AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Objective To explore the expression and diagnostic value of circulating microRNA(miR)-126-3p in non-small cell lung cancer(NSCLC).Methods Multi-centred miR chips and sequencing data were col-lected to investigate the differential expression of circulating miR-126-3p in NSCLC.In order to evaluate the comprehensive expression level of circulating miR-126-3p in the cycle,the standardized mean difference(SMD)and summary receiver operating characteristic(sROC)curve were calculated,and the area under curve(AUC)of sROC curve was analyzed.Sensitivity,specificity,positive negative likelihood ratio were ex-plored,and the expression of circulating miR-126-3p was further comprehensively analyzed in combination with tissue.By using miRDB,starBase v2.0,and TargetScan 7.1,combined with up-regulated differentially expressed genes in NSCLC,potential target genes of circulating miR-126-3p were screened using complemen-tary sequence method.Results Based on six circulating miR datasets,the expression level of circulating miR-126-3p was higher than that of the control group,and the difference was statistically significant(P＜0.05).The receiver operating characteristic curves showed that circulating miR-126-3p had strong diagnostic efficacy(AUC＞0.5),and the comprehensive expression of circulating miR-126-3p was lower in 199 cases of NSCLC group than in the control group(SMD=-1.46).The sROC curve showed that circulating miR-126-3p distin-guished the NSCLC group from the control group with high accuracy(AUC=0.91),Egger's test showed no publication bias(P＞0.05),with sensitivity and specificity 0.80,and positive likelihood ratio and negative likelihood ratio were 5.37 and 0.18,respectively.In addition,a comprehensive analysis of the circulation and tissue of 1 320 NSCLC samples from 26 datasets showed that circulating miR-126-3p expression was lower in NSCLC group than in the control group(SMD=-2.07).The sROC curve showed that low-expression circu-lating miR-126-3p had high accuracy in distinguishing between the NSCLC group and the control group(AUC=0.97).In addition,potential target genes ADAM9 and SLC7A5 were screened for circulating miR-126-3p,and their expression in NSCLC group was higher than that in the control group.Conclusion Low ex-pression of circulating miR-126-3p in the circulation may be an important biomarker for high-precision screen-ing of NSCLC.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.

Mammalian mitochondrial genome encodes a small set of tRNAs, rRNAs, and mRNAs. The RNA synthesis process has been well characterized. How the RNAs are degraded, however, is poorly understood. It was long assumed that the degradation happens in the matrix where transcription and translation machineries reside. Here we show that contrary to the assumption, mammalian mitochondrial RNA degradation occurs in the mitochondrial intermembrane space (IMS) and the IMS-localized RNASET2 is the enzyme that degrades the RNAs. This provides a new paradigm for understanding mitochondrial RNA metabolism and transport.
Cell Line ; Humans ; Mitochondrial Membranes ; metabolism ; Protein Transport ; RNA ; biosynthesis ; chemistry ; metabolism ; RNA Stability ; RNA, Mitochondrial ; Ribonucleases ; metabolism ; Tumor Suppressor Proteins ; metabolism

The cDNA fragment of JEV prME gene was cloned into the baculovirus shuttle vector (bacmid) to construct a recombinant baculovirus vector, defined as AcBac-prME. Then the recombinant baculovirus Ac-prME was obtained by transfecting Sf9 cells with AcBac-prME. Western blot analysis and immunofluorescence results indicated that both prM and E proteins were efficiently expressed in Sf9 cells. Electron microscopy suggested that prME was assembled into JEV-VLPs. To further evaluate the potential of JEV-VLPs as vaccine, the mice were immunized with JEV-VLPs and then challenged with lethal JEV. The results of mice survival and pathological changes demonstrated that the JEV-VLPs performed complete protection against JEV-P3 strain and relieved pathological changes in the mice brain significant. This study suggest that JEV-VLPs would be a potential vaccine for Japanese encephalitis virus.
Animals ; Antibodies, Viral ; immunology ; Encephalitis Virus, Japanese ; genetics ; immunology ; Encephalitis, Japanese ; immunology ; prevention & control ; virology ; Humans ; Japanese Encephalitis Vaccines ; administration & dosage ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Sf9 Cells ; Vaccination ; Vaccines, Virus-Like Particle ; administration & dosage ; genetics ; immunology ; Viral Envelope Proteins ; administration & dosage ; genetics ; immunology

Objective To study the treatment effect of cinnamaldehyde on Aspergillus fumigatus biofilm(BF) in vitro .Meth‐ods The models of A .fumigatus BF were established in vitro ;the minimum inhibitory concentration(MIC) on A .fumigatus was measured .The crystal violet assay and scanning electron microscopy were employed to determined the treatment effect of A .fumiga‐tus biofilm under varying concentrations of cinnamaldehyde .Results BF models were established successfully in vitro .MIC value of A .fumigatus of cinnamaldehyde was 256 μg/mL ;The biofilm biomass in serially increasing concentrations of cinnamaldehyde(1 MIC ,1/2 MIC ,1/4 MIC)were 0 .81 ± 0 .11 ,1 .13 ± 0 .18 and 1 .59 ± 0 .11 respectively .Compared to untreated control group(2 .18 ± 0 .15) ,difference achieved statistical significance(P<0 .05) .SEM studies revealed the deformity of three‐dimensional structures of biofilms treated with sub‐MICs of cinnamaldehyde .Conclusion Cinnamaldehyde has significant antifungal activity against Aspergil‐lus fumigatus ,sub‐MICs could disrupt the mature biofilm in vitro .

Objective To evaluate the in vitro antifungal activity of Cinnamaldehyde in combination with Voriconazole (VRC) against clinically isolated Aspergillus fumigatus strains. Methods According to the Clinical and Laboratory Stan?dards Institute (CLSI) M38-A2 document,the minimal inhibitory concentrations (MIC) of Cinnamaldehyde and VRC alone or in combination against 42 clinical Aspergillus fumigatus isolates were determined by both microdillution method and check?board method respectively. The MIC50, MIC90, MICG and MICs distribution were compared between single drug and both in combination. The concentration-accumulative curve was drawn and fractional inhibitory concentration index (FICI) was cal?culated to evaluate the interaction between two test agents. Results The values of MIC50, MIC90 and MICG were significant?ly decreased (P<0.001) when combination of the two drugs than those of their single use, with their MIC distribution concen?tration-accumulative curves shifted to the left. The value of FICI of Cinnamaldehye-VRC combination ranged from 0.187 5 to 1.5. Sixteen strains (38.10%) of them showed the synergistic effect, 19 strains (45.23%) showed additive effect, and 7 strains (16.67%) showed an unrelated effect, and no antagonist effect on tested Aspergillus fumigatus strains in vitro. Conclu?sion Cinnamaldehye in combination with VRC mainly shows a combined synergic and additive inhibitory effect on Asper?gillus fumigatus isolates, and this combination appears to be more active against the test strains, which are less susceptible to voriconazole.

objective To introduce the design concept and structure of a new type of lumbar intervertebral fusion cage ,and to e-valuate its biomechanical properties .Method A partially bioasorbable interbody fusion cage(PBIFC) made of nano hydroxyapatite and poly amino acid /calcium sulfate copolymer materials was developed .Range of motion(ROM ) ,compressive load ,and pull-out test on flexion ,extension ,lateral bending ,and torsion moment on fresh calf L3/L4 specimens of functional spinal union were carried out of iliac bone group ,PBIFC group ,and nano hydroxyapatite/polyamide 66(nHA/PA66) group .Result Of each movement ,the ROM value of iliac bone group are higher than the other two groups ,the difference was statistically significant (P<0 .05) ,and the ROM value of nHA/PA66 group are higher than PBIFC group ,but no statistical difference(P>0 .05) .The pull-out strength of PB-IFC group are higher than iliac bone group ,and the difference was statistically significant (P<0 .05);The pull-out strength of PB-IFC group is lower than the traditional group ,but no statistical difference(P>0 .05) .The compressive load of iliac bone group was lower than that of two cage group ,the difference was statistically significant (P<0 .05) .The compressive load of PBIFC group is slightly lower than the traditional group ,but no statistical difference(P>0 .05) .Conclusion With good implant stability ,pull-out resistance ,and compression resistance performance ,PBIFC can meet the biomechanics requirements of clinical implant .

Objective To investigate the in vitro destructive effect of chlorogenic acid (CRA)/isochlorogenic acid (IRC)on Aspergillus fumigatus biofilm in a model of biofilm formation.Methods The in vitro biofilm model was established using clinical isolates of A.fumigatus.The minimum inhibitory concentrations (MIC)of antimicrobial agents against A.fumigatus were determined by microdilution method.Scanning electron microscope (SEM)and laser confocal scanning microscope (CLSM)were used to characterize the biofilm.Crystal violet staining method was used for biofilm quantitation.Results After reaction with CRA/IRC for 24 h or 48 h,observation of biofilm showed that A.fumigatus extracellular matrix was thinner than the control group.Biofilm quantitation showed that the optical densities were 1.05±0.19,1.14±0.26,0.99±0.14 for CRA group (1 024 mg/L,512 mg/L,256 mg/L);1.39±0.06,1.41±0.06,1.60±0.04 for IRC group (1 000 mg/L,500 mg/L,250 mg/L)at 24 h,and 1.91±0.17 for control group (P<0.05).The quantitation of biofilm showed that the optical densities were 2.25±0.05,2.27±0.05,2.31±0.03 for CRA group,2.26 ± 0.02,2.27±0.02,2.29±0.04 for IRC group at 48 h,and 2.36±0.01 for control group (P<0.05).Conclusions CRA/IRC has some inhibitory effect on the formation of A.fumigatus biofilm.