Effects of Apple Polyphenols and Taurine on Growth Performance, Tissue Morphology, and Lipid and Glucose Metabolism in Rice Field Eel (Monopterus albus) Fed High Oxidized Fish Oil.

The aim of this trial was to investigate the effects of apple polyphenols (AP) and taurine (TA) on the growth performance, tissue morphology, and lipid and glucose metabolism in rice field eel fed diets with high oxidized fish oil (OFO). A 10-week feeding experiment was conducted using juveniles (initial body weight 16.66 ± 0.02 g) fed five different diets. Three diets were formulated with various levels of OFO at 9.5, 600, and 800 meq·kg-1 and named as Control, POV600, and POV800 diet, respectively. The other two diets were POV600 and POV800 supplemented with 0.5% AP and 0.2% TA, respectively. Compared to the Control group, only the eels fed POV800 exhibited an increase in weight gain and specific growth rate along with a reduction in feed conversion ratio. AP and TA did not affect growth performance; juveniles fed AP, however, showed a decrease in liver weight. Both POV600 and POV800 decreased nuclei number and increased vacuoles size in the liver. POV800 damaged the intestinal structure integrity and reduced goblet cells number. AP repaired the liver damage on nuclei number and vacuoles size in fish fed with POV600 diet, while TA mitigated intestinal histopathological damage on intact structure and goblet cells number. The mRNA expression level of liver ampkα in fish fed AP was upregulated, while dietary TA upregulated the mRNA expression levels of liver ampkα and accα. In the muscle, POV600 downregulated mRNA expression levels of accα, cpt1, and lipin, whereas POV800 upregulated mRNA expression levels of accα, pparα, and lipin. Dietary AP and TA could counteract the effects of POV600 and POV800 diet on muscle lipid metabolism. Both POV600 and POV800 diets upregulated mRNA expression levels of liver pck1 and gsk3α. AP and TA both downregulated mRNA expression level of liver pck1, while only TA downregulated the expression of liver gsk3α. AP increased the mRNA expression level of gsk3α in muscle. In summary, inclusion of AP and TA did not affect growth performance but showed a potential to alleviate liver or intestinal damages induced by a high OFO diet. Dietary AP and TA were also found to regulate mRNA expression of genes related to lipid and glucose metabolism.

Association of selenium profile with neutralizing antibody response to inactivated SARS-CoV-2 vaccination.

BACKGROUND: Selenium profile has been related with humoral immune response after vaccination, but evidence with regard to inactivated SARS-CoV-2 vaccine is lacking. OBJECTIVE: The current study aimed to examine the relationship between selenium profile and neutralizing antibody response to inactivated SARS-CoV-2 vaccine. METHODS: Plasma selenium and selenoprotein P concentrations, neutralizing antibody against the wild-type and Omicron variant were measured at baseline and at 14 days, 98 days after the third dose of inactivated SARS-CoV-2 vaccine. RESULTS: Neutralizing antibody against the wild-type and Omicron variant increased significantly after the third vaccination dose. Both higher plasma selenium and selenoprotein P were associated with increased neutralizing antibody against the wild-type strain at baseline. Moreover, higher plasma selenoprotein P was associated with increased neutralizing antibody against Omicron variant at baseline. However, nonsignificant association were observed after the third vaccine dose. CONCLUSION: Higher selenium profile was associated with neutralizing antibody response before the third dose of inactivated SARS-CoV-2 vaccine, but not after the third dose. Further prospective cohort studies are warranted to confirm our findings.

Oryza sativa PECTIN DEFECTIVE TAPETUM1 affects anther development through a pectin-mediated signaling pathway in rice.

Galacturonosyltransferase (GalAT) is required for the synthesis of pectin, an important component of plant cell walls that is also involved in signal transduction. Here, we describe the rice (Oryza sativa) male-sterile mutant O. sativa pectin-defective tapetum1 (ospdt1), in which GalAT is mutated. The ospdt1 mutant exhibited premature programmed cell death (PCD) of the tapetum and disordered pollen walls, resulting in aborted pollen grains. Pectin distribution in the anther sac was comparable between the mutant and the wild-type, suggesting that the structural pectin was not dramatically affected in ospdt1. Wall-associated kinases are necessary for the signal transduction of pectin, and the intracellular distribution of O. sativa indica WALL-ASSOCIATED KINASE1 (OsiWAK1), which binds pectic polysaccharides to its extracellular domain, was affected in ospdt1. OsiWAK1 RNA interference lines exhibited earlier tapetal PCD, similar to ospdt1. Furthermore, overexpression of OsiWAK1 in ospdt1 lines partially rescued the defects observed in ospdt1, suggesting that OsiWAK1 plays pivotal roles in the function of OsPDT1. These results suggest that the mutation of OsPDT1 does not dramatically affect structural pectin but affects components of the pectin-mediated signaling pathway, such as OsiWAK1, and causes male sterility.

OsFLA1 encodes a fasciclin-like arabinogalactan protein and affects pollen exine development in rice.

KEY MESSAGE: OsFLA1 positively regulates pollen exine development, and locates in the cellular membrane. Arabinogalactan proteins are a type of hydroxyproline-rich glycoprotein that are present in all plant tissues and cells and play important roles in plant growth and development. Little information is available on the participation of fasciclin-like arabinogalactan proteins in sexual reproduction in rice. In this study, a rice male-sterile mutant, osfla1, was isolated from an ethylmethanesulfonate-induced mutant library. The osfla1 mutant produced withered, shrunken, and abortive pollen. The gene OsFLA1 encoded a FLA protein and was expressed strongly in the anthers in rice. Subcellular localization showed that OsFLA1 was located in the cellular membrane. In the osfla1 mutant, abnormal Ubisch bodies and a discontinuous nexine layer of the microspore wall were observed, which resulted in pollen abortion and ultimately in male sterility. The results show the important role that OsFLA1 plays in male reproductive development in rice.

High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses.

Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection.IMPORTANCE Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.

Ginsenoside Rg1 modulation on thrombospondin-1 and vascular endothelial growth factor expression in early renal fibrogenesis in unilateral obstruction.

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.

Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction.

OBJECTIVE: To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO). METHODS: In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis. RESULTS: In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05). CONCLUSION: Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-beta in rats with unilateral ureteral obstruction.

Astragalus mongholicus (AM) derived from the dry root of Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction (UUO). We divided 48 Sprague-Dawley rats randomly into 4 groups: sham-operated group (Sham), untreated UUO group, AM-treated (10 g/(kg x d)) UUO group, and losartan-treated (20 mg/(kg x d)) UUO group as positive control. Haematoxylin & eosin (HE) and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin (FN), type I collagen (colI), hepatocyte growth factor (HGF), transforming growth factor-beta1 (TGF-beta1), and alpha-smooth muscle actin (alpha-SMA) were analyzed by real-time polymerase chain reaction (PCR), immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and colI from UUO by reducing the expressions of TGF-beta1 and alpha-SMA (P<0.05), whereas HGF increased greatly with AM treatment (P<0.05). Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition of myofibroblast activation, inducing of HGF and reducing of TGF-beta1 expression.

[Effect of Astragalus mongholicus on expression of transforming growth factor- beta1 in SD rats with unilateral ureteral occlusion].

OBJECTIVE: To study the effect of Astragalus mongholicus (AM) on the expression of transforming growth factor-beta1 (TGF-beta1) in SD rats with unilateral ureteral occlusion (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM. METHOD: Fifty-four Sprague-Dawley rats were randomly divided into 4 groups: sham-operation group, the UUO group and AM treatment group. After administration of AM (10 g kg(-1) d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of TGF-beta1 and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry staining sections. The mRNA of TGF-beta1 and alpha-SMA were reverse transcribed and quantified by real-time PCR. The expression of TGF-beta1 protein were assessed by Western blot. RESULT: Renal damage was exacerbated and the expression of alpha-SMA and TGF-beta1 were all significantly increased in UUO group compared with those of sham-operation group (P<0.05) at each time point. Tubular impairment and interstitial fibrosis were alleviated, and up-regulations of expressions of TGF-beta1 and alpha-SMA were significantly suppressed by AM treatment (P<0.05). CONCLUSION: AM can ameliorate renal interstitial fibrosis induced by UUO in vivo. The mechanisms of its antifibrotic effects might be related with the down-regulation of TGF-beta1 expression and suppression of tubular epithelial myofibroblast transdifferentiation in the progress of renal interstitial fibrosis.

[Effect of Astragalus mongholicus on expression of hepatocyte growth factor in SD rats with unilateral ureteral obstruction].

OBJECTIVE: To study the effect of Astragalus mongholicus (AM) on the expression of hepatocyte growth factor (HGF) in SD rats with unilateral ureteral obstruction (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM. METHODS: Fifty four Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (SOR), UUO group (UUO) and UUO + AM group (AM). After administration of AM[10 g/ (kg x d)] for 3, 7 and 14 days,the histological changes of renal interstitial tissues were observed dynamically, and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The protein expression of HGF and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry. The mRNA expression of HGF and alpha-SMA were determined by real-time PCR. The expression of HGF and its receptor (C-met) were assessed by Western blot. RESULTS: Renal damage was exacerbated and the expression of alpha-SMA was significantly increased in UUO group compared with those of SOR group (P < 0.05) at each time point. HGF and C-met expression peaked at the 7th day after UUO and then decreased greatly. After AM intervention, tubular impairment and interstitial fibrosis were alleviated, up-regulations of alpha-SMA expressions was significantly suppressed, whileas the expression of HGF and C-met were significantly increased when compared with UUO group (P < 0. 05) at each time point. CONCLUSION: AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of its antifibrotic effects may be related with the up-regulation of HGF and C-met expression, and the suppression of tubulo-epithelial mesenchymal transdifferentiation in renal intersitial progress.

[Regulative effect of Astragalus mongholicus on hepatocyte growth factor and transforming growth factor-beta1 in rats with unilateral ureteral obstruction].

OBJECTIVE: To study the effect of Astragalus mongholicus (AM) on renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats in order to elucidate the mechanisms underlying the renoprotective effects of AM. METHODS: 54 Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (Sham), the UUO group(UUO) and UUO + AM group (AM). The rats were treated at the doses of 10 g/(kg X d) AM for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expressions of transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) were measured by immunohistochemistry staining sections. The mRNA of HGF and TGF-beta1 were reverse transcribed and quantified by real-time PCR. The expressions of HGF and TGF-beta1 protein were assessed by Western blot. RESULTS: Renal damages were exacerbated and the expressions of TGF-beta1 were significantly increased in UUO group in comparison with those of Sham group (P < 0.05) at each time point. HGF expression increased initially and peaked at the day of 7 after UUO and then decreased greatly. The tubular impairment and interstitial fibrosis were alleviated, up-regulations of expressions of TGF-beta1 were significantly suppressed, while expressions of HGF were significantly increased in UUO + AM group in comparison with UUO group (P < 0.05). CONCLUSION: AM could ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of antifibrotic effects of AM may be associated with up-regulation of HGF expression and down-regulation of TGF-beta1 expression in renal intersitial progress.

[Effect of Astragalus mongholicus on expression of connective tissue growth factor in kidney of SD rats with unilateral ureteral obstruction].

OBJECTIVE: To study the effect of Astrangalus mongholicus (AM) on the expression of Connective Tissue Growth Factor (CTGF) in SD rats with Unilateral Ureteral Obstruction (UUO) and elucidate the mechanism underlying the renorotective effects of AM. METHODS: 36 Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (Sham), UUO group (UUO) and UUO + AM group (AM). After administration of AM (10 g/kg x d) for 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expressions of CTGF and alpha-smooth muscle actin (alpha-SMA) were measured by immunohistochemistry staining sections. The mRNA of CTGF and alpha-SMA were reversely transcribed and quantified to real-time PCR. The expression of CTGF protein was assessed by Western blot. RESULTS: Renal damage was exacerbated and the expressions of alpha-SMA and CTGF significantly increased in UUO group compared with those of Sham group (P < 0.05) at each time point. Tubular impairment and interstitial fibrosis were alleviated, and up-regulations of expressions of CTGF and alpha-SMA were significantly depressed by AM treatment (P < 0.05). CONCLUSIONS: AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanism of its antifibrotic effects may be related to the down-regulation of CTGF expression, following suppression of tubulo-epithelial mesenchymal transdifferentation in renal intersitial progress.