Characteristic of the components and the metabolism mechanism of goat colostrum: a review.

Colostrum contains large number of nutrients that promote the growth, differentiation, and biological functions for goat kids early somatic cells, which is crucial to meet the nutritional demands, immune function, and the health of goat kids later growth. Great attention has been given not only to nutritional ingredient differences between colostrum and normal milk, but also to function differences, and their effect on the physical and sensory properties of goat kid's growth performance and health status. This paper reviews the research progress of goat colostrum in recent years, mainly including the colostrum yield, components, i.e., proteins, lactose, and immunoglobulin, as well as the influence factor, i.e., number of lactation and littler size, nutrition during the gestation, and breeding environment. In addition, this review aims to summarize the synthesis and secretion mechanisms, and the digestion and absorption mechanism of goat colostrum. We conclude that even though the composition and physicochemical properties of goat colostrum are highly dynamic and variable, and the digestion and absorption mechanism has not been made fully clear until now, direct feed microbial (DFM) may be a promising alternative for improving the quality of colostrum that should be further explored for their practical usage.

Changes in colostrum ingredients of Hu sheep, as well as the missense mutation genes associated with colostrum yield.

This study focused on the changes in the composition and immune evolution in milk from birth to 144 h postpartum and the genes associated with the colostrum yield of Hu sheep. Twelve Hu sheep, which were bred carefully under animal health standards and have a litter size of two kids and similar gestation length (149 ± 1 days), were used. Lambs were transferred into their own cots to avoid interference. The compositional content (i.e., fat, protein, and lactose) and some other properties, including daily colostrum yield, DM, and SNF, were determined. In addition, immunity molecules (IgG, IgA, and IgM concentrations) received remarkable attention. The DM, SNF, fat, and protein contents were higher in the first days postpartum and then dropped quickly from the time of birth to 144 h postpartum. However, the lactose content displayed an increasing pattern and reached normal milk percentage at 48 h. The highest IgG (103.17 mg/mL), IgA (352.82 µg/mL), and IgM (2.79 mg/mL) colostrum concentrations were observed at partum, decreased quickly, and finally stabilized. The change law of concentration of IgA and IgM in colostrum are the same with IgG. Furthermore, the whole-genome resequencing was performed, and a missense variant locus in the SRC gene and two missense locus variants in the HIF1A gene were significantly associated with the colostrum yield of sheep by using the whole-genome selection signal detection analysis. In conclusions, colostrum contains abundant nutrients especially immunoglobulin, and the HIF1A gene may be used as candidate genes for colostrum yield, which has important information as a basic knowledge for the Hu sheep breeding program.

Effects of lactation number and litter size on the chemical composition and immune components of goat colostrum.

This study aimed to evaluate the effect of the number of lactations and litter size on the chemical composition, immunoglobulins, and cytokines of goat colostrum. The experiment was conducted at the Animal Research Base, Mianyang Academy of Agricultural Sciences, from February to March 2021. After delivery, 48 colostrum samples were obtained every 24 h by manual milking from both udders. The contents of colostrum proteins, IgA, and IgM increased markedly up to 48 h postpartum, reaching 250 and 1250 µg/mL, respectively (p < 0.01 compared with 0 h). However, the total Ig and IgG contents dropped quickly at 48 h postpartum to around 4.5 and 6 mg/mL, respectively, and continued to do so until 96 h postpartum (p < 0.01). As for litter size, the colostrum DM, fat, total Ig, IgG, INF-γ, and IL-2 of twin-birth goats were higher than those of single-birth goats at 0 h postpartum. Moreover, the colostrum of multiparous goats contained higher total Ig, IgA, IgG, and INF-γ concentrations than that of primiparous goats at 0 h postpartum (p < 0.01). However, the colostrum INF-α and IL-5 contents of multiparous goats were lower than those of primiparous goats at 0 h postpartum (p < 0.05). Available information indicates that colostrum secretion takes place until 48 h postpartum and that the effect of litter size and lactation number on colostrum quality is observed at 0 h postpartum.

RNA-Binding Protein MAC5A Is Required for Gibberellin-Regulated Stamen Development.

The development of floral organs is coordinated by an elaborate network of homeotic genes, and gibberellin (GA) signaling is involved in floral organ development; however, the underlying molecular mechanisms remain elusive. In the present study, we found that MOS4-ASSOCIATED COMPLEX 5A (MAC5A), which is a protein containing an RNA-binding motif, was involved in the development of sepals, petals, and stamens; either the loss or gain of MAC5A function resulted in stamen malformation and a reduced seed set. The exogenous application of GA considerably exacerbated the defects in mac5a null mutants, including fewer stamens and male sterility. MAC5A was predominantly expressed in pollen grains and stamens, and overexpression of MAC5A affected the expression of homeotic genes such as APETALA1 (AP1), AP2, and AGAMOUS (AG). MAC5A may interact with RABBIT EARS (RBE), a repressor of AG expression in Arabidopsis flowers. The petal defect in rbe null mutants was at least partly rescued in mac5a rbe double mutants. These findings suggest that MAC5A is a novel factor that is required for the normal development of stamens and depends on the GA signaling pathway.

Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: A systematic review and meta-analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China's experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19. METHODS: Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis. RESULTS: Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis. CONCLUSION: Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.

Ultrasonicated sour Jujube seed flavonoids extract exerts ameliorative antioxidant capacity and reduces Aß-induced toxicity in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Sour Jujube seed from Ziziphus jujuba Mill. var. Spinosa (Bunge) Hu ex H. F. Chow is a traditional Chinese herb. It was demonstrated with significant activities in anti-depression and antioxidant by numerous pharmacological studies. Flavonoids is one of the main constituents in sour Jujube seed. AIM OF THE STUDY: The aim of this study was to propose a green ultrasound-assisted extraction (UAE) process of flavonoids from sour Jujube seed. MATERIALS AND METHODS: The extraction parameters were investigated and optimized using single factor experiments, Plackett-Burman design (PBD) and response surface methodology (RSM). Moreover, a comparative analysis between ultrasound-assisted extraction and heat reflux extraction was performed to verify the ameliorating effects of ultrasound-assisted extraction on the flavonoids yield, the composition, antioxidant capacities in vitro and ROS scavenging capacity in PC12 cells. Meanwhile, the effects of flavonoids extract (FE) on Aß transgenic Caenorhabditis elegans (GMC101) behavior were investigated. RESULTS: The optimal extracting conditions of total flavonoids were as follows: ethanol concentration 70.60 (v/v%), liquid-solid ratio 15.02:1 mL/g, ultrasonic power 404 W, extraction time 60.03 min. The highest extraction yield was 1.59%. When compared to Heat reflux extraction (HRE) that only has gained a yield of 1.356%. Approximately, the UAE method was able to increase the yield by 17.11%. Moreover, FE extracted by UAE displayed larger capacity of scavenging ABTS, DPPH, superoxide, and hydroxyl radicals and reducing the level of ROS accumulation in PC12 cells, suggesting the biological functions of these compounds could be also better protected under UAE conditions. Furthermore, FE could also increase the chemotaxis and heat stress resistance ability, delay the paralysis and extend the lifespan of Caenorhabditis elegans. CONCLUSION: UAE is a green and efficient technique for the preparation of flavonoids from sour Jujube seed. The flavonoids extract can reduce Aß-induced toxicity in Caenorhabditis elegans.

A glucogalactomannan isolated from Agaricus bisporus induces apoptosis in macrophages through the JNK/Bim/caspase 3 pathway.

Agaricus bisporus is one of the most important edible and medicinal mushrooms in the world. It has been well known that Agaricus bisporus has an immunoregulatory role, but its active ingredients have not been completely identified. In this study, a glucogalactomannan named TJ3 was isolated and purified from Agaricus bisporus. TJ3 (827 kDa) is composed of mannose, galactose, glucose and xylose in the ratio 28.26 : 27.82 : 20.88 : 9.87 mainly joined by ß-linkages. Functional analysis of TJ3 revealed that it effectively induced apoptosis in RAW 264.7 cells, a mouse macrophage cell line. Cell apoptosis was determined by an Annexin V/PI staining assay. After treatment with TJ3 (2 µg mL-1) for 16 h, apoptosis was observed in 34% of the Raw cells (9% in the non-treated control cells). TJ3 treatment remarkably increased the production of cleaved caspase-3, PARP and Bim, and decreased the level of Bcl-2 although no obvious change in the level of Bax was observed. Interestingly, further elucidation of the molecular mechanism underlying the role of TJ3 in the induction of apoptosis showed that TJ3 activated the JNK signaling pathway through TLR4 and subsequently promoted the expression of Bim and activation of caspase-3. Our results demonstrate that TJ3 may be a novel active component in Agaricus bisporus responsible for its immunoregulatory role by the induction of macrophage apoptosis.

Weikangning therapy in functional dyspepsia and the protective role of Nrf2.

Functional dyspepsia (FD) is a non-organic gastrointestinal disorder that has a marked negative impact on quality of life. Compared with conventional pharmacological therapies, the traditional Chinese medicine weikangning (WKN) is a safe and effective treatment for FD. The present study aimed to determine the molecular mechanisms underlying the efficacy of WKN. The effect of different concentrations of WKN on the proliferation of the human gastric mucosal epithelial cell line GES-1 was assessed. The optimal WKN concentration to promote cell proliferation was determined, and this concentration was used to examine the effect of WKN compared with a domperidone-treated positive control group on the antioxidant capacity of GES-1 cells. The effect of WKN treatment on the growth and antioxidant activity of GES-1 cells was also assessed following nuclear factor erythroid 2 like 2 (Nrf2) knockdown. The optimal WKN dose for promoting cell growth was determined to be 0.025 mg/ml; at this concentration the expression of the antioxidant proteins glutathione S-transferase P and superoxide dismutase 2 (SOD2) were significantly elevated (P<0.0001). Furthermore, the amount of reduced glutathione and activity of SOD2 were significantly increased (P<0.0001 and P<0.01, respectively), and malondialdehyde content was significantly decreased, compared with the controls (P<0.001). With WKN treatment, the transcription of Nrf2 and its downstream genes were significantly upregulated (P<0.01), and the level and nuclear distribution of Nrf2 protein was also markedly increased. Following Nrf2 silencing, the protective antioxidant effects of WKN treatment were impaired and GES-1 cell proliferation decreased. The results of the present study suggest that the efficacy of WKN in protecting gastric mucosal epithelial cells in FD is antioxidant-dependent and mediated by Nrf2 activation.

Gastrointestinal Absorption and Metabolic Dynamics of Jujuboside A, A Saponin Derived from the Seed of Ziziphus jujuba.

Jujuboside A (JuA), an active saponin, is responsible for the anxiolytic and sedative effects of Zizyphi Spinosae Semen (ZSS). In this study, the gastrointestinal absorption and metabolic dynamics of JuA were investigated in vivo and in vitro. The results showed that the bioavailability was 1.32% in rats, indicating only a trace amount of JuA was able to be absorbed. Further investigation revealed that its poor bioavailability was not caused by malabsorption but by the metabolic process. JuA was hydrolyzed largely in the stomach before being absorbed into the different parts of the intestine (especially duodenum and colon), and the gastric environment played a vital role in this process. Furthermore, the metabolites, jujuboside B (JuB) and jujubogenin, exhibited significant effects on the expression and activation of γ-amino-butyric acid A (GABA(A)) receptors. Our findings demonstrate that the metabolites of the saponin, not the original molecule, should be responsible for the specific bioactivities.

Degradation Kinetics of 6‴-p-Coumaroylspinosin and Identification of Its Metabolites by Rat Intestinal Flora.

6‴-p-Coumaroylspinosin (P-CS), a bioactive flavonoid, is typically extracted from Semen Ziziphi Spinosae (SZS). In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine P-CS for investigating the degradation characteristics of P-CS incubated with rat feces. The results showed that P-CS degraded rapidly and the degradation speeds varied depending upon the P-CS concentrations (3, 15, and 30 µg/mL). The degradation of P-CS processes follow first-order kinetics. On the basis of the mass spectrometry (MS) spectrum mode of the product ions, two main metabolites of P-CS were identified. Swertisin was the main metabolite at 3 and 15 µg/mL, while spinosin was produced when the P-CS concentration was 30 µg/mL. Spinosin and swertisin could improve mRNA transcription levels of glutamate receptor K1, K2, and K3 (GluK1, GluK2, and GluK3) subunits in rat hippocampal neurons. In addition, they showed an obvious synergistic effect in this respect. Collectively, the results can be used to explain the metabolic and pharmacological mechanisms of P-CS.

[Transcutaneous Electrical Stimulation Undergoing Emergency Treatment of Zusanli (ST 36) Is Beneficial to Rescued Organophosphorus Pesticide Poisoning Patients].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) of Zusanli (ST 36) on gastrointestinal activities in organophosphorus pesticide poisoning (OPP) patients undergoing emergency treatment so as to explore its action in scavenging gastrointestinal toxicant. METHODS: A total of 116 OPP patients were randomly divided into control group and TAES group (n=58 in each group) according to the simple random sampling method. All the patients received comprehensive treatment including gastric lavage, catharsis, oral administration of atropine Pralidoxime Chloride, Omeprazole, etc. For patients of the TAES group, TAES stimulation (30 Hz/60 Hz, 15-20 mA) was applied to bilateral Zusanli (ST 36) for 30 min, 3 times a day till black stool was discharged. The vomiting times after catharsis, the time of the first defecation and black stool discharge, the dosage of atropine and the length of patient stay in hospital were recorded. RESULTS: Of the two 58 cases of OPP patients in the control and TAES groups, 11 (18.9%) and 3 (5.2%) underwent vomiting after catharsis, being significantly lower in the TAES group (P<0.05). Compared with the control group, the time of first defecation and black stool discharge, the dosage of the administrated atropine and the time of hospitalization were significantly lower in the TAES group (P<0.05). CONCLUSION: TAES of ST 36 may lower incidence of emesis, enhance the cathartic effect, promote gastrointestinal poison discharge, reduce total atropine dosage and shorten the hospitalization time in OPP patients, favoring the patient's rehabilitation.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

OBJECTIVE: To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. METHOD: Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. RESULT: According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. CONCLUSION: Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

Development, validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing.

It has been demonstrated that two-dimensional (2D) monolayer cancer cell proliferation assay for anti-cancer drug screening is a very artificial model and cannot represent the characteristics of three-dimensional (3D) solid tumors. The multi-cellular in vitro 3D tumor spheroid model is of intermediate complexity, and can provide a bridge to the gap between the complex in vivo tumors and simple in vitro monolayer cell cultures. In this study, a simple and cost-effective cancer 3D spheroid assay suitable for small molecule anti-cancer compound screening was developed, standardized and validated on H292 non-small lung cancer cell line. A pilot screening with this assay was performed utilizing a compound library consisting of 41 anti-cancer agents. The traditional 2D monolayer cell proliferation assay was also performed with the same cell line and compounds. A correlational study based on the IC(50) values from the 2D and 3D assays was conducted. There is low correlation with the two sets of biological data, suggesting the two screening methods provide different information regarding the potency of the tested drug candidates.

Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via HIF-1α/VEGFA.

BACKGROUND: The mechanism of rapid growth of the residual tumor after radiofrequency (RF) ablation is poorly understood. In this study, we investigated the effect of hyperthermia on HepG2 cells and generated a subline with enhanced viability and dys-regulated angiogenesis in vivo, which was used as a model to further determine the molecular mechanism of the rapid growth of residual HCC after RF ablation. METHODOLOGY/PRINCIPAL FINDINGS: Heat treatment was used to establish sublines of HepG2 cells. A subline (HepG2 k) with a relatively higher viability and significant heat tolerance was selected. The cellular protein levels of VEGFA, HIF-1α and p-Akt, VEGFA mRNA and secreted VEGFA were measured, and all of these were up-regulated in this subline compared to parental HepG2 cells. HIF-1α inhibitor YC-1 and VEGFA siRNA inhibited the high viability of the subline. The conditioned media from the subline exerted stronger pro-angiogenic effects. Bevacizumab, VEGFA siRNA and YC-1 inhibited proangiogenic effects of the conditioned media of HepG2 k cells and abolished the difference between parental HepG2 cells and HepG2 k cells. For in vivo studies, a nude mouse model was used, and the efficacy of bavacizumab was determined. HepG2 k tumor had stronger pro-angiogenic effects than parental HepG2 tumor. Bevacizumab could inhibit the tumor growth and angiogenesis, and also eliminate the difference in tumor growth and angiogenesis between parental HepG2 tumor and HepG2 k tumor in vivo. CONCLUSIONS/SIGNIFICANCE: The angiogenesis induced by HIF1α/VEGFA produced by altered cells after hyperthermia treatment may play an important role in the rapid growth of residual HCC after RF ablation. Bevacizumab may be a good candidate drug for preventing and treating the process.

[A new method for quick identification for fufang danshen tablets by AOTF-near infrared spectroscopy].

OBJECTIVE: To establish a new method using AOTF-Near infrared spectroscopy for fast identifying Fufang Danshen tablets. METHOD: Near-infrared spectroscopy of Fufang Danshen tablets from different factories and different bacth numbers were collected and the discriminant analysis model (FFDS-C) was established with principal component analysis. This model was applied to predict the the different samples of Fufang Danshn tablets. RESULT: The model can be used to precisely identify Fufang Danshen tablets from other samples. CONCLUSION: The method with low consumption is simple and quick and can be applied to the identification of the Fufang Danshen tablets.

Phosphorus fractionation and bio-availability in Taihu Lake (China) sediments.

Typical sediments from Taihu Lake, a meso-to-hypereutrophic lake, were collected and examined on the basis of P-fractionation by sequential extraction scheme. Sedimentary inorganic phosphorus were fractioned into four forms and the rank order according to the mean concentration of P-fractions in Taihu Lake was NaOH-P > BD-P > HCI-P > NH4Cl-P. The concentrations of BD-P were linearly correlated with the content of active Fe (R2 = 0.96). Also, the linear relationship between the sum of BD-P and NaOH-P and the sum of active Fe and active Al content was observed within the six sediments investigated (R2 = 0.96). Moreover, the bio-available phosphorus (BAP) content was estimated by the sum of NH4 Cl-P, BD-P, and NaOH-P, viz. BAP = NH4 Cl-P + NaOH-P + BD-P. In Taihu Lake, the BAP contents are ranging from 0.10 mg/g dw to 1.25 mg/g dw, and average 0.40 mg/g dw for all sediment samples. The relative contributions of BAP to total sedimentary phosphorus (TP) and inorganic sedimentary phosphorus (IP) range from 18.67% to 50.79% (33.61% on average) and from 52.82% to 82.09% (67.81% on average), respectively.

Phosphorus adsorption on natural sediments: modeling and effects of pH and sediment composition.

The classic Langmuir isotherm equation was modified to describe phosphorus (P) adsorption on P-polluted sediments. The P adsorption characteristics of six sediment samples from Chinese Taihu Lake were studied by short-term isotherm batch experiments and related to sediment composition. The maximum P adsorption capacities (PAC) and P-binding energy constant (k) were obtained by nonlinearly fitting sorption data using the modified Langmuir isotherm model. Native adsorbed exchangeable phosphorus (NAP), the zero equilibrium P concentration value (EPC(0)), and partitioning coefficients (K(p)) were subsequently calculated by corresponding formulae. K(p) and PAC were linearly related to the contents of active Fe and Al in sediments by least squares regression analyses (R(2) approximately 0.9 for both). The effect of pH in a wide range on adsorption process was investigated and H2PO4- was presumed to be the preferential sorption species in overall sorption process. The fact that the amount of P sorbed and zeta potential of sediment particles have no necessary relationship reveals that a strong contribution to the P binding still comes from a ligand-exchange process on the Me-OH(2+) and Me-OH sites rather than electrostatic attraction. In addition, the influence of oxidation-reduction potential (ORP) was investigated and discussed and the dual nature of sediments as a pool or source of P in natural waters was evaluated in site T1-T4.

Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1.

Phospholipid scramblase 1 (PLSCR1) is an IFN-inducible, endofacial plasma membrane protein that has been proposed to mediate accelerated transbilayer movement of plasma membrane phospholipids in cells exposed to elevated cytoplasmic [Ca (2+)]. The marked transcriptional up-regulation of this gene by IFN in a wide variety of cell types suggested that PLSCR1 might also contribute to biological effects associated with IFN. To study the potential contribution of cellular PLSCR1 to the antiproliferative and tumor-suppressive activities of IFN, PLSCR1 cDNA was stably expressed in the human ovarian cancer cell line HEY1B, and the growth of these cells was compared with matched vector transfected controls both in vitro and in vivo. Whereas we detected no difference in either growth rate or morphology between PLSCR1-transfected cells and vector controls during in vitro culture in serum, when these cells were implanted s.c. into athymic nude mice, we observed a marked suppression of tumor development from cells transfected to express elevated levels of PLSCR1. Tumors from the PLSCR1-transfected cells were greatly reduced in size, showed increased infiltration of leukocytes and macrophages, and appeared to undergo differentiation to a more uniform and spindle-shaped morphology that markedly contrasted the highly undifferentiated and pleiomorphic cell shape normally observed for HEY1B cells in vitro or for vector-transfected control HEY1B cells both in vitro and in vivo. These data suggest that the up-regulation of PLSCR1 expression in tumor cells exposed to IFN may contribute to the observed tumor-suppressive action of this cytokine.