Tumour necrosis factor stimulated gene 6 intrinsically regulates PD-L1 expressions in breast cancer cells,leading to modulation of tumour microenvironment

Recent studies have shown that tumour cells express tumour necrosis factor-inducible gene 6 (TSG-6) and its protein, which is known to play a key role in regulating excessive immune responses and proliferation and growth of mesenchymal stem cells (MSCs). It has not been confirmed whether the inhibition of TSG-6 for tumour cells can suppress tumour cell growth and regulate the activation of immune cells in the tumour microenvironment (TME). TSG-6-specific small interfering RNA was transfected into canine and human breast cancer cells (CIPp, CIPm and BT-20). TSG-6-down-regulated (siTSG-6) cells showed decreased cell proliferation, migration, and invasion abilities. Decreased mRNA expressions of NF-κB, STAT3 and Sox2, confirming that TSG-6 is an upper factor governing tumour growth and metastasis. Notably, siTSG-6 cells showed significantly decreased expression levels of CD44 and PD-L1. Direct and indirect co-culture of canine peripheral blood mononuclear cells (cPBMCs) and the siTSG-6 cells showed significant activation in M1 type macrophages and cytotoxic T cells. They also showed a tendency to decrease in the expression of CTLA-4 and increase in the expression of PD-1. In conclusion, this study suggests that the down-regulation of TSG-6 in breast cancer cells could not only suppress tumour growth and metastasis, and but also regulate TME. Since modulation of immune checkpoint proteins occurs in both tumour cells and immune cells, inhibiting TSG-6 and its protein within the TME could be novel therapeutic target for anticancer treatment.     

Enzyme studies with the livers of chicks fed semi‐synthetic diets containing crystalline amino acids and diammonium citrate

The levels of glutamate dehydrogenase [NAD(P)], (GDH), aspartate trans‐aminase (AspT) and alanine transaminase (AlT) were measured in livers from chicks fed on a semi‐synthetic diet containing crystalline essential amino acids as the sole nitrogen source (diet A). The effects of a supplement of 12.0% glutamic acid (diet H) or 11.07% diammonium citrate (DAC) (diet B) or 12.0% glutamic acid plus 1.0% proline with an additional 0.6% glycine (diet C) on these enzymes were studied and the results compared with the levels found for control chicks given a typical diet based on cereal protein (diet J). The abilities of livers from chicks given diets A, B and C to synthesise [14C] glutamic acid from [14C]2‐oxoglutaric acid and diammonium citrate (DAC) were assessed.

The levels of GDH, AspT and AlT found in the livers of chicks given the control diet were 54.1, 966 and 123.7 units/mg protein respectively. Non‐essential nitrogen added as glutamic acid or as DAC did not cause induction of the enzymes studied above control levels. Glutamic acid (diets H and B) caused a depression of GDH levels (37.4 and 38.9 units/mg protein respectively) but had no effect on AspT and AlT compared with the controls, whereas DAC caused a decrease in AlT (43.9 units/mg protein) but had no effect on AspT and GDH; diet A depressed AlT and AspT levels (64.4 and 735 units/mg protein respectively).

The livers of chicks given diets A, C and B varied in their ability to synthesise glutamic acid, 39.3%, 31.9% and 24.0% respectively of the radioactivity being recovered as glutamic acid.     

Parameter estimates for direct and maternal genetic effects on yearling, eighteen-month, and slaughter weights of Korean native cattle

Data collected by the National Livestock Research Institute of the Rural Development Administration of Korea were used to estimate genetic parameters for yearling (YWT, n = 5,848), 18-mo (W18, n = 4,585), and slaughter (SWT, n = 2,279) weights for Korean Native cattle. Nine animal models were used to obtain REML estimates of genetic parameters: DP-2 included genetic, uncorrelated dam, and residual random effects; DQ-2 included genetic, sire x region x year-season interaction, and residual random effects; DPQ-2 was based on DQ-2 but included both interaction and dam effects; DMP-2 was based on DP-2 but with dam effect partitioned to include maternal genetic and permanent environmental effects; and DMPQ-2 was based on DMP-2 but also included sire interaction effects. Those five models included two fixed factors: region x year-season and age of dam x sex effects. Models DP-3, DQ-3, DPQ-3, and DMPQ-3 were based on DP-2, DQ-2, DPQ-2, and DMPQ-2 but included as a third fixed factor whether or not identification of the sire was known. Estimates of heritability with DMPQ-3 for YWT, with DPQ-3 for W18 and SWT when analyzed with single-trait analyses were .14, .11, and .17, respectively, and were nearly the same with bivariate analyses. Estimate of maternal heritability for YWT from single-trait analysis was .04, with estimates for other traits near zero. For bivariate analyses, the estimate for YWT was .01. With single trait analysis, estimate of the direct-maternal genetic correlation for YWT was negative (-.81). Estimates of direct genetic correlations between YWT and W18, YWT and SWT, and W18 and SWT were .99, 1.00, and .97, respectively. Estimates of environmental correlations varied from .60 to .81; the largest was between W18 and SWT. Including a fixed factor for whether sire identification was missing or not missing reduced the estimate of heritability for slaughter weight. The results suggest that the sire x region x year-season interaction is important for yearling weight and may be needed in a model for slaughter weight. Maternal effects may be of slight importance for yearling weight but of no importance for W18 and SWT. Models for national cattle evaluations for Korean Native cattle for YWT should be considered that include maternal genetic and permanent environmental as well as sire x region x year-season interaction effects, but those effects seem not to be needed for models for W18 and SWT. Not much reranking of sires occurred when ranked was based on the different models for W18 and SWT.     

Effect of intravenous mannitol upon the resistive index in complete unilateral renal obstruction in dogs

Some studies have shown that relative to baseline, the renal resistive index (RI) remains unchanged in nonobstructed kidneys and increases in obstructed kidneys after administration of furosemide. To our knowledge, the effect of mannitol administration on the renal RI of dogs has not been reported. We evaluated the renal RI in 16 kidneys in 8 young adult dogs after administration of mannitol. The mean RI decreased significantly from baseline (P < .01). Additionally, left complete ureteral obstruction wasinduced in 5 dogs. Evaluation by Doppler ultrasonography was performed for 5 days. On the 5th day, Doppler examination was repeated at 30 and 60 minutes after administration of mannitol to obstructed dogs. After induction of left ureteral obstruction, the RI of the left kidney increased significantly over 5 consecutive days. Administration of mannitol decreased the RI in the nonobstructed contralateral kidneys, and thus the RI difference between obstructed and nonobstructed kidneys was increased above normal (P < .001). In conclusion, administration of mannitol may be useful as another diuretic agent to identify unilateral ureteral obstruction on Doppler sonographic examination.     

The Epidemiology and Characteristics of Q fever and Co‐infections with Scrub Typhus,Murine Typhus or Leptospirosis in Taiwan: A Nationwide Database Study

Q fever (QF) is a worldwide zoonosis associated with outbreaks. Only a few nationwide studies regarding the surveillance and epidemiology of human QF have been reported. Although QF is endemic in Taiwan, a nationwide database investigation of the epidemiology and characteristics of QF and its associations with scrub typhus (ST), murine typhus (MT) and leptospirosis (LS) has never been reported. We analysed nationwide databases of suspected QF, ST, MT and LS cases from October 2007 to December 2014 obtained from the Centers for Disease Control, Taiwan. A total of 468 (4.2%) QF cases were identified among 11 109 suspected QF cases. QF cases were mainly distributed in the southern and Kaohsiung–Pingtung regions but rarely in the eastern region. Compared to non‐QF cases, QF cases had significantly higher percentages of males (88.7 versus 66.2%) and high‐risk occupations (farming, animal husbandry or veterinary medicine) (16.2 versus 10.5%). But the percentages of specific animal contact, including cattle (0.6 versus 0.8%) and goats (0.9 versus 1.0%), were low in both. The majority of suspected QF cases (89.4%) were simultaneously suspected with ST, MT or LS, and the combinations of suspected diseases differed between regions. The number of suspected QF cases from the eastern region decreased since 2009, which was not observed in other regions. A total of 1420 (12.8%) cases had confirmed diseases, including QF (453, 4.1%), QF+ST (7, 0.06%), QF+MT (4, 0.04%), QF+LS (4, 0.04%), MT (186, 1.7%), ST (545, 4.9%), ST+LS (11, 0.1%) and LS (210, 1.9%). Compared to cases of unknown disease, QF cases had larger percentages of high‐risk occupations (16.2 versus 9.6%) but similar histories of animal contact (29.8 versus 25.1%). QF is an endemic disease in southern Taiwan. It is difficult to differentiate QF from ST, MT or LS only by high‐risk occupations and history of animal contact, and co‐infection of QF with these diseases should be considered.     

Ultrasonographic evaluation of renal dimension and resistive index in clinically healthy Korean domestic short-hair cats

Renal length, height, width, resistive index (RI), size of cortex, and medulla were determined by renal ultrasonography in 50 healthy Korean domestic short-hair cats. In the sagittal plane, the renal length was 3.83 ± 0.51 cm (mean ± SD) in the left kidney and 3.96 ± 0.48 cm in the right kidney, whereas the renal height was 2.42 ± 0.27 cm in the left kidney and 2.36 ± 0.28 cm in the right kidney. In the transverse plane, the renal height was 2.42 ± 0.28 cm in the left kidney and 2.38 ± 0.27 cm in the right kidney, whereas the renal width was: 2.65 ± 0.35 cm in the left kidney and 2.63 ± 0.31 cm in the right kidney. In the dorsal plane, the renal length was 3.84 ± 0.53 cm in the left kidney and 3.97 ± 0.54 cm in the right kidney, whereas the renal width was 2.65 ± 0.34 cm in the left kidney and 2.66 ± 0.33 cm in the right kidney. There were no significant differences (p > 0.05) among the same structure sizes measured in different planes. In the sagittal plane, the size of the renal cortex was 0.47 ± 0.08 cm in the left kidney and 0.47 ± 0.08 cm in the right kidney, whereas of the size of the renal medulla was 0.55 ± 0.30 cm in the left kidney and 0.50 ± 0.07 cm in the right kidney. RI evaluated by pulsed wave Doppler sonography was 0.52 ± 0.05 in the left kidney and 0.55 ± 0.05 in the right kidney. The actual renal dimensions determined by gross examination were not statistically different from those determined by ultrasonography. Furthermore the renal dimensions and RI were statistically correlated to the body weight of cats.     

The optimal size and placement of transdermal electrodes are critical for the efficacy of a transcutaneous pacemaker in dogs

Transcutaneous cardiac pacing (TCP) can be used in dogs with a high risk for bradyarrhythmias prior to anesthesia, either in an emergency room or intensive care unit setting. Furthermore, TCP can also be used on patients diagnosed with bradyarrhythmias that require temporary pacing at the induction of anesthesia for the implantation of a permanent pacemaker. Despite the importance of TCP in emergency medicine, no studies have evaluated the optimal size and placement of the transdermal electrodes crucial for the efficacy of TCP in dogs.This study evaluated four different sizes of electrodes (10.5, 20, 30 and 40 cm²), and four different anatomical sites (anterior–posterior, left–right, apex–base, modified left–right) in order to optimize the efficacy of TCP in dogs. Electrodes with a surface area of 20 cm² and a modified left–right placement minimized the pacing current and involuntary skeletal muscular contraction (muscular twitching) and so achieved the most optimal effect of TCP in dogs.