartile of the Lac/Alb ratio from low to high. Comparison of the four subgroups showed that the death rate rose with an increase in the Lac/Alb ratio, while analysis of the survival curve revealed that patients with a higher Lac/Alb ratio had a worse prognosis. (3) Multivariate logistic regression analysis showed that age ≥ 60 years, overweight (BMI ≥ 24 kg/m2), Lac/Alb ratio ≥ 0.16, SOFA score ≥ 2 points, and SAPS II ≥ 40 points were independent risk factors for death in patients with septic. (4) ROC curve analysis indicated that the SAPS II, Lac/Alb x age score, SOFA, and Lac/Alb ratio were the best predictors of death in patients with sepsis. The Lac/Alb × age score was characterized by its simple acquisition and ability to quickly analyze the prognosis of patients. Conclusion: (1)A high Lac/Alb ratio is an independent risk factor for death in patients with sepsis. (2) Although the prognosis of sepsis can be accurately and comprehensively assessed by multi-dimensional analysis of multiple indices, the Lac/Alb × age score is more accurate and convenient for providing a general assessment of prognosis, so is worthy of further clinical recognition.

12.
Ultrasound Med Biol ; 47(10): 2936-2940, 2021 10.
Article En | MEDLINE | ID: mdl-34266679

Intra-articular injection is frequently used as an effective diagnostic and treatment tool for hip joint diseases. However, the underlying treatment mechanism remains unclear because of a lack of experimental animal models. A challenge facing researchers is how to accurately and consistently perform injections involving animal hip joints. The purpose of this study, then, was to establish an ultrasound (US)-guided intra-articular (IA) injection technique using rat hip joints and to evaluate its accuracy and feasibility versus a fluoroscopy (FL)-guided technique. For this study, 20 US-guided and 20 FL-guided IA injections were administered to separate groups of Sprague-Dawley rats. For each procedure, 50 µL of iohexol was injected into the hip joint using a 25G needle. The US-guided injections were performed using a linear probe, and the FL-guided IA injections were performed using C-arm X-ray fluoroscopy. All injections were verified by computed tomography imaging. The number of successful injections and needle repositions per injection, as well as operating times, were recorded, and the rats were observed for complications for 10 d after the injections. Statistical analysis was used to compare US-guided and FL-guided techniques with significance set at p < 0.05. The success rate was markedly higher for the US-guided interventions (90%) than for the FL-guided interventions (75%) (p<0.05). The intervention time was shorter in the US-guided group (95.95 ± 8.376 s) than in the FL-guided group (110.70 ± 20.236 s) (p < 0.05), and the median number of needles repositioned per injection in the US-guided group (1.20 ± 0.41) was notably less than that in the FL-guided group (1.60 ± 0.68) (p < 0.05). A puncture site hematoma was noted in two rat hips (10%) the day after injection in the FL-guided group. Overall, the study indicated that ultrasound-guided intra-articular injection of the hip is a feasible, accurate and safe method for use in rats. This makes it a promising tool for diagnosing coxofemoral pain, producing hip osteoarthritis animal models and administering intra-articular medication.


Hip Joint , Ultrasonography, Interventional , Animals , Feasibility Studies , Hip Joint/diagnostic imaging , Injections, Intra-Articular , Rats , Rats, Sprague-Dawley
13.
Stem Cell Res Ther ; 12(1): 377, 2021 07 02.
Article En | MEDLINE | ID: mdl-34215342

OBJECTIVES: Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies. METHODS: The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases. RESULTS: Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV). CONCLUSION: This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.


Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Animals , Bone Regeneration , Bone and Bones , Osteogenesis
14.
FEBS J ; 288(14): 4364-4381, 2021 07.
Article En | MEDLINE | ID: mdl-33492759

Inhibitor of DNA-binding 1 (ID1) protein has been studied intensively for its functions in tumorigenesis and maintenance of stem cell-like properties, but its roles in virus infection are less understood. In the present study, we have clearly shown that the foot-and-mouth disease virus (FMDV) promotes ID1 degradation via Cdh1-mediated ubiquitination to facilitate its replication. Mechanistic investigations reveal Forkhead Box O1 (FOXO1) as an ID1 partner, which suppresses interferon regulatory factors 3 expression and interferon (IFN) production. Further investigation identified that ID1 suppresses FOXO1 transcription activity through HDAC4-mediated deacetylation, promoting IFN production and antiviral immune response. These studies establish a prominent role for ID1 in suppressing FDMV replication, which may be extended to other viruses.


Foot-and-Mouth Disease Virus/isolation & purification , Foot-and-Mouth Disease/prevention & control , Host-Pathogen Interactions , Inhibitor of Differentiation Protein 1/physiology , Virus Replication , Acetylation , Animals , Female , Foot-and-Mouth Disease/virology , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferons/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout
15.
Genes (Basel) ; 11(10)2020 09 27.
Article En | MEDLINE | ID: mdl-32992599

Emerging evidence indicates that the host microRNAs (miRNAs) are important intracellular regulators and play pivotal roles in intricate host-pathogen interaction networks. In our previous studies, ssc-microRNA-4334-5p (miR-4334-5p) was identified as a differentially expressed miRNA in microarray-based miRNAs profiling experiment, but whether miR-4334-5p regulates foot and mouth disease virus (FMDV) propagation is less understood. Here, we demonstrated that miR-4334-5p expression level was up-regulated shortly after FMDV infection, transfection of miR-4334-5p mimics promoted, while inhibitor transfection suppressed FMDV replication correspondingly. Further bioinformatic analysis and experimental study suggested ID1 was the direct target of miR-4334-5p, suppressing FMDV replication by regulating interferon (IFN) pathways. These findings shed light on microRNAs-ID1-interferon axis in regulating FMDV replication.


Foot-and-Mouth Disease Virus/pathogenicity , Foot-and-Mouth Disease/virology , Host-Pathogen Interactions , Inhibitor of Differentiation Protein 1/antagonists & inhibitors , Interferon Type I/antagonists & inhibitors , Kidney/virology , MicroRNAs/genetics , Animals , Cells, Cultured , Cricetinae , Foot-and-Mouth Disease/genetics , Foot-and-Mouth Disease/metabolism , Kidney/metabolism , MicroRNAs/metabolism , Signal Transduction , Swine
16.
Virus Res ; 286: 198064, 2020 09.
Article En | MEDLINE | ID: mdl-32574680

MicroRNAs play vital roles in regulating the battle between pathogens and host cells during viral challenging. MiR-4331 aggravates transmissible gastroenteritis virus (TGEV) -induced mitochondrial damage, also suppresses transcription of TGEV gene 7 via targeting cellular CDCA7. Otherwise, miR-4331-5p affects H1N1/2009 influenza A virus replication by targeting viral HA and NS. However, whether microRNA ssc-miR-4331-5p (miR-4331-5p) regulates foot and mouth virus (FMDV) replication remains unclear. To explore the role of miR-4331-5p in FMDV infection, we detected the expression level of miR-4331-5p in porcine kidney (PK-15) cells. The results showed that FMDV infection directly upregulates miR-4331-5p expression, while transfection of mimics or inhibitor of miR-4331-5p promotes or inhibits FMDV replication. Further investigation clearly showed that miR-4331-5p increases FMDV replication through inhibiting type I interferon pathways. These data demonstrate that miR-4331-5p plays an important role in regulating FMDV replication.


Foot-and-Mouth Disease Virus/physiology , Host-Pathogen Interactions , Interferon Type I/antagonists & inhibitors , MicroRNAs/genetics , Virus Replication , Animals , Cell Line , Foot-and-Mouth Disease Virus/genetics , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Interferon Type I/immunology , MicroRNAs/immunology , Swine , Up-Regulation
17.
Dis Aquat Organ ; 139: 25-33, 2020 Apr 30.
Article En | MEDLINE | ID: mdl-32351234

The major antigenic protein of infectious hematopoietic necrosis virus (IHNV) is the surface glycoprotein G, which contains neutralizing epitopes that induce the production of immune neutralizing antibodies. In this study, the IHNV G gene sequence was truncated according to bioinformatics principles and then recombinantly expressed via an E. coli expression system. We then assessed the specific antibody immunoglobin M (IgM) levels of rainbow trout immunized with recombinant truncated G protein (emulsified with Freund's incomplete adjuvant), and showed that antibody IgM levels of immunized fish were significantly higher than in the control group (p < 0.01). The mRNA expression levels of interferon 1 (IFN1) and interleukin-8 (IL-8) were also up-regulated significantly (p < 0.01) in head kidneys and spleens of rainbow trout immunized with recombinant truncated G protein. Also, after challenge with wild-type IHNV HLJ-09 virus on Day 28, rainbow trout immunized with recombinant truncated G protein showed cumulative survival rates of 60%. These results indicate that the truncated G protein of IHNV expressed by the E. coli prokaryotic expression system can be used as a candidate immunogen for an IHNV subunit vaccine, which lays a theoretical foundation for the study of further potential IHNV subunit vaccines.


Fish Diseases , Infectious hematopoietic necrosis virus , Oncorhynchus mykiss , Animals , Disease Resistance , Escherichia coli
18.
Med Sci Monit ; 25: 6598-6604, 2019 Sep 03.
Article En | MEDLINE | ID: mdl-31477682

BACKGROUND The aim of this study was to evaluate the influence of distal radius fractures (DRFs) malalignment on the treatment outcomes in patients over age 65 years. MATERIAL AND METHODS We retrospectively reviewed the records on fresh DRFs treated with closed reduction from December 2014 to January 2018. After treatment, patients were evaluated for the determination of grip strength, the Visual Analog Scale (VAS) during wrist movement, the Patient-Rated Wrist Evaluation (PRWE), the Disabilities of the Arm, Shoulder and Hand (DASH) score, the appearance satisfaction, and active wrist range of motion (ROM). RESULTS A total of 96 patients with complete data were included in our study. During follow-up, there were 75 patients (78.1%) with acceptable reduction and 21 patients (21.9%) with unacceptable reduction. Compared with those having acceptable alignment in the distal radius, patients with unacceptable alignment had weak grip strength, were unsatisfied appearance, and had severe flexion as well as ulnar deviation limitation at 6-month follow-up. A significant correlation was found between ulnar positive variance and grip strength (r=-0.35, P=0.03), as well as dorsal angulation and flexion movement (r=-0.31, P=0.02). CONCLUSIONS Conservative treatment should be used differently, even in elderly patients. For low-demand patients, it is not necessary to restore all anatomic radiographic parameters, as malalignment does not increase disability or pain score. However, for patients who are still healthy and active, satisfactory reduction is the first choice, as malalignment can lead to decreased grip strength, dissatisfaction with appearance, and certain wrist limitations.


Radius Fractures/diagnostic imaging , Aged , Disability Evaluation , Female , Follow-Up Studies , Hand Strength , Humans , Male , Pain/physiopathology , Radius Fractures/physiopathology , Range of Motion, Articular
19.
Cancer Cell Int ; 19: 158, 2019.
Article En | MEDLINE | ID: mdl-31198407

BACKGROUND: As a pivotal regulator, cyclin D3 gives play to a crucial value in conversion from the G1 stage to the S stage of cell cycle, which is implicated in tumor progression, especially proliferation and migration. Recent literatures have reported that cyclin D3 could predict survival time of malignancy patients. But, its prognostic role of cyclin D3 in neoplasms remains controversial. METHODS: Databases involving EMBASE, PubMed and Web of Science were carefully searched, and literatures investigating the prognostic effect of aberrantly expressing cyclin D3 among human cancers were collected for further analysis. We used both hazards ratios and its corresponding 95% confidence intervals to evaluate the connection among the survival rate of malignancy patients and the expression of cyclin D3. RESULTS: There were 13 eligible researches involving 16 cohorts and 2395 participants which were included in this study. The outcomes suggested that highly expressing cyclin D3 was significantly correlated with worse clinical prognosis of overall survival (HR 1.88; 95% CI 1.31-2.69) and disease specific survival (HR 2.68; 95% CI 1.35-5.31). But there existed no significant connection between the elevated expression of cyclin D3 with disease free survival (HR 2.65; 95% CI 0.83-8.46), recurrence-free survival (HR 2.86; 95% CI 0.82-9.96) and progression-free survival (HR 5.24; 95% CI 0.46-60.25) of diffident kinds of malignancy patients. Moreover, we discovered that elevated cyclin D3 expression was significantly connected with decreased overall survival in lymphoma (HR 3.72; 95% CI 2.18-6.36) while no significant relevance between highly expressing cyclin D3 and the overall survival in breast cancer was obtained (HR 2.12; 95% CI 0.76-5.91). CONCLUSIONS: This meta-analysis demonstrated that highly expressing cyclin D3 might be an unfavorable prognostic biomarker for various malignancy patients, which can make great contributions to the clinical diagnosis and treatment.

20.
Sensors (Basel) ; 19(9)2019 May 06.
Article En | MEDLINE | ID: mdl-31064125

Bearing fault diagnosis of a rotating machine plays an important role in reliable operation. A novel intelligent fault diagnosis method for roller bearings has been developed based on a proposed hybrid classifier ensemble approach and the improved Dempster-Shafer theory. The improved Dempster-Shafer theory well considered the combination of unreliable evidence sources, the uncertainty information of basic probability assignment, and the relative credibility of the evidence on the weights in the process of decision making under the framework of fuzzy preference relations, which can effectively deal with conflicts of the evidences and then well improve the diagnostic accuracy for the hybrid classifier ensemble. The effectiveness of the improved Dempster-Shafer theory has been verified via a numerical example. In addition, deep neural networks, a support vector machine, and extreme learning machine techniques have been utilized in the single-stage classification based on singular spectrum entropy, power spectrum entropy, time-frequency entropy, and wavelet packet energy spectrum entropy in this work. Performances of the proposed hybrid ensemble classifier has been demonstrated on a bearing test-rig, compared with the original Dempster-Shafer theory. It can be found that the overall error rate can be greatly reduced with the hybrid ensemble classifier and the improved Dempster-Shafer theory.

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