Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection.

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.

Abnormality of intestinal cholesterol absorption in ApcMin/+ mice with colon cancer cachexia.

Colorectal cancer syndrome has been one of the greatest concerns in the world, particularly in developed countries. Several epidemiological studies have shown that dyslipidemia may be associated with the progression of intestinal cachexia, but there is little research on the function of the small intestine, which is involved in blood lipid metabolism, in dyslipidemia. In the present study, we aimed to explore the function of intestinal cholesterol absorption in the ApcMin/+ mouse model using an intestinal lipid absorption test. We found that both triglyceride (TG) and total cholesterol (TC) uptake were inhibited in the intestine of ApcMin/+ mice with age and the intestinal peroxisome proliferator-activated receptor α (PPARα) downregulated the processes of ß-oxidation, oxidative stress response, and cholesterol absorption in APC-deficient mice. In addition, reduced expression levels of farnesoid X receptor (FXR) and apical sodium-dependent bile acid transporter (ASBT) indicated that bile acid metabolism might be associated with intestinal cholesterol absorption in ApcMin/+ mice. Thus, our data suggested that the intestine plays an essential role in cholesterol uptake and that bile acid metabolism seems to cause a decrease in intestinal cholesterol uptake in ApcMin/+ mice.

[Effect of Chuanhuang No. 1 recipe on renal function and micro-inflammation in phase 3 chronic kidney disease patients].

OBJECTIVE: To observe the effect of Chuanhuang No.1 Recipe (CHR) on renal function and micro-inflammation in phase 3 chronic kidney disease (CKD) patients. METHODS: Totally 60 phase 3 CKD patients were randomly assigned to the treatment group (treated by CHR) and the control group (treated by Losartan Potassium), 30 in each group. All patients received basic treatment. Patients in the treatment group took CHR decoction, 400 mL each time, one dose per day, while those in the control group took Losartan Potassium, 50-100 mg per day. All medication lasted for 24 weeks. Changes of serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), serum uric acid (UA), 24 h urinary protein excretion (24 h U-pro), urinary microalbumin (U-Alb), high-sensitivity C-reactive protein (hs-CRP), serum tumor necrosis factor (TNF)-alpha, and serum IL-6 were detected and compared before and after treatment. Efficacy was also compared. RESULTS: Compared with before treatment, SCr and BUN significantly decreased in the treatment group (P<0.05, P<0.01); eGFR in- creased (P<0.05). Only UA obviously decreased in the control group (P<0.05), but with no obvious change in SCr, BUN, or eGFR. Compared with before treatment, 24 h U-pro decreased after treatment in the treatment group (P<0.05), but with less decreased level when compared with the control group. U- Alb was also significantly decreased in the control group (P<0.01). There was statistical difference in 24 h U-pro and U-Alb between the two groups after treatment (P<0.05). Compared with before treatment, hs-CRP obviously decreased after treatment in the two groups, but serum levels of TNF-alpha and IL-6 obviously decreased only in the treatment group (P<0.05). The total effective rate was obviously higher in the treatment group than in the control group (70.00% vs. 43.33%, P<0.01). CONCLUSION: CHR could efficiently improve the renal function of phase 3 CKD patients and alleviate the micro-inflammation.

[Short-term effects of chemotherapy combined with hydroxycamptothecine and oxaliplatin in treatment of recurrent and metastatic colorectal cancer].

BACKGROUND & OBJECTIVE: Although 5-fluarouracil (5-FU)-based chemotherapy has become a standard regimen for treatment of recurrent and metastatic colorectal cancer, the efficacy, as a second line therapy, is not high. Thus, it is necessary to find a new regimen as a substitute. This study was to evaluate the short-term effects and toxicity of combination of hydroxycamptothecine (HCPT) plus oxaliplatin (L-OHP) protocol in the treatment of recurrent and metastatic colorectal cancer. METHODS: 47 patients with pathological evidence of recurrent and metastatic colorectal cancer were enrolled and treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with (L-OHP 130 mg/m(2), day 1 and HCPT 6 mg/m(2), day 1-4) and the chemotherapy was repeated every 3 weeks. The short-term effects and side effects were evaluated after every 2 cycles for each patient. RESULTS: 38 cases were evaluable and RR [complete remission (CR)+partial remission (PR)] was 36.8% (14/38). KPS was improved in 20 cases (52.6%). In total 86 cycles, leucopenia occurred in 59 cycles (68.6%), 18 cycles (30.5%) in grade III and IV, and diarrhea occurred in 48 cycles (55.8%), 18 cycles (37.5%) in grade III and IV. One year survival rate was 40.0% and medium overall survival (mOS) and medium progression free survival (mPFS) were 11.7 and 7.8 months, respectively. CONCLUSIONS: HCPT plus L-OHP regimen achieved relatively satisfactory short-term effects in the treatment for colorectal cancer patients, who suffered from recurrence and metastasis after the first-line chemotherapy with 5-FU. The main toxicities of the regimen were leucopenia and diarrhea.

[Short-term effects of chemotherapy with combination of hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers].

OBJECTIVE: To evaluate the short-term therapeutic effects and side effects of combined hydroxycamptothecine and oxaliplatin in the treatment of advanced digestive tract cancers. METHODS: Thirty patients suffering from advanced digestive tract tumors including gastric cancer 8, colorectal cancer 20, cholecystic cancer 1 and malignant fibroadenoma 1 were studied. They were treated with hydroxycamptothecine plus oxaliplatin for 2 cycles with interval of 21 days. RESULTS: The complete response, partial response, stable disease and progressive disease rates were 3.3% (1/30), 36.7% (11/30), 53.3% (15/30) and 6.7% (3/30) respectively with an overall response rate (CR + PR) of 40.0% (12/30). In the whole 77 cycles, leukocytopenia was observed in 34 cycles (44.2%) and 19 cycles (55.9%) at grades III and IV. Diarrhea developed in 42 cycles (54.5%) and 20 cycles (47.6%) grades III and IV. The other side effects were fever, alopecia, nausea and vomiting, constipation, hepatic and renal function abnormity and neuritis. CONCLUSION: Satisfactory response rate is obtainable in advanced colorectal cancer as treated by hydroxycamptothecine plus oxaliplatin. The toxicity consists of severe leukocytopenia and diarrhea.