ABC2A: A Straightforward and Fast Method for the Accurate Backmapping of RNA Coarse-Grained Models to All-Atom Structures.

RNAs play crucial roles in various essential biological functions, including catalysis and gene regulation. Despite the widespread use of coarse-grained (CG) models/simulations to study RNA 3D structures and dynamics, their direct application is challenging due to the lack of atomic detail. Therefore, the reconstruction of full atomic structures is desirable. In this study, we introduced a straightforward method called ABC2A for reconstructing all-atom structures from RNA CG models. ABC2A utilizes diverse nucleotide fragments from known structures to assemble full atomic structures based on the CG atoms. The diversification of assembly fragments beyond standard A-form ones, commonly used in other programs, combined with a highly simplified structure refinement process, ensures that ABC2A achieves both high accuracy and rapid speed. Tests on a recent large dataset of 361 RNA experimental structures (30-692 nt) indicate that ABC2A can reconstruct full atomic structures from three-bead CG models with a mean RMSD of ~0.34 Å from experimental structures and an average runtime of ~0.5 s (maximum runtime < 2.5 s). Compared to the state-of-the-art Arena, ABC2A achieves a ~25% improvement in accuracy and is five times faster in speed.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.

Objective: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. Methods: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. Results: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. Conclusion: These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

[Research and application of model fruit fly in prevention and treatment of neuropsychiatric disorders by traditional Chinese medicine and natural compounds: a review].

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

Pathogenicity and Pathotype Analysis of Henan Isolates of Marek's Disease Virus Reveal Long-Term Circulation of Highly Virulent MDV Variant in China.

In recent years, outbreaks of Marek's disease (MD) have been frequently reported in vaccinated chicken flocks in China. Herein, we have demonstrated that four Marek's disease virus (MDV) isolates, HN502, HN302, HN304, and HN101, are all pathogenic and oncogenic to hosts. Outstandingly, the HN302 strain induced 100% MD incidence, 54.84% mortality, and 87.10% tumor incidence, together with extensive atrophy of immune organs. Pathotyping of HN302 was performed in comparison to a standard very virulent (vv) MDV strain Md5. We found that both CVI988 and HVT vaccines significantly reduced morbidity and mortality induced by HN302 or Md5 strains, but the protection indices (PIs) provided by these two vaccines against HN302 were significantly lower (27.03%) or lower (33.33%) than that against Md5, which showed PIs of 59.89% and 54.29%, respectively. These data suggested that HN302 possesses a significant higher virulence than Md5 and at least could be designated as a vvMDV strain. Together with our previous phylogenetic analysis on MDV-1 meq genes, we have presently suggested HN302 to be a typical highly virulent MDV variant belonging to an independent Chinese branch. To our knowledge, this is the first report to provide convincible evidence to identify a pathogenic MDV variant strain with a higher virulence than Md5 in China, which may have emerged and circulating in poultry farms in China for a long time and involved in the recent MD outbreaks.

Efficacy and safety of Chinese herbal medicine Qirui Weishu capsule in treating chronic non-atrophic gastritis: A multicentre, double-blind, randomized controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001)，especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.

Luteolin Enhances Choroid Plexus 5-MTHF Brain Transport to Promote Hippocampal Neurogenesis in LOD Rats.

Folates, provided by food, are commonly used antidepressant synergists in late-onset depression (LOD). However, increased intake of folic acid in the elderly population might lead to the accumulation of unmetabolized folic acid in the systemic circulation, leading to enhanced deterioration of the central nervous system function. In addition, folates cannot access the brain directly because of the blood-brain barrier. Choroid plexus (CP) 5-methyltetrahydrofolate (5-MTHF) brain transport plays a critical role in regulating the cerebrospinal fluid (CSF) 5-MTHF content. Luteolin is a natural flavonoid that has antidepressant effects and is involved in the anti-folate resistance pathway. It remains unclear whether the antidepressant effects of luteolin are associated with the CP 5-MTHF brain transport. In this study, 20-21-month-old Wistar rats were exposed to the chronic unpredictable mild stress (CUMS) protocol for 6 consecutive weeks to explore the long-term effects of luteolin on behavior, 5-MTHF levels, hippocampal neurogenesis, and folate brain transport of the CP. In vitro primary hippocampal neural stem cells (NSCs) cultured in media containing 10% CSF from each group of rats and choroid plexus epithelial cells (CPECs) cultured in media containing 20 µM luteolin were treated with 100 µM corticosterone and 40 mg/ml D-galactose. We found that aged rats exposed to CUMS showed a significantly reduced sucrose preference, decreased locomotion activity in the open field test and accuracy of the Morris water maze test, increased immobility time in the forced swimming test, accelerated dysfunctional neurogenesis and neuronal loss in the dentate gyrus of LOD rats, as well as decreased CSF and hippocampus 5-MTHF levels, and zona occludens protein 1 (ZO-1), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC) protein levels. In vitro assays showed media containing 10% aged CSF or LOD+ Luteolin-CSF significantly increased the viability of CORT + D-gal-injured NSCs and alleviated dysfunctional neurogenesis and neuronal loss compared with the CORT + D-gal medium. However, media containing 10% LOD-CSF had no such effect. In the meantime, induction of CORT + D-gal significantly decreased the ZO-1, PCFT, RFC, and folate receptor alpha (FR-α) protein levels and transepithelial electrical resistance in rat CPECs. As expected, luteolin treatment was effective in improving these abnormal changes. These findings suggested that luteolin could ameliorate CUMS-induced LOD-like behaviors by enhancing the folate brain transport.

Alterations in the expression level of visfatin in the lungs of piglets infected with PRRSV and its effect on PRRSV replication.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by PRRS virus (PRRSV), characterized by sow reproductive failure and respiratory symptoms in pigs of all ages. PRRSV mainly causes severe lung damage by invading alveolar macrophages. Visfatin is closely related to acute lung injury, immune response and inflammation along with virus invasion to the host. Therefore, the current study was performed to clarify the relationship between visfatin and PRRSV infection. We used ternary piglets to construct a piglet model to explore the expression of visfatin and tight junction protein in lung injury induced by PRRSV infection, and then further studied the inhibition effect of visfatin on PRRSV replication by PRRSV infection of Marc-145 cells. Our results indicated that both PRRSV attenuated and virulent infections could damage the lung tissues, which could not only lead to severe inflammatory reaction (such as increased expression of TNF-α, TGF-ß, IL-8 and IL-10) in lung tissues of piglets, but also brought about the sharp decrease of ZO-1 and Tricellulin expressions resulting in impaired alveolar epithelial barrier. Meanwhile, we found significantly up-regulated expression of visfatin in lungs and serum of pigs after PRRSV infection that were related to both the degree of lung injury and the virulence of PRRSV strain. Moreover, visfatin might inhibit the PRRSV infection to Marc-145 cells in time dependent fashion. Hence, the current investigation provides the novel information about the effect of visfatin and PRRSV co-culture on Marc-145 cells and the effect of visfatin on PRRSV proliferation at different time points.

3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study.

Objective: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods: From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results: Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion: The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Exploration of the mechanism by which icariin modulates hippocampal neurogenesis in a rat model of depression.

Icariin (ICA) has a significant capacity to protect against depression and hippocampal injury, but it cannot effectively cross the blood-brain barrier and accumulate in the brain. Therefore, the mechanism by which ICA protects against hippocampal injury in depression remains unclear. In this study, we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression. A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks, after which 120 mg/kg ICA was administered subcutaneously every day. The results showed that ICA alleviated depressive symptoms, learning and memory dysfunction, dysfunctional neurogenesis, and neuronal loss in the dentate gyrus of rats with depression. Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 µM corticosterone. The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation. Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid. These proteins were mainly involved in the ribosome, PI3K-Akt signaling, and interleukin-17 signaling pathways. Parallel reaction monitoring mass spectrometry showed that Rps4x, Rps12, Rps14, Rps19, Hsp90b1, and Hsp90aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA. In contrast, HtrA1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA. These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid. The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.

[Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression].

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

Cerebrospinal fluid proteomics reveal potential protein targets of JiaWeiSiNiSan in preventing chronic psychological stress damage.

CONTEXT: Chinese herbal formula JiaWeiSiNiSan (JWSNS) has been widely used to prevent stress-induced neuropsychiatric ailments in clinics and proven to have therapeutic anti-stress effects on rats. However, the mechanism remains unclear. OBJECTIVE: Based on the proteomics of cerebrospinal fluid (CSF), this study explores the possible mechanism and target proteins of JiaWeiSiNiSan raising stress resilience and preventing stress damage. MATERIALS AND METHODS: A 6-week Chronic Unpredictable Mild Stress (CUMS) model was applied on adult Wistar male rats to observe the effects of JWSNS on improving mental stress resilience. Tandem Mass Tag (TMT) proteomics and bioinformatics analysis were used to screen and analyze differentially expressed proteins (DEPs) in CSF. Parallel Reaction Monitoring (PRM) was used to validate target DEPs. RESULTS: Significantly decreased sucrose preference, locomotion activity level and accuracy of T-maze, as well as increased immobility time, were observed in CUMS rats compared to CON rats while JWSNS improved above depression-like behaviours. The quantitative proteomics and bioinformatics analysis showed that JWSNS decreased the expression of Rps4x, HSP90AA1, Rps12, Uba1, Rsp14, Tuba1b in CUMS rats CSF (p < 0.05, FDR < 0.5). Immunofluorescence results showed that the number of BrdU/DCX positive cells (p < 0.01) and the relative number of neurons (p < 0.01) in the hippocampus dentate gyrus (DG) of the JSWNS group significantly increased, compared with the CUMS group. CONCLUSIONS: JWSNS could increase mental stress resilience and prevent stress damage by regulating proteins in CSF. This study provides a scientific basis for further study on Chinese formulas preventing mental illness.

Visfatin Regulates Inflammatory Mediators in Mouse Intestinal Mucosa Through Toll-Like Receptors Signaling Under Lipopolysaccharide Stress.

Visfatin is a multifunctional protein involved in inflammatory immune stress. The aim of current study was to explore the role of visfatin in lipopolysaccharide (LPS)-induced intestinal mucosal inflammation and to confirm its cellular effect in inflammatory immune response through silencing of Toll-like receptors (TLRs). We divided Kunming mice into three groups: Saline group, LPS group, and LPS + visfatin group and performed hematoxylin and eosin staining, immunohistochemistry, quantitative polymerase chain reaction, Western blot, enzyme linked immunosorbent assay and RNA-seq analysis. Pretreatment of visfatin improves LPS-stimulated reduction of tight junction protein 1 (ZO-1) and secretory immunoglobulin A, inhibits overexpression of Claudin-1 and vascular endothelial growth factor, and reduces intestinal mucosal damage and inflammation. RNA-seq analysis of cellular transcriptomes indicated that visfatin is involved in down-regulation of mRNA level of TLR4 as well as attenuation of protein levels of TLR8 and nucleotide-binding oligomerization domain-containing protein 2, revealing that visfatin could reduce intestinal mucosal inflammation through TLR signaling pathway in mice ileum. In RAW264.7 cells, the genes silencing of Toll/IL-1R family, such as TLR4, TLR2, and IL-1R1, was accompanied by decreased expressions of inflammatory factors (TNF-α, IL-1ß, IL-6 and MCP-1) along with lower cellular visfatin levels. Hence, visfatin maintains the intestinal mucosal barrier structure and attenuates the intestinal mucosal inflammation through the TLR signaling pathway. Likewise, the Toll/IL-1R family regulates the release of visfatin, which can participate in the inflammatory reaction through the regulation of inflammatory factors.

Optimization and bioactivity verification of porcine recombinant visfatin with high expression and low endotoxin content using pig liver as template.

In order to obtain the porcine recombinant visfatin protein with high expression and low endotoxin content, the current study aims to express and verify the biological activity of the purified porcine recombinant visfatin protein. Firstly, four different expression strains were successfully constructed. Then they were simultaneously induced at 37 °C for 4 h and 16 °C for 16 h. The results showed that Visfatin-pET28a-Transetta was the best strain with high protein expression and purity at 16 °C induction for 16 h. After that, endotoxin was reduced from the recombinant visfatin until the residual endotoxin was less than one endotoxin units per milliliter (EU/mL). Finally, the purified porcine recombinant visfatin protein was incubated with RAW264.7 cells. The results of cell counting kit-8 (CCK-8) showed the survival rate of the cells first increased and then decreased with the increase in visfatin concentration. When the concentration of visfatin was 700 ng/mL, the survival rate of the cells was the highest. Thereafter, control (PBS), Visfatin and Visfatin + PolymyxinB (Ploy.B) groups were incubated with the RAW264.7 cells for 6 h. Real-time quantitative polymerase chain reaction (RT-qPCR) and Enzyme Linked Immuno-Sorbent Assay (ELISA) results showed that, as compared to the control group, the expressions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in Visfatin group were significantly increased (P < 0.05). However, there was no significant difference between the Visfatin and Visfatin + Poly.B groups, indicating that porcine recombinant visfatin protein promoted the inflammatory activity of RAW264.7 cells while the residual endotoxin did not play a role, suggesting biological activity of porcine recombinant visfatin protein.

Virus-encoded miR-155 ortholog in Marek's disease virus promotes cell proliferation via suppressing apoptosis by targeting tumor suppressor WWOX.

Marek's disease virus serotype 1 (MDV-1) is an important oncogenic α-herpesvirus that induces immunosuppressive and rapid-onset T-cell lymphomatous disease in poultry commonly referred to as Marek's disease (MD). As an excellent biomodel for the study of virally-induced cancers in natural hosts, MDV-1 encoded microRNAs (miRNAs) have been previously demonstrated with the potential roles to act as critical regulators in virus replication, latency, pathogenesis and especially in oncogenesis. Similar to the oncogenic γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), miR-M4-5p, the cellular microRNA-155 (miR-155) ortholog encoded by MDV-1, is also involved in MD oncogenesis. In lymphoblastoid cell lines derived from MDV-induced T-cell lymphomas, miR-M4-5p has been shown to be highly expressed and participate in inducing MD lymphomagenesis by regulating multiple signal pathways. Herein we report the new identification of the host WW domain-containing oxidoreductase (WWOX) as a biological target for miR-M4-5p. Further experiments revealed that as a critical oncomiRNA, miR-M4-5p promotes the proliferations of both chicken embryo fibroblast (CEF) and MSB-1 cells via suppressing cell apoptosis by targeting WWOX, a well-known tumor suppressor. Our data presents a novel insight in elucidating the regulatory mechanisms mediated by the viral analog of miR-155 that potentially contribute to MD tumorigenesis.

Marek's Disease Virus (Gallid alphaherpesvirus 2)-Encoded miR-M2-5p Simultaneously Promotes Cell Proliferation and Suppresses Apoptosis Through RBM24 and MYOD1-Mediated Signaling Pathways.

MicroRNAs (miRNAs) have been demonstrated for their involvement in virus biology and pathogenesis, including functioning as key determinants of virally-induced cancers. As an important oncogenic α-herpesvirus affecting poultry health, Marek's disease virus serotype 1 [Gallid alphaherpesvirus 2 (GaHV-2)] induces rapid-onset T-cell lymphomatous disease commonly referred to as Marek's disease (MD), an excellent biological model for the study of virally-induced cancer in the natural hosts. Previously, we have demonstrated that GaHV-2-encoded miRNAs (especially those within the Meq-cluster) have the potential to act as critical regulators of multiple processes such as virus replication, latency, pathogenesis, and/or oncogenesis. In addition to miR-M4-5p (miR-155 homolog) and miR-M3-5p, we have recently found that miR-M2-5p possibly participate in inducing MD lymphomagenesis. Here, we report the identification of two tumor suppressors, the RNA-binding protein 24 (RBM24) and myogenic differentiation 1 (MYOD1), being two biological targets for miR-M2-5p. Our experiments revealed that as a critical miRNA, miR-M2-5p promotes cell proliferation via regulating the RBM24-mediated p63 overexpression and MYOD1-mediated IGF2 signaling and suppresses apoptosis by targeting the MYOD1-mediated Caspase-3 signaling pathway. Our data present a new strategy of a single viral miRNA exerting dual role to potentially participate in the virally-induced T-cell lymphomagenesis by simultaneously promoting the cell proliferation and suppressing apoptosis.

Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules.

BACKGROUND: Recent research suggests that although prokinetic agents, acid suppressors, and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia (FD), a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions. Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases. The present study was designed to verify the efficacy of Biling Weitong Granules (BLWTG), a traditional Chinese medicinal herbal compound formula, in alleviating epigastric pain syndrome (EPS) in FD patients, in an attempt to provide an effective prescription for the clinical treatment of this disease. AIM: To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD. METHODS: In this multicenter, stratified, randomized, double-blind, placebo-controlled, parallel group clinical trial, eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk. Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared. RESULTS: The baseline demographic data and clinical characteristics, such as epigastric pain symptoms, pain intensity, and frequency of attacks, were matched between the two groups before randomization. After 6 wk of treatment and after the center effect was eliminated, the epigastric pain was significantly improved in 28.33% and 85.59% of the patients in the placebo and BLWTG groups, respectively (P < 0.05). At 6 wk, the resolution rate of epigastric pain was 15% and 69.49% in the placebo and BLWTG groups, respectively (P < 0.05). The differences of total FD clinical score between these two groups were significant (P < 0.05) at 2, 4, and 6 wk (P < 0.05). The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups, and no serious adverse event was noted during the observation. CONCLUSION: Compared with placebo, BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.

[Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory factors in rheumatoid arthritis].

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1ß(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1ß(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1ß(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1ß(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1ß(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

[Meta-analysis of RCT studies on clinical efficacy of single administration of Tripterygium Glycosides Tablets or combined administration with methotrexate against rheumatoid arthritis].

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.

Visfatin Exerts Immunotherapeutic Effects in Lipopolysaccharide-Induced Acute Lung Injury in Murine Model.

Visfatin acts as a significant regulator of inflammatory cytokines. However, the immunological response and therapeutic effects of visfatin under bacterial stress in murine lung tissue are still not clear. To investigate the role of visfatin on lipopolysaccharide (LPS)-induced acute lung injury (ALI), thirty Kunming mice were divided into Saline, LPS, and LPS + visfatin groups. After routine blood examination, the effects of visfatin on inflammatory cytokines, lung tissue structure, and expression of inflammatory mediators were explored through hematoxylin-eosin (H&E), Masson and immunohistochemical staining, quantitative polymerase chain reaction (Q-PCR), and Western blotting. Compared with the Saline group, neutrophil percentage, peripheral blood neutrophil count, and the ratio of lymphocyte count (NLR) were upregulated in LPS group. Moreover, Masson staining showed alterations in lung tissue structure; the mRNA level of different cytokines (IL-6, IL-1ß, TNF-α, IL-10, TLR4, IFN-γ) was upregulated; and the protein expression of interleukin (IL)-6, myeloperoxidase (MPO), and transforming growth factor-ß1 (TGF-ß) was significantly (p < 0.05) different in LPS group. Compared with LPS group, neutrophil percentage significantly decreased (p < 0.01), the numbers of lymphocytes significantly (p < 0.05) increased, NLR decreased, Masson staining of the lung was extremely different (p < 0.01), the structure of the lung was slightly damaged, and the myeloperoxidase values of lung showed no differences in LPS + visfatin. Hence, visfatin inhibits the lung inflammation induced by ALI. During the ALI, visfatin acts by decreasing NLR, downregulated the expression of MPO, enhanced antioxidant capacity, and regulated the inflammatory factors IL-1ß, IL-6, IL-10, and TNF-α to reduce the lung injury.

[Toxicity-reducing effect of compatibility of Tripterygium and licorice in animals: systematic review].

The aim of this paper was to systematically evaluate the toxicity-reducing effect of Tripterygium-licorice in animal experiments,and also to provide evidence for basic research on the toxicity reduction of Tripterygium wilfordii. The PubMed,EMbase,Web of Science,CBM,CNKI and Wan Fang Databases from their establishment to August 31 th,2018 were searched. Two independent reviewers screened the papers,extracted the data,assessed the risk of bias using SYRCLE assessment tool and conducted Meta-analysis with Rev Man 5. 3 software. A total of 10 papers involving 31 studies were finally included,15 studies of which were used for Meta-analysis. Four studies were included for chronic hepatotoxicity animal model. In experimental group( 34 animals),Tripterygium was administered at dose of 0. 09-0. 1 mg·kg-1·d-1,and glycyrrhizic acid was administered at dose of 90-100 mg·kg-1,both for 2 weeks; in control group( 34 animals),glycyrrhizic acid was replaced with equal volume of normal saline. Eleven studies were included for acute hepatotoxicity animal model. In experimental group( 66 animals),glycyrrhizic acid was administered at dose of 75-480 mg·kg-1 for 7 days,then glycyrrhizic acid was stopped,and Tripterygium began to be administered at dose of 0. 6-1. 0 mg·kg-1 per 24 h or 48 h for a total of 1-2 times; in control group( 66 animals),glycyrrhizic acid was replaced with equal volume of normal saline or corresponding solvent. The results of Meta-analysis showed that in both chronic hepatotoxicity animal model and acute hepatotoxicity animal model,the transaminase levels in the experimental group were lower than those in the control group( P < 0. 05). Subgroup analysis of acute hepatotoxicity animal model showed that the transaminase levels in the experimental group were lower than those in the control group for every subgroup except " glycyrrhizic acid 75 mg·kg-1" subgroup. However,in terms of the mean difference( MD) and confidence interval( CI),there was no significant difference in transaminase decline between each subgroup. Low dose of glycyrrhizic acid( 90-100 mg·kg-1) has a toxicity-reduction effect on chronic hepatotoxicity induced by tripterygium( 0. 09-0. 10 mg·kg-1). Middle and high doses of glycyrrhizic acid( 120-480 mg·kg-1) have a toxicity-reduction effect on acute hepatotoxicity induced by tripterygium( 0. 6-1. 0 mg·kg-1),but with no significant dose-effect relationship.