Effects of dietary mulberry leaves on growth, production performance, gut microbiota, and immunological parameters in poultry and livestock: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the effects of dietary mulberry leaves on the growth, production performance, gut microbiota, and immunological parameters of poultry and livestock. METHODS: The PubMed, Embase, and Scopus databases were systematically analyzed to identify pertinent studies up to December 2022. The effects of mulberry leaf diet was assessed using the weighted mean difference, and the 95% confidence interval was calculated using a random-effects model. RESULTS: In total, 18 studies that sampled 2,335 poultry and livestock were selected for analysis. Mulberry leaves improved the average daily gain and reduced the feed/meat ratio in finishing pigs, and the average daily gain and average daily feed intake in chicken. In production performance, mulberry leaves lowered the half carcass weight, slaughter rate, and loin eye area in pigs, and the slaughter rate in chickens. Regarding meat quality in pigs, mulberry leaves reduced the cooked meat percentage, shear force, crude protein, and crude ash, and increased the 24 h pH and water content. In chickens, it increased the drip loss, shear force, 45 min and 24 h pH, crude protein, and crude ash. Mulberry leaves also affect the abundances of gut microbiota, including Bacteroides, Prevotella, Megamonas, Escherichia-Shigella, Butyricicoccus, unclassified Ruminococcaceae, Bifidobacterium, Lactobacillus, and Escherichia coli in poultry and livestock. Mulberry leaves at different doses were associated with changes in antioxidant capacity in chickens, and immune organ indexes in pigs. With respect to egg quality, mulberry leaves at different doses improved the shell strength, yolk color, eggshell thickness, and eggshell weight. However, moderate doses diminished the egg yolk ratio and the egg yolk moisture content. CONCLUSION: In general, dietary mulberry leaves improved the growth, production performance, and immunological parameters in poultry and livestock, although the effects varied at different doses.

Circ-SATB2 (hsa_circ_0008928) and miR-150-5p are regulators of TRIM66 in the regulation of NSCLC cell growth and metastasis of NSCLC cells via the ceRNA pathway.

Circular RNA (circRNA) was an important modulator and potential molecular target of nonsmall cell lung cancer (NSCLC). CircSATB2 was reported to be upregulated in NSCLC. However, the role and mechanism of circSATB2 in NSCLC progression remain to be illustrated. The RNA and protein expression was detected by quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry assay. Cell counting kit-8, cell colony formation, and 5-ethynyl-2'-deoxyuridine assays were applied to assess cell growth. The migrated and invaded cells were examined by transwell assay. Flow cytometry was performed to measure apoptotic cells. The interaction among circSATB2, microRNA-150-5p (miR-150-5p), and tripartite motif-containing protein 66 (TRIM66) was identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. An in vivo experiment was conducted to investigate the effect of circSATB2 on tumor growth. CircSATB2 expression was highly expressed in NSCLC tissues and cell lines. CircSATB2 and TRIM66 silencing both suppressed NSCLC cell growth, migration, and invasion whereas promoted NSCLC cell apoptosis. CircSATB2 acted as a molecular sponge for miR-150-5p, and miR-150-5p interacted with the 3' untranslated region (3'UTR) of TRIM66. Moreover, circSATB2 knockdown-induced effects were partly reversed by TRIM66 overexpression in NSCLC cells. Besides, cirSATB2 expression was negatively correlated with miR-150-5p level and positively correlated with TRIM66 level in NSCLC tumor tissues. CircSATB2 knockdown blocked xenograft tumor growth in vivo. In summary, this study verified that circSATB2 stimulated NSCLC cell malignant behaviors by miR-150-5p/TRIM66 pathway, providing a possible circRNA-targeted therapy for NSCLC.

Influence of meteorological factors on open biomass burning at a background site in Northeast China.

Biomass burning (BB) is a very important emission source that significantly adversely impacts regional air quality. BB produces a large number of primary organic aerosol (POA) and black carbon (BC). Besides, BB also provides many precursors for secondary organic aerosol (SOA) generation. In this work, the ratio of levoglucosan (LG) to organic carbon (OC) and the fire hotspots map was used to identify the open biomass burning (OBB) events, which occurred in two representative episodes, October 13 to November 30, 2020, and April 1 to April 30, 2021. The ratio of organic aerosol (OA) to reconstructed PM2.5 concentration (PM2.5*) increased with the increase of LG/OC. When LG/OC ratio is higher than 0.03, the highest OA/PM2.5* ratio can reach 80%, which means the contribution of OBB to OA is crucial. According to the ratio of LG to K+, LG to mannosan (MN) and the regional characteristics of Longfengshan, it can be determined that the crop residuals are the main fuel. The occurrence of OBB coincides with farmers' preferred choices, i.e., burning biomass in "bright weather". The "bright weather" refers to the meteorological conditions with high temperature, low humidity, and without rain. Meteorological factors indirectly affect regional biomass combustion pollution by influencing farmers' active choices.

Severe photochemical pollution formation associated with strong HONO emissions from dew and guttation evaporation.

The unknown daytime source of HONO has been extensively investigated due to unexplained atmospheric oxidation capacity and current modelling bias, especially during cold seasons. In this study, abrupt morning increases in atmospheric HONO at a rural site in the North China Plain (NCP) were observed almost on daily basis, which were closely linked to simultaneous rises in atmospheric water vapor content and NH3 concentrations. Dew and guttation water formation was frequently observed on wheat leaves, from which water samples were taken and chemically analyzed for the first time. Results confirmed that such natural processes likely governed the daily nighttime deposition and daytime release of HONO and NH3, which have not been considered in the numerous HONO budget studies investigating its large missing daytime source in the NCP. The dissolved HONO and NH3 in leaf surface water droplets reached 1.4 and 23 mg L-1 during the morning on average, resulting in averaged atmospheric HONO and NH3 increases of 0.89 ± 0.61 and 43.7 ± 29.3 ppb during morning hours, with relative increases of 186 ± 212 % and 233 ± 252 %, respectively. The high atmospheric oxidation capacity contained within HONO was stored in near surface liquid water (such as dew, guttation and soil surface water) during nighttime, which prevented its atmospheric dispersion after sunset and protected it from photodissociation during early morning hours. HONO was released in a blast during later hours with stronger solar radiation, which triggered and then accelerated daytime photochemistry through the rapid photolysis of HONO and subsequent OH production, especially under high RH conditions, forming severe secondary gaseous and particulate pollution. Results of this study demonstrate that global ecosystems might play significant roles in atmospheric photochemistry through nighttime dew formation and guttation processes.

Circulating exosomal microRNA-4497 as a potential biomarker for metastasis and prognosis in non-small-cell lung cancer.

Circulating exosomal microRNAs (miRNAs) have shown great potential for the diagnosis, prognosis, and treatment monitoring of patients with non-small-cell lung cancer (NSCLC). Our main purpose was to determine the clinical value of serum exosomal miR-4497 as a new non-invasive biomarker for NSCLC. The exoRNeasy Kit (QIAGEN, Hilden, Germany) was used to isolate exosomes and exoRNA from the serum of 84 patients with NSCLC (NSCLC group), 30 patients with benign lung lesion (BLL group), and 47 healthy controls. Six serum exosomal miRNAs (Let-7b-5p, miR-122-5p, miR-155-5p, miR-223-3p, miR-320c, and miR-4497) were selected as candidate miRNAs and analyzed using real-time qPCR, among which miR-4497 displayed the most striking differences. Exosomal miR-4497 expressed significantly lower in NSCLC than in BLL patients and healthy controls (P < 0.001). Further investigation showed that miR-4497 was negatively correlated with the malignant characteristics of tumors (tumor size, tumor-node-metastasis [TNM] stage, and distant metastasis) and was an independent tumor suppressor (P < 0.05). According to receiver operating characteristic (ROC) analysis, exosomal miR-4497 independently exhibited excellent diagnostic efficacy, which could be improved by combining it with traditional markers (for identifying tumor size, the area under the curve [AUC] = 0.761; TNM stage, AUC = 0.878; distant metastasis, AUC = 0.895; all P < 0.001). Moreover, longitudinal analysis revealed that exosomal miR-4497 levels increased after chemoradiotherapy (P < 0.001). According to the survival analysis, poor overall survival (OS) and disease-free survival (DFS) were associated with low exosomal miR-4497 levels (P < 0.05). Moreover, exosomal miR-4497 was an independent protective factor affecting DFS (hazard ratio = 0.190, P = 0.009) in the Cox proportional hazards model. Therefore, serum exosomal miR-4497 can be used as a potential biomarker to identify NSCLC and healthy individuals or BLL patients for early screening or as a biomarker for staging and grading, prognosis, and monitoring recurrence, metastasis, and the therapeutic effects in patients with NSCLC.

Chemical composition, oxidative potential and identifying the sources of outdoor PM2.5 after the improvement of air quality in Beijing.

Air pollution poses a serious threat to human health. The implementation of air pollution prevention and control policies has gradually reduced the level of atmospheric fine particles in Beijing. Exploring the latest characteristics of PM2.5 has become the key to further improving pollution reduction measures. In the current study, outdoor PM2.5 samples were collected in the spring and summer of Beijing, and the chemical species, oxidative potential (OP), and sources of PM2.5 were characterized. The mean PM2.5 concentration during the entire study period was 41.6 ± 30.9 µg m-3. Although the PM2.5 level in summer was lower, its OP level was significantly higher than that in spring. SO42-, NH4+, EC, NO3-, and OC correlated well with volume-normalized OP (OPv). Strong positive correlations were found between OPv and the following elements: Cu, Pb, Zn, Ni, As, Cr, Sn, Cd, Al, and Mn. Seven sources of PM2.5 were identified, including traffic, soil dust, secondary sulfate, coal and biomass burning, oil combustion, secondary nitrate, and industry. Multiple regression analysis indicated that coal and biomass combustion, industry, and traffic were the main contributors to the OPv in spring, while secondary sulfate, oil combustion, and industry played a leading role in summer. The source region analysis revealed that different pollution sources were related to specific geographic distributions. In addition to local emission reduction policies, multi-provincial cooperation is necessary to further improve Beijing's air quality and reduce the adverse health effects of PM2.5.

[Characteristics and Impact Factors of Number Concentration of Primary Biological Aerosol Particles in Beijing].

Primary biological aerosol particles (PBAP) are an important part of ambient aerosols. Both living and dead organisms not only influence human health and air quality but also play important roles in regulating certain atmospheric processes and affect the hydrological cycle and climate change. In this study, flow cytometry (FCM) was utilized in combination with the simultaneous use of permeant (SYBR Green I) and impermeant (propidium iodide, PI) nucleic acid fluorescent staining to detect and quantify the viable and dead airborne biological particles. At the same time, based on this method, the dead/viable PBAP in a Beijing urban area was detected and quantified. Moreover, the influence of environmental factors on the concentrations of primary biological aerosol particles was illuminated. The results showed that the media number concentration of dead and alive PBAP in the Beijing urban area during summer (1.03×106 m-3 and 7.43×105 m-3, respectively) were higher than those during winter (7.34×105 m-3and 6.18×105 m-3, respectively). Statistical analysis showed that there was no significant correlation between PBAP number concentration and environmental factors, i.e., meteorological conditions and air quality, showing a weak positive correlation with temperature and humidity and weak negative correlations with O3, maximum wind speed, and sunshine duration. The number concentration of PBAP was weakly correlated with the mass concentration of PM2.5 but positively correlated with that of coarse particulate matter (PM2.5-10). Both stable weather and dust transport could increase the number concentration of PBAP in Beijing.

Nesfatin-1 alleviated lipopolysaccharide-induced acute lung injury through regulating inflammatory response associated with macrophages modulation.

Acute lung injury (ALI) is a continuum of lung changes associated with uncontrolled excessive lung inflammation. However, the pathogenesis of ALI is still complicated and effective clinical pharmacological management is required. Various signaling pathways are involved in the inflammatory responses of ALI. Here, we aimed to explore the role of nesfatin-1, an amino-acid peptide with anti-inflammatory action, in an LPS-induced ALI mice model, and its role in regulating macrophages in response to LPS stimulation in vitro. This was to clarify the underlying mechanisms of regulating the inflammatory response in the development of ALI. The results show that nesfatin-1 expression was downregulated in the lung tissues of ALI mice compared to control mice. Nesfatin-1 treatment ameliorated the inflammatory response and lung tissue damage in LPS-induced ALI in mice. In vitro studies showed that nesfatin-1 attenuated the generation and release of proinflammatory cytokines interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in LPS-induced RAW 264.7 cells. Nesfatin-1 also inhibited reactive oxygen species production and improved superoxide dismutase (SOD) activity in LPS-induced RAW 264.7 cells. These findings suggest that nesfatin-1 exerted a crucial role in regulating the LPS-mediated activation of M1 macrophages. Further mechanism investigations indicated that nesfatin-1 inhibited the activation of p38 MAPK/c-Jun and NF-κB pathways in LPS-induced RAW 264.7 cells, as evidenced by decreased expression levels of p-p38, p-c-Fos, and p-p65. Overall, nesfatin-1 alleviated LPS-induced ALI, which might be attributed to regulating inflammatory response through macrophages modulation.

STIM2 promotes the invasion and metastasis of breast cancer cells through the NFAT1/TGF-ß1 pathway.

A large amount of evidence indicates that the abnormal activation of multiple signal transduction pathways in cells is closely related to the occurrence and development of tumors. TGF-ß and NFAT1 signaling pathways can inhibit cell proliferation and promote apoptosis in the early stage of breast cancer, but with the increase of tumor malignancy, the two appear to promote tumor progression and deterioration. Therefore, the study of the relationship between STIM2 and NFAT1/TGF-ß1 is helpful for the discovery and treatment of breast cancer, which is of great significance for improving the survival rate of breast cancer patients. This article focuses on the effect of STIM2 molecules on breast cancer cell migration through the NFAT1/ TGF-ß1 pathway and discusses the regulatory mechanism of STIM2 affecting breast cancer cell migration. Experimental data shows that the positive rate of breast cancer NFAT1 is 54%, which is significantly lower than that of benign breast Tissue 85%; the positive expression rate of TGF-ß1 in benign breast tissue is 85%, and the positive expression rate in breast cancer tissue is 49%. The results show that STIM2 protein can promote the invasion and metastasis of breast cancer cells through the NFAT1 / TGF-ß1 pathway.

The effect of miR-138 on the proliferation and apoptosis of breast cancer cells through the NF-κB/VEGF signaling pathway.

The analyze the effect of miR-138 on the proliferation and apoptosis of breast cancer cells through the NF-κB/VEGF signaling pathway is the Objective of this experiment. For this aim, the endometrial stem breast cancer cell line MCF-7 was cultured in vitro, and the overexpression mimic miR-138 mimics and the inhibitor anti-miR-138 were transfected into the endometrial stem breast cancer cell line MCF-7, which was set to overexpress miR-138 group and interfere with miR-138, and set up negative control of overexpression and negative control of inhibitor. Observe the cell proliferation and apoptosis ability of each group, and the changes in tumor necrosis factor-α (TNF-α), interleukin 1ß, 6, 18 (IL-1ß, IL-6, IL-18) levels, and compare the Bax of each group, NF-κB, VEGF protein expression level. Results showed that the proliferation ability of the miR-138 overexpression group was significantly lower than that of the miR-138 overexpression control group (P<0.05); the proliferation ability of the miR-138 interference group was significantly higher than that of the miR-138 interference control group (P<0.05). The apoptosis rate, caspase-3 and caspase-9 expression levels of the miR-138 overexpression group were significantly higher than those of the miR-138 overexpression control group (P<0.05);  the apoptosis rate, caspase-3 and caspase-9 expression levels of the miR-138 interference group were significantly lower than those of the miR-138 interference control group (P<0.05). The expression levels of IL-1 ß, IL-6, IL-18 and TNF - α in the miR-138 overexpression group were significantly lower than those in the miR-138 overexpression control group (P < 0.05). The protein expression levels of Bax, NF-κB and VEGF in the miR-138 overexpression group were significantly lower than those in the miR-138 overexpression control group (P < 0.05); the protein expression levels of Bax, NF-κB and VEGF in the miR-138 interference group were significantly higher than those in the miR-138 interference control group (P <0.05). The proliferation ability of the miR-138 overexpression group was significantly lower than that of the miR-138 overexpression control group (P < 0.05); the proliferation ability of the miR-138 + NF-κB overexpression group was significantly higher than that of the miR-138 overexpression group (P<0.05). The apoptosis rate of the miR-138 + NF-κB overexpression group was significantly lower than that of the miR-138 overexpression group (P < 0.05). Then MiR-138 can significantly inhibit the proliferation of breast cancer cells, promote apoptosis, and regulate the expression of inflammatory factors in the cells. It is speculated that the related mechanism may be related to the negative regulation of the NF-κB/VEGF signaling pathway.

Impacts and mechanisms of metabolic reprogramming of tumor microenvironment for immunotherapy in gastric cancer.

Metabolic disorders and abnormal immune function changes occur in tumor tissues and cells to varying degrees. There is increasing evidence that reprogrammed energy metabolism contributes to the development of tumor suppressive immune microenvironment and influences the course of gastric cancer (GC). Current studies have found that tumor microenvironment (TME) also has important clinicopathological significance in predicting prognosis and therapeutic efficacy. Novel approaches targeting TME therapy, such as immune checkpoint blockade (ICB), metabolic inhibitors and key enzymes of immune metabolism, have been involved in the treatment of GC. However, the interaction between GC cells metabolism and immune metabolism and how to make better use of these immunotherapy methods in the complex TME in GC are still being explored. Here, we discuss how metabolic reprogramming of GC cells and immune cells involved in GC immune responses modulate anti-tumor immune responses, as well as the effects of gastrointestinal flora in TME and GC. It is also proposed how to enhance anti-tumor immune response by understanding the targeted metabolism of these metabolic reprogramming to provide direction for the treatment and prognosis of GC.

Molecular detection and genetic characterization of small rodents associated Bartonella species in Zhongtiao Mountain, China.

The prevalence and molecular characteristics of Bartonella infections in small rodents in the Zhongtiao Mountain, China have been explored. In this study, the liver, spleen and kidney tissues of captured rodents were used for Bartonella spp. detection and identification by combination of real-time PCR of transfer-mRNA (ssrA) gene and traditional PCR and sequencing of citrate synthase (gltA) gene. It was shown that 49.52% of the rodents (52/105) were positive for Bartonella spp.. The infection rate in different gender (χ2 = 0.079, P = 0.778) and tissues (χ2 = 0.233, P = 0.890) of small rodents did not have statistical difference, but that in different small rodents (Fisher's exact test, P < 0.001) and habitats (χ2 = 5.483, P = 0.019) had statistical difference. And, the sequencing data suggests that Bartonella sequences (n = 31) were identified into three species, including 14 of B. grahamii, 3 of B. queenslandensis and 14 of unknown Bartonella species. Phylogenetic analysis showed that B. grahamii sequences were clustered with the isolates from South Korea and China, and B. queenslandensis sequences were mainly closely related to the isolates from China and Thailand. The genetic diversity analysis showed that B. grahamii and B. queenslandensis sequences exhibited noticeable intraspecies diversity. Taken together our data demonstrates the high prevalence and genetic diversity of Bartonella infections in small rodents in the Zhongtiao Mountain, especially a potential novel Bartonella specie was detected, which could benefit the prevention and control of rodent-Bartonella species in this area.

Changes in ammonia and its effects on PM2.5 chemical property in three winter seasons in Beijing, China.

NH3, SO2, NOx and the inorganic ions of PM2.5 in winter 2009, 2014 and 2016 were examined to investigate the change in NH3 and aerosol chemistry in Beijing, China. NH3 concentrations showed an increase by 59% on average, in contrast to the decrease of SO2 by 63% from winter 2009 to 2016. The mean mass ratio of NH3/NHx was 0.83 ± 0.12 in 2016, which is higher than those obtained in 2009 and 2014, implying more NHx remaining as free NH3 in 2016 winter. Our findings suggest that vehicles exhaust emissions are an important NH3 source in urban central atmosphere of Beijing in winter. Despite the observed NOx presenting declining trends from 2014 to 2016, nitrate concentrations even exhibited a significant increasing trend, which may be largely attributable to high NH3 levels. An in-depth analysis of measured NH3 and aerosol species in a heavy pollution episode in December 2016, combined with the acidity predicted by ISORROPIA II model demonstrated abundant NH3 most of the time in air, where NH3 is not only a precursor for NH4+ but also effect the neutralization of SO42- and NO3- in PM2.5. With high RH and low photochemical activity, elevated NO3- concentration was attributed to an enhanced heterogeneous conversion of NOx to HNO3 to form NH4NO3 in pollution transport stage. The decrease in NOx from high level and the increase in NH3, with peaks of SO42- occurring were observed in pollution cumulative stage. The aqueous-phase oxidation of SO2 by NO2 to sulfate might play an important role with high pH values. Our results suggested that the simultaneous control of NH3 emissions in conjunction with SO2 and NOx emissions would be more effective in reducing particulate matter PM2.5 formation.

Dust-Dominated Coarse Particles as a Medium for Rapid Secondary Organic and Inorganic Aerosol Formation in Highly Polluted Air.

Secondary aerosol (SA) frequently drives severe haze formation on the North China Plain. However, previous studies mostly focused on submicron SA formation, thus our understanding of SA formation on supermicron particles remains poor. In this study, PM2.5 chemical composition and PM10 number size distribution measurements revealed that the SA formation occurred in very distinct size ranges. In particular, SA formation on dust-dominated supermicron particles was surprisingly high and increased with relative humidity (RH). SA formed on supermicron aerosols reached comparable levels with that on submicron particles during evolutionary stages of haze episodes. These results suggested that dust particles served as a medium for rapid secondary organic and inorganic aerosol formation under favorable photochemical and RH conditions in a highly polluted environment. Further analysis indicated that SA formation pathways differed among distinct size ranges. Overall, our study highlights the importance of dust in SA formation during non-dust storm periods and the urgent need to perform size-resolved aerosol chemical and physical property measurements in future SA formation investigations that are extended to the coarse mode because the large amount of SA formed thereon might have significant impacts on ice nucleation, radiative forcing, and human health.

[Effect of acetabular tilt angle on acetabular version in adults with developmental dysplasia of the hip].

Objective: To investigate the difference in acetabular tilt angle (ATA) between adults with deve-lopmental dysplasia of the hip (DDH) and normal adults and the effect of ATA on acetabular version. Methods: Between February 2009 and October 2015, 31 adult female patients with DDH (39 hips) (DDH group) and 31 female patients with osteoarthritis of the knee (31 hips) who had no history of hip disease (control group) were included in this study. The average age was 39 years (range, 18-59 years) in the DDH group, and was 69 years (range, 52-79 years) in control group. The morphometric parameters of the acetabulum including ATA, acetabular anteversion angle (AAA), acetabular inclination angle (AIA), acetabular cranial anteversion angle (ACAA), and acetabular sector angle (ASA) were mea- sured by CT reconstruction; The ASA was used as an index for acetabular coverage of the femoral head. The correlation between ATA and other parameters was analyzed using Pearson correlation analysis. Results: The values of ATA, AAA, and AIA of the DDH group were significantly larger than those of the control group ( P<0.05). The ASA in all directions was significantly decreased in the DDH group when compared with the values in the control group ( P<0.05). There was no significant difference in ACAA between two groups ( t=1.918, P=0.523). The ATA was positively correlated with AAA and ACAA in the DDH group ( r=0.439, P=0.001; r=0.436, P=0.002), but there was no correlation between ATA and AIA ( r=0.123, P=0.308). In the control group, the ATA was not correlated with AAA, ACAA, and AIA ( r=-0.004, P=0.724; r=-0.079, P=0.626; r=-0.058, P=0.724). Regarding acetabular coverage of the femoral head, the ATA and AAA were correlated negatively with anterior ASA ( P<0.05) and positively with posterior ASA ( P<0.05), but had no correlation with superior ASA ( P>0.05) in the DDH group; AIA was correlated negatively with anterior ASA and superior ASA ( P<0.05) and had no correlation with posterior ASA ( r=-0.092, P=0.440). In the control group, there was no correlation between ATA and ASA in any direction ( P>0.05). In the DDH group, defects of the acetabular anterior wall, lateral wall, and posterior wall were observed in 18 hips (46.2%), 15 hips (38.5%), and 6 hips (15.3%), respectively. ATA value of the posterior wall defect [(15.70±10.00)°] was significantly smaller than those of the acetabular anterior wall and lateral wall defects [(22.91±5.06)° and (21.59±3.81) °] ( P<0.05), but no signficant difference was found between anterior wall and lateral wall defects ( P>0.05). Conclusion: ATA will influence acetabular version in DDH. The anterior rotation of the acetabular fragment during periacetabular osteotomies is an anatomically reasonable maneuver for hips with anterolateral acetabular defect, while the maneuver should be avoided in hips with posterior acetabular defect.

Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways.

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient and antioxidant and has been reported to exert potent immunosuppressive effects. However, the therapeutically potential of PQQ on rheumatoid arthritis (RA) has not been explored. In the present study, the anti-inflammatory effects of PQQ were investigated in interleukin (IL)-1ß-treated SW982 cells, a RA-like fibroblast-like synoviocytes (FLSs) injury model. Our observations showed that pretreatment with PQQ significantly inhibited the expression of matrix metalloproteinase (MMP)-1 and MMP-3 and suppressed the production of proinflammatory mediators such as TNF-α and IL-6 in IL-1ß-treated SW982 cells. The nuclear translocation of nuclear factor kappa B (NF-κB) and the phosphorylation level of p65, p38, and JNK MAP kinase pathways were also inhibited by PQQ in IL-1ß-stimulated SW982 cells. To further confirm the therapeutic effects of PQQ on RA in vivo, a collagen-induced arthritis (CIA) model was used. Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of RA.

[Screening of Molluscacidal Microorganisms against Oncomelania hupensis and Their Effect].

Fifteen soil samples were collected from Oncomelania hupensis culture pond in Miluo Schistosomiasis Control and Prevention Base, Hunan Province. Four strains of bacteria were identified to have molluscacidal effects, numbered as B8, B27, B36 and B59. Compared with the fermentation broth groups and bacteria suspension groups, the fermentation supernatant groups of the four strains showed the strongest molluscacidal effect. The fermentation supernatant of B59 strain showed the best molluscacidal effect, with snail mortalit of 73.3% and 96.7% at 48 h and 72 h of treatment, respectively. SDS-PAGE revealed no proteins in fermentation supernatant, fermentation broth and bacteria suspension of B59 strain. Molecular phylogenetic analysis based on ITS sequence showed that the ITS sequence of strain B59 (accession No. KP146144) was 100% homologous to that of the same fragment of Bacillus cereus (accession No. CP001746).

Sam68 Promotes NF-κB Activation and Apoptosis Signaling in Articular Chondrocytes during Osteoarthritis.

OBJECTIVES: To investigate the expression of Sam68 in articular cartilage of knee osteoarthritis (OA) and the relationship between Sam68 and NF-κB activation and apoptosis signaling in OA articular chondrocytes. METHODS: Sam68 expression in normal and osteoarthritic cartilage was assessed by immunohistochemistry and RT-PCR on both meniscal/ligamentous injury (MLI)-induced OA rat model and the clinical human OA cartilage tissues. Sam68 expression in chondrocytes under tumor necrosis factor-alpha (TNF-α) stimuli was also assessed by immunoblot. Inhibiting Sam68 in chondrocytes under TNF-α stimuli was conducted using small interfering RNA (siRNA) and its influence on the expression of apoptotic marker and catabolic genes was examined by immunoblot. The mechanism of how Sam68 stimulates NF-κB activity was determined by co-immunoprecipitation and immunoblot analysis of nuclear and cytoplasmic fractions of TNF-α-treated chondrocytes for p65 and Sam68. RESULTS: Sam68 expression was increased in OA cartilage tissues and chondrocytes under TNF-α stimuli. Inhibition of Sam68 by siRNA significantly decreased the expression of apoptotic markers (cleaved caspase-3 and cleaved PARP) in chondrocytes following TNF-α-stimulation. Sam68 knockdown suppressed Iκ-B degradation and p65 nuclear transportation in TNF-α-treated chondrocytes, indicating a suppressed NF-κB activation. Upon TNF-α exposure, the nuclear transportation of Sam68 and its interaction with p65 was detected in chondrocytes. Furthermore, Sam68 knockdown also alleviated the TNF-α-induced catabolic marker (MMP13, ADAMTS5, iNOS and IL-6) expression. CONCLUSIONS: The highly expressed Sam68 promotes NF-κB signaling activation, catabolic gene expression and cellular apoptosis in TNF-α-treated chondrocytes, which may provide better insights into the pathophysiology of OA and a potential target for its treatment.

KPNA2 Contributes to the Inflammatory Processes in Synovial Tissue of Patients with Rheumatoid Arthritis and SW982 Cells.

Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the function and possible mechanisms of KPNA2 involved in rheumatoid arthritis (RA). Western blotting and immunohistochemistry showed the protein expression of KPNA2 increased in synovial tissue of RA patients compared with the healthy controls. Double immunofluorescent staining indicated that KPNA2 co-localized with T cells, macrophage-like synoviocytes, fibroblast-like synoviocytes, and neutrophils in synovial tissue of RA patients. Moreover, the expression of KPNA2 in SW982 cells was increased in a time-dependent manner in response to TNFα stimulation. Both Western blotting and immunofluorescent staining assay revealed the co-localization of KPNA2 and P65 and their translocation from cytoplasma in TNFα-treated SW982 cells. Furthermore, knocking down the expression of KPNA2 by siRNA inhibited TNFα-induced expression of IL-6, MMP-1, and MMP-13 and, more importantly, decreased the P65 phosphorylation in SW982 cells. We therefore suggested that KPNA2 may play a key role in the inflammation process of RA via NF-κB P65 signal transduction pathway.

KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis.

OBJECTIVE: Karyopherin alpha 2 (KPNA2) is a member of the importin α family, which acts as an adaptor to deliver P65 to the nucleus by recognizing the classic nuclear localization signal (NLS) of the cargo protein, and which has been reported as being involved in the pathogenesis of many diseases. This study was undertaken to determine the expression and possible functions of KPNA2 in osteoarthritis (OA). METHODS: KPNA2 expression in cartilage tissues of OA patients and normal controls was detected by RT-PCR and immunohistochemistry. SW1353 cells were stimulated with IL-1ß to establish the chondrocyte injury model in vitro. The expression of KPNA2 and catabolic genes in IL-1ß-treated SW1353 cells were determined by Western blot. The interaction between KPNA2 and P65 was analyzed by co-immunoprecipitation, the subcellular distribution and transportation of P65 were detected by the subcellular fractionation followed by immunoblot analysis and immunofluorescence. Furthermore, we used RNA interference to analyze the role of KPNA2 in IL-1ß-induced P65 nuclear importation and MMP13, ADAMTS-5 expression in SW1353 cells. RESULTS: Cartilage expression of KPNA2 was higher in patients with OA compared with normal controls and mainly locating in chondrocytes. In IL-1ß-treated SW1353 cells, up-regulation of KPNA2 was accompanied by the elevated expression of the catabolic marker protein levels, including MMP13 and ADAMTS-5, and increased NF-κB P65 nuclear importation. Knock-down of KPNA2 resulted in decreased catabolic marker protein levels in IL-1ß-treated SW1353 cells. KPNA2 interacted with p65, and loss of KPNA2 caused decreased nuclear translocation of the active p50/p65 NF-κB complex. CONCLUSIONS: These findings suggested that KPNA2 may promote NF-κB activation via facilitating P65 nuclear transportation, and thus subsequently accelerate the catabolic events of osteoarthritis.