Blocking Factor Research Articles

Intestinal Immune Cell Populations, Barrier Function, and Microbiomes in Broilers Fed a Diet Supplemented with Chlorella vulgaris.

This study aimed to evaluate the effects of dietary Chlorella vulgaris (CV) on the distribution of immune cells, intestinal morphology, intestinal barrier function, antioxidant markers, and the cecal microbiome in 10-day-old broiler chickens. A total of 120 day-old Ross 308 male broiler chicks were assigned to two dietary treatments using a randomized complete block design, with body weight as the blocking factor. Birds fed a diet containing CV showed an increase in CD4+ T cells (p < 0.05) compared to those fed the control diet. The relative mRNA expression of intestinal epithelial barrier function-related markers (occludin and avian β-defensin 5) was elevated (p < 0.05) in the CV-supplemented group compared to the control group. The alpha diversity indices (Chao1 and observed features) of the cecal microbiome in 10-day-old birds increased (p < 0.05), indicating higher richness within the cecal bacterial community. In the microbiome analysis, enriched genera abundance of Clostridium ASF356 and Coriobacteriaceae CHKCI002 was observed in birds fed the diet containing CV compared to those fed the control diet. Taken together, dietary CV supplementation might alter intestinal barrier function, immunity, and microbiomes in 10-day-old broiler chickens.

Biological profile of the follicular fluid. A pilot study

BACKGROUND: One of the most important research areas in the field of reproductive medicine is the search for biochemical and immunological parameters of oocyte quality and predicting the effectiveness of assisted reproductive technology protocols.&#x0D; AIM: The aim of this study was to evaluate the expression of follicular fluid soluble human leukocyte antigen-G, human leukocyte antigen-E, human leukocyte antigen-C, progesterone-inducing blocking factor, and relaxin levels in women with reproductive disorders.&#x0D; MATERIALS AND METHODS: This prospective cohort study included 22 patients undergoing infertility treatment in a superovulation stimulation protocol using gonadotropin-releasing hormone antagonists. The inclusion criteria were age from 25 to 39 years, tubal-peritoneal factor infertility, and voluntary participation informed consent. The levels of soluble human leukocyte antigen-G, human leukocyte antigen-E, human leukocyte antigen-C, progesterone-inducing blocking factor, and relaxin in follicular fluid samples were determined on the day of transvaginal follicle puncture by enzyme immunoassay.&#x0D; RESULTS: We established an inverse correlation between the expression levels of progesterone-inducing blocking factor and relaxin (r = 0.450) in the follicular fluid, antibodies to thyroperoxidase (r = 0.649), and thyroid-stimulating hormone (r = 0.519). We also found a direct correlation between human leukocyte antigen-E parameters in the follicular fluid, age (r = 0.813) and Body Mass Index (r = 0.866), as well as between human leukocyte antigen-C expression levels and total testosterone (r = 0.960). No data were obtained on any significant correlations between the studied biomarkers and the number of received oocytes.&#x0D; CONCLUSIONS: In this comprehensive study, we were the first who found the expression levels of five different follicular fluid components, namely, soluble human leukocyte antigen-G, human leukocyte antigen-E, human leukocyte antigen-C, progesterone-inducing blocking factor, and relaxin. Such a complex assessment of the follicular fluid can allow for establishing the quality of the oocyte to predict the onset of pregnancy in an in vitro fertilization protocol.

Aberrations in the progesterone pathway and the Th1/Th2 cytokine dichotomy - An evaluation of RPL predisposition in the northeast Indian population.

Recurrent pregnancy loss (RPL) is the spontaneous loss of two or more consecutive pregnancies prior to 20weeks of gestation, occurring in 1% of the reproductive-age population. It is a major cause of infertility in India with a staggering 7.46% prevalence rate. Blood and product of conception (POCs) from RPL cases (n=65) were enrolled for this study, along with cases of medically terminated pregnancy (MTP, n=80) and term delivery cases (n=90) as control. ELISA for progesterone and progesterone induced blocking factor (PIBF) levels was carried out, followed by mRNA expression analysis of progesterone receptor isoform B (PR-B) and its downstream immunomodulatory effectors, namely, PIBF, IL-10 and IL-12. Screening of PROGINS haplotype of PR gene and PIBF polymorphism were also conducted to correlate with their respective gene expression profiles. Serum progesterone level was found to be comparable in the RPL and MTP cases. Although the mRNA expression of PR-B was found to be downregulated in the RPL cases, no significant PROGINS haplotype was observed. Presence of a single nucleotide polymorphism (SNP) in the PIBF gene (rs1372000) was more in healthy controls compared to RPL cases. Serum PIBF levels were found to be lower in the RPL cases with a resultant increase in IL-12 and a decrease in IL-10 mRNA expression in these cases. This study indicates that progesterone, acting through PIBF, modulates the immunological state of pregnancy to be Th1-biased in RPL, indicative of a pro-inflammatory, labour-like state not desired for a healthy pregnancy.

The Many Deaths of Supercapacitors: Degradation, Aging, and Performance Fading

AbstractHigh‐performance electrochemical applications have expedited the research in high‐power devices. As such, supercapacitors, including electrical double‐layer capacitors (EDLCs) and pseudocapacitors, have gained significant attention due to their high power density, long cycle life, and fast charging capabilities. Yet, no device lasts forever. It is essential to understand the mechanisms behind performance degradation and aging so that these bottlenecks can be addressed and tailored solutions can be developed. Herein, the factors contributing to the aging and degradation of supercapacitors, including electrode materials, electrolytes, and other aspects of the system, such as pore blocking, electrode compositions, functional groups, and corrosion of current collectors are examined. The monitoring and characterizing of the performance degradation of supercapacitors, including electrochemical methods, in situ, and ex situ techniques are explored. In addition, the degradation mechanisms of different types of electrolytes and electrode materials and the effects of aging from an industrial application standpoint are analyzed. Next, how electrode degradations and electrolyte decompositions can lead to failure, and pore blocking, electrode composition, and other factors that affect the device's lifespan are examined. Finally, the future directions and challenges for reducing supercapacitors' performance degradation, including developing new materials and methods for characterizing and monitoring the devices are summarized.

Production of Superworm Larvae (Zophobas Morio Fabricius, 1776) with Azolla and Soft Pollard as Substrate: It’s Effect as Substitute to Protein Source on the Growth Performance, Carcass Yield, and Economics of Broiler Chicken

The study was conducted to assess the potential of superworm larvae Zophobas morio as protein source in broiler chicken ration. A total of 50 grams of larvae was cultivated in a controlled environment and then allocated into uniformly-sized boxes, following a completely randomized design (CRD) with 12 replications per treatment involving combined substrates: A) azolla-soft pollard, B) azolla-rice bran D2, and C) azolla-ground yellow corn. The larvae produced using azolla-soft pollard substrate were used as the protein ingredient in the subsequent experiment. The selection of the larvae was based on the highest yield and lowest neutral detergent fiber value. One hundred twenty-eight (128) day-old broiler chicks were distributed to the 4 dietary treatments in randomized complete block design with cage location as the blocking factor. Ration were formulated to contain 0%, 2%, 4%, and 6% superworm larvae meal (SLM) as protein ingredient. The experimental design used was Randomized Complete Block Design (RCBD) and data gathered were analyzed using one-way analysis of variance of SAS university edition. Broilers under control group exhibited better growth performance compared to those with SLM inclusion. However, gradual improvement in growth performance and economic analysis for birds fed at 6% SLM inclusion was observed. Moreover, increase in carcass and gizzard weight was also observed when SLM was included at 4% and 6% in the diet. Incorporating 6% superworm larvae meal (SLM) into the diets of broiler chickens can lead to a gradual enhancement in their growth performance. To minimize chitin content, it is recommended to harvest superworms at a lower instar stage.

PIBF1 regulates multiple gene expression via impeding long-range chromatin interaction to drive the malignant transformation of HPV16 integration epithelial cells

IntroductionHuman papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. ObjectivesWe established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. MethodsWe designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. ResultsWe successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. ConclusionWe highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

Growth performance, nutrient digestibility, intestinal morphology, cecal mucosal cytokines and serum antioxidant responses of broiler chickens to dietary enzymatically treated yeast and coccidia challenge

BackgroundThere is a growing search for natural feed additives to alleviate the deleterious effects of coccidia infection in poultry production. This study aimed to investigate the effect of enzymatically treated yeast (ETY) on the growth performance, nutrient digestibility, intestinal morphology, antioxidative status, and cecal mucosa cytokines of coccidia-challenged broiler chickens.MethodsFrom d 1 to 14 post hatching, 480 broiler chickens were allocated to 3 corn-soybean meal-based experimental diets with increasing concentrations of ETY (0, 1, or 2 g/kg). The experiment was designed as a randomized complete block design with body weight (BW) used as a blocking factor. On d 14 post hatching, the birds were re-randomized within each of the 3 experimental diets. Each of the 3 diet groups was split into a challenge or no-challenge group. This resulted in a 3 × 2 factorial arrangement of treatments. The coccidia challenge was administered on d 15 by an oral gavage.ResultsDietary ETY improved (P < 0.05) the G:F of birds on d 21 regardless of the challenge state and linearly increased (P < 0.01) the apparent ileal digestibility of dry matter (DM), nitrogen, and gross energy (GE). The coccidia challenge decreased (P < 0.05) BW gain and feed intake of broiler chickens and reduced (P < 0.01) the total tract retention of DM, GE, and nitrogen. The coccidia challenge increased (P < 0.01) the mRNA gene expression of TNFα, IL-1β, IL-10, and IL-6 in the cecal mucosa. There was a tendency (P = 0.08) for ETY to linearly reduce IL-1β expression. Additionally, ETY supplementation increased (P < 0.05) the gene expression of OCLN. Serum catalase increased (P < 0.05) with dietary ETY in broiler chickens on d 21. Dietary ETY linearly increased (P < 0.05) the ileal villus height to crypt depth ratio, and ileal goblet cell density in broiler chickens. The ileal and excreta oocyst counts decreased (P < 0.01) with increasing supplementation of dietary ETY in coccidia-challenged broiler chickens on d 21.ConclusionsDietary ETY enhanced nutrient utilization and augmented intestinal development in broiler chickens. However, dietary ETY did not completely attenuate the adverse effects of a coccidia challenge in broiler chickens.

Abstract 3065: Increased longevity and quality of life with treatment with a progesterone receptor modulator in a patient with treatment resistant stage IV small cell lung cancer

Abstract The progesterone receptor modulator, mifepristone, has been found to provide extension of life by years and marked palliative benefits in several cases of non-small cell lung cancer (NSCLC) despite progression with platinum-based chemotherapy, check-point inhibitors, and third-generation tyrosine inhibitors. Presented here is a case of small cell lung cancer (SCLC) treated with mifepristone. This patient was diagnosed at age 58 with stage IV NSCLC with EGFR deletion 19 mutation. He was treated with single agent osimertinib 80mg once/day. Two months later his serial CT scan showed improvement. He was treated with stereotactic ablative radiotherapy for one persisting lesion. He was able to conduct a very active life. However, clinical symptoms started to return after 8 months, and CT of the chest showed slightly increased size of a the previously treated right upper lobe mass with increased small right effusion, increased pleural nodularity, and new interlobular septal thickening. Biopsy of the pleural mass showed transformation to SCLC. He failed a clinical trial. He began mifepristone orally 200mg/day. Within 1 month he was able to resume normal activity including strenuous sports. CT scans 2 months later showed no longer any pleural effusions, pleural nodularity, or growth of the persisting nodule that had been previously radiated. His absence of clinical symptoms continued for 10 more months but CT now showed slight growth of the persisting lesion. He assumed that with the growth that mifepristone was losing its effectiveness, and after consultation with another oncologist, elected to be treated in another clinical study for a new promising drug for SCLC that precluded him from continuing mifepristone. He died 5 months later. The main benefit of mifepristone is believed to be by blocking membrane rather than nuclear progesterone receptors (PRs) that are responsible for producing an immunosuppressive protein called the progesterone induced blocking factor which allows various cancers to spread. A previous case of stage IV NSCLC without any tumor markers treated with mifepristone had no growth and good health x 2 ½ years when 1 lesion begins to grow slowly. His oncologist suggested stopping mifepristone and try a check-point inhibitor. Instead, he continued mifepristone. He died 3 years later from pneumonia still feeling quite well while the one lesion continued to grow slowly. Another case of rapidly progressing lung cancer diagnosed by CT scan corrected her severe hypoxia (PO2 70 mmHg) and hyponatremia (serum Na+ of 118 mmol/L) after 1 month of taking mifepristone. Her lesions mostly disappeared and 5 years later she died of a myocardial infarction. Though clinically suspicious of SCLC, it was not biopsy proven. Hopefully this case will inspire a clinical trial of PR antagonists for SCLC. Citation Format: Jerome H. Check, Carrie Wilson, Diane Check, Trina Poretta, Maya Srivastava. Increased longevity and quality of life with treatment with a progesterone receptor modulator in a patient with treatment resistant stage IV small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3065.

Feed particle size and amylase supplementation in diets for nursery piglets: Digestibility and growth performance

The objective of this study was to evaluate the effect of diet particle size, amylase supplementation, and their possible interaction on nutrient digestibility and performance of nursery pigs. A total of 352 whole male piglets (28-d-old) were distributed in a completely randomized block design with a 2 × 2 factorial scheme: 2 feed particle sizes; with or without inclusion of 80 kg-novo units (KNU) of amylase/kg. Initial weight was the blocking factor. The diets were pelleted, based on corn and soybean meal, and divided into pre-starter (28 to 42 d) and starter (43 to 63 d). The tested particle sizes were 339/588 µm and 696/920 µm for pre-starter and starter phases, respectively, and were obtained through grinding of the corn. Diets were fed ad libitum. Average daily feed intake (ADFI), average daily weight gain (ADWG), and feed conversion ratio (FCR) were evaluated. Apparent digestibility of dry matter (DM), crude protein (CP), and ether extract (EE), as well as digestible energy (DE) were additionally evaluated in the starter phase. No interaction between factors was observed throughout the experiment. In the pre-starter phase, piglets fed finer diets (339 µm) had lower FCR (P < 0.05), although ADFI and ADWG were not affected. In the starter phase, the use of a coarser diet (920 µm) led to greater ADFI and ADWG (P < 0.05), but with no effect on FCR, similarly to what was observed in the total period (28 to 63 days). Reducing the particle size increased EE digestibility (P < 0.05) but had no influence on DM and CP digestibility nor DE. Amylase supplementation increased ADFI and ADWG and reduced FCR in the pre-starter phase and total period (P < 0.05), and led to greater digestibility of DM, CP, and EE, as well as DE (P < 0.05). As a conclusion, fine grinding of diets can be applied to reduce FCR and increase fat digestibility in younger nursery pigs (up to 42-d-old), but coarser diets should be used at an older age (post-42-d) to prevent losses in ADFI and ADWG. Supplementation of 80 KNU/kg of exogenous amylase is recommended through the nursery phase (28 to 63 d) to improve growth performance, nutrient digestibility, and DE, regardless of diet particle size.

Effect of photoperiod during incubation on embryonic temperature, hatch traits, and performance of 2 commercial broiler strains

Provision of light during incubation has shown the potential to enhance hatching traits and affect posthatch productivity, physiology, and behavior. In this study, 2 repeated trials were conducted to investigate the effect of photoperiod and strain on the embryo temperature, hatching traits and posthatch growth performance of 2 commercial strains of broilers (Ross 308 and Cobb 500). In each trial, hatching eggs were randomly distributed into 6 incubators with 3 photoperiod treatments: blue LED light for 12 h d-1 (12L:12D) or 18 h d-1 (18L:6D) during entire incubation were compared with no illumination condition (DARK). Data were analyzed as a 3×2 factorial arrangement with the trial as the blocking factor. Embryos incubated under 12L:12D and 18L:6D had lower air cell temperature (P < 0.05) than the DARK embryos from d 13 of incubation onward except on the day of candling. The response of air cell temperature to periodic illumination differed between 2 strains. Cobb embryos had lower air cell temperature in 12L:12D than those incubated with 18L:6D from d 16 of incubation onward, whereas lower air cell temperature was found in Ross embryos when illuminated with 18L:6D photoperiod compared to those under 12L:12D. The 12L:12D treatment was associated with improved (P < 0.05) navel closure condition of hatchlings. There were no differences in hatchability, embryo mortality, body weight, or length at hatch among photoperiod groups or its combination with strain. No differences in production parameters were found between DARK and illuminated groups. However, 12L:12D had heavier (P < 0.05) body weight on d 14 of age and higher (P < 0.05) body weight gain than 18L:6D from d 7 to 14 of age. The results of this study indicate that providing blue LED light up to 18 h d-1 has no detrimental effect on production of broilers, however, 12L:12D light regime improved chick quality at hatch compared to DARK and resulted in heavier birds by d 14 compared to 18L:6D.

Lung Cancer - Standard Therapy and the Use of a Novel, Highly Effective, Well Tolerated, Treatment With Progesterone Receptor Modulators.

The most recent successful advances in lung cancer therapy have directly and increasingly focused on personalized tumor genetic/epigenetic/immunologic profiling, and the identification and development of novel pharmacologic agents aimed at those mutations [e.g., epidermal growth factor receptor (EGFR), Kristen rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK) and immunotherapy against programmed cell death protein 1 (PD-1) and its ligands] which have extended life and provided palliation for lung cancer-patients positive for these mutations. The objective of this study is to provide a review of the large number of drugs and their efficacy as of 2022, for lung cancer, but also introduce a novel treatment that has the potential, based on one controlled murine lung cancer study and 5 anecdotal human cases, that showed marked palliative and longevity benefits in very advanced lung cancer with no other treatment options, i.e., progesterone receptor (PR) antagonists targeting the immunosuppressive protein, the progesterone induced blocking factor (PIBF). Credibility, however, will only be provided when the efficacy can be demonstrated in a large series of lung cancer cases ideally with certain controls. Thus, the ultimate objective of the review is to interest oncologists with a large population of lung cancer patients to perform a well powered study to corroborate or refute the limited experience to date with PR antagonist therapy.

Energy and phosphorus utilization of pulses fed to broiler chickens

Energy and P utilization in faba beans and peas were evaluated in 3 broiler chicken experiments. In Exp. 1, 240 birds were allotted to 5 diets in a randomized complete block design with BW as a blocking factor on d 18 post hatching to determine the regression-derived energy utilization of faba beans (FB) and field peas (FP). In each of the respective Exp. 2 and 3, regression-derived P utilization in FB and FP were determined with 162 birds assigned to each of 3 diets in a randomized complete block design with BW as a blocking factor on d 19 post hatching. There were 8 replicate cages with 6 birds per cage in Exp. 1, and 6 replicate cages with 9 birds per cage in Exp. 2 and 3. The test ingredients were added to a corn-soybean meal-based diet at 15% or 30% in Exp. 1, whereas FB was included at 21%, 42%, or 63% and FP at 16%, 32%, or 48% in Exp. 2 and 3, respectively. In Exp. 1, the apparent ileal digestibility (AID) of gross energy (GE) and the ileal digestible energy (IDE) in the diets decreased linearly (P < 0.01). There was a quadratic response or a linear decrease (P < 0.05) with increasing concentrations of FB or FP, respectively, on the apparent total tract utilization (ATTU) of GE, metabolizable energy (ME), and nitrogen-corrected ME (MEn). The respective IDE, ME, and MEn determined were 2,541, 2,628, and 2,394 kcal/kg DM in FB and 2,254, 2,540, and 2,331 kcal/kg DM in FP. In Exp. 2 and 3, the ileal digestible and retainable P intake were linearly increased (P < 0.01). The estimated true ileal digestibility and true total tract utilization of P in FB were 66.5% and 66.7%, respectively. The respective corresponding values for FP were 73.4% and 73.8%. In conclusion, the information on utilization of energy and P in FB and FP provided could enhance proper diet formulation when using these ingredients.

Grain shear stress and bed-load transport in open channel flow with emergent vegetation

The prediction of bedload transport capacity in riverbed with aquatic vegetation is a pressing need for river restoration. Laboratory experiments were conducted to investigate the weak bed-load transport rates with emergent vegetation for different energy slopes and vegetation densities. Such rate was observed to increase as the energy slope increased and the vegetation density decreased. The bed shear stress calculated by subtracting the vegetation drag from the total flow driving force was unable to predict the measured bed-load transport rate. On the other side, the estimation of the grain shear stress using the Einstein partitioning method considering the form drag provided a reasonable prediction. On the basis of these results, an explicit formulation for estimating grain shear stress was developed to predict the bed-load transport rate in a vegetated channel by considering the superimposition of forces. In addition, a simple relationship between grain shear stress and total shear stress was established by the boundary layer model. It was inferred that bed-load transport rate decreases with the increase of vegetation blocking factor while the total shear stress remains constant. Comparatively, the proposed models were more accurate than literature models, improving the understanding of the bed-load transport in a vegetated flow.

Palatability of the Feeds Developed from Senegalia Mellifera Encroacher Bush when Fed to Weaned Damara Sheep

Feeds produced from Senegalia mellifera species have not been considered as an alternative feed to livestock during the dry season when rangelands cannot provide quality grazing resources. This study assessed the palatability of feeds developed from Senegalia mellifera when fed to weaned Damara sheep. A Randomized Complete Block Design with sex as the blocking factor was used for the palatability trial with four diets which were randomly allocated to growing sheep. Sixteen male and female weaned Damara sheep of four to five months of age were confined in individual pens of 2.5m x 3m. The trial consisted of a 5-day adaptation period followed by a 12-day trial period. Formulated diets differed (P 0.05) in their DM, OM, EE, NDF, ADF, and ash. The control diet had a higher (P 0.05) NDF concentration compared to diets with 4% urea or 4% NaOH. Feed intake was influenced (P 0.05) by the day and diet x day interactions. Urea (8%) and NaOH (4%) treatments improved the chemical composition and palatability for S. mellifera feed, but the reaction conditions, including chemicals, concentration, moisture content, pH, and duration, need to be optimized to allow greater reduction of the lignin concentration.

Amino acid digestibility and net energy concentration in soybean meal for broiler chickens

The objective of this study was to determine coefficient of standardized ileal digestibility (CSID) of amino acids and net energy (NE) concentration of soybean meal (SBM) in broiler chickens. Six SBM originating from different regions in the United States were used in the current study. In experiment (Exp.) 1, a total of 576 birds on d 16 post hatching were allotted to 7 diets consisting of 6 diets containing 440 g/kg of each SBM as the sole source of nitrogen and a nitrogen-free diet. Birds were fed from d 16 to 21 and euthanized for the ileal digesta collection on d 21 post hatching. In Exp. 2, birds were fasted for 12 h on d 17 post hatching. On d 18, birds were divided into an initial (8 birds) and final group (64 birds), and the initial group was euthanized and immediately frozen. The remaining 64 birds were assigned to a basal diet or test diet replacing the basal diet with 200 g/kg of SBM. Experiment 2 lasted 7 d and excreta collection was conducted during the last 3 d. On d 25, birds were euthanized after a 12-h fast, individually weighed, and immediately frozen. The whole frozen intact bird carcass was ground and analyzed for gross energy. Energy retention was estimated as a difference in total body energy between the initial and final groups. In both experiments, the experimental design was a randomized complete block design with body weight as a blocking factor. In Exp. 1, the CSID of several indispensable amino acids in SBM1 was greater (P < 0.05) compared with SBM2, SBM3, and SBM6. In Exp. 2, energy retention was greater (P < 0.05) in the basal diet group, whereas NE for maintenance was lower compared with the test diet group (P < 0.05) resulting in a tendency for greater NE intake in the basal diet group (P = 0.084). Values for metabolizable energy (ME), nitrogen-corrected ME, and apparent total tract utilization of gross energy and nitrogen were greater (P < 0.05) in the basal diet group, however, a statistical difference in NE and dietary NE to ME ratio between the basal and test diets was not observed. In conclusion, different values for CSID of amino acids should be applied when formulating broiler diets containing SBM; furthermore, ME, NE, and NE to ME ratio in SBM were 12.61 MJ/kg dry matter, 8.58 MJ/kg dry matter, and 0.682, respectively.

Comparison of standardized ileal digestibility of amino acids in faba beans and field peas in broiler chickens and pigs.

An experiment, using the same set of five diets was conducted to determine and compare the standardized ileal digestibility (SID) of amino acids (AA) in faba beans and three cultivars of field peas in broiler chickens and pigs. Four test diets were prepared to contain faba beans, DS-Admiral field peas, Hampton field peas, or 4010 field peas as the sole source of nitrogen. A nitrogen-free diet (NFD), as the fifth diet, was prepared to estimate the basal endogenous losses of AA to determine the SID of AA in the test ingredients. A total of 416 male broiler chickens with an initial body weight (BW) of 951 ± 111 g were allotted to five diets in a randomized complete block design with BW as a blocking factor on day 21 posthatching. There were 8 replicate cages with 10 birds per cage for diets containing test ingredients and 12 birds per cage for NFD. All birds were allowed ad-libitum access to feed for 5 days. On day 26 posthatching, all birds were euthanized by CO2 asphyxiation and digesta contents were collected from the distal two-thirds of the ileum. Twenty barrows with an initial BW of 30.2 ± 1.58 kg, surgically fitted with T-cannulas in the distal ileum, were divided into four blocks according to BW and each block was assigned to a 5 × 2 incomplete Latin Square design that consisted of five dietary treatments and two experimental periods. For each experimental period, there was a 5-day adaptation period followed by a 2-day collection of ileal digesta samples. The data were analyzed as a 2 × 4 factorial treatment arrangement with the effect of species (i.e., broiler chickens and pigs) and test diets (i.e., four test ingredients). For broiler chickens, the SID of Lys in faba beans, DS-Admiral field peas, and Hampton field peas were above 90% but in 4010 field peas, it was 85.1%. The SID of Lys in faba beans, DS-Admiral field peas, and Hampton field peas for pigs was above 80% but was 78.9% in 4010 field peas. The respective SID of Met in faba beans, DS-Admiral field peas, Hampton field peas, and 4010 field peas were 84.1%, 87.3%, 89.8%, and 72.1% for broiler chickens, and 71.5%, 80.4%, 81.8%, and 68.1% for pigs. The SID of AA in 4010 field peas was the least (P < 0.05) for chickens, but in pigs, it was comparable with faba beans. In conclusion, the SID of AA in faba beans and field peas was greater in broiler chickens compared with pigs and there was a cultivar effect.

Performance response of increasing the standardized ileal digestible tryptophan:lysine ratio in diets containing 40% dried distiller grains with solubles.

A total of 1,170 pigs (PIC 800 × PIC, initially 38.6 kg) were used in a 98-d grow-finish study to determine the performance response of pigs fed increasing levels standardized ileal digestible (SID) Trp:Lys ratio in diets containing 40% dried distillers grains with solubles (DDGS). Five dietary treatments were fed and consisted of a corn-soybean meal (SBM) diet or diets containing 40% DDGS with SID Trp:Lys ratios of 15%, 18%, 21%, or 24%. Each treatment was replicated 9 times and pens contained 26 pigs with the equal number of gilts and barrows. Data was analyzed as a randomized complete block design with previous nursery treatment as a random blocking factor. Pair-wise comparisons were used to evaluate the impact of diets on performance and carcass traits; specifically to compare the corn-SBM dietary treatment against other dietary treatments. Single degree of freedom orthogonal polynomials were used to evaluate the dose-response of increasing the SID Trp:Lys ratio in 40% DDGS diets. Increasing the SID Trp:Lys ratio in diets containing 40% DDGS increased (linear, P ≤ 0.02) average daily gain (ADG), average daily feed intake (ADFI), final body weight (BW), hot carcass weight (HCW), carcass gain, and daily carcass gain. Increasing the SID Trp:Lys ratio in 40% DDGS diets did not impact (P ≥ 0.65) gain to feed (G:F) for the cumulative period. Pigs fed the corn-SBM diet had greater (P ≤ 0.01) ADG and a heavier (P ≤ 0.01) final BW compared to pigs fed 40% DDGS diets, regardless of the SID Trp:Lys ratio. Diets that contained 40% DDGS with a SID Trp:Lys ratio of 24% had no difference (P|t| = 0.25) in ADFI compared to the corn-SBM dietary treatment. The cumulative G:F of pigs did not differ (P = 0.32) between pigs fed corn-SBM diets and diets containing 40% DDGS regardless of the SID Trp:Lys ratio. However, pigs receiving the corn-SBM diets had heavier HCW, greater carcass yields, total carcass gain, and daily carcass gain (P < 0.01) compared to pigs fed the 40% DDGS diets regardless of SID Trp:Lys ratio. In conclusion, increasing the SID Trp:Lys ratio in 40% DDGS diets improved ADG and ADFI for the overall grow-finish period. However, when compared to a corn-SBM diet, increasing the SID Trp:Lys ratio in 40% DDGS diets did not correct the growth performance or carcass characteristics of pigs.

The role of progesterone and the progesterone receptor in cancer: progress in the last 5 years

ABSTRACT Introduction Patients with various advanced cancers devoid of nuclear progesterone receptors (nPR) have demonstrated increased quality and length of life when treated with the PR modulator mifepristone, which likely works by interacting with membrane PRs (mPR). Areas covered Two immunomodulatory proteins are discussed that seem to play a role in cancers that proliferate whether the malignant tumor is positive or negative for the nPR. These two proteins are the progesterone receptor membrane component-1 (PGRMC-1) and the progesterone-induced blocking factor (PIBF). Both PGRMC-1 and the parent form of PIBF foster increased tumor aggressiveness, whereas splice variants of the 90 kDa form of PIBF inhibit immune response against cancer cells. Expert opinion The marked clinical improvement following 200–300 mg of mifepristone is likely related to blocking PIBF. In the low dosage used, mifepristone likely acts as an agonist for PGRMC-1 protein. Mifepristone may be less effective for cancers positive for the nPR because the nPR may be protective and blocking it may have detrimental effects. Based on this hypothetical model, the development of other potential treatment options to provide even greater efficacy for treating cancer are discussed.

Имплантационная несостоятельность эндометрия в циклах экстракорпорального оплодотворения у пациенток с хроническим эндометритом

Introduction. Chronic endometritis is one of the most frequent gynecological diseases which negatively impacts the main pathogenetic links in the morphogenesis of secretory and gestational endometrial transformation. These links determine implantation failure. The study aimed to verify the expression of estrogen receptors (ER) and progesterone receptors (PR), progesterone-induced blocking factor (PIBF) and stromal cell-derived factor-1 (SDF-1) in the endometrium of patients having chronic endometritis with ineffective IVF cycles or undeveloped pregnancies occurred after assisted reproductive technologies in their histories. Materials and methods. We formed 3 study groups: group I included samples of the endometrium of patients with ineffective IVF cycles (n=50); group II contained samples received from patients with a history of undeveloped pregnancy after IVF (n=50); and group III (the control group) included endometrial tissue from healthy patients (n=25). We carried out routine histological evaluation followed by an immunohistochemical assay with ER, PR, PIBF, and SDF-1 in the endometrial glands and stroma in the middle secretion phase. esults. The middle stage of the secretion phase of the menstrual cycle in endometrial samples of groups I and II was detected in only 46% and 42% of cases, respectively. We showed a decrease in the ER and PR expression in more than 92% of cases. Statistically significant decrease was detected in PIBF and SDF-1 expression in the endometrial glands and stroma within the implantation window in patients with a history of reproductive loss. Conclusion. Violation of implantation viability with an imbalance of chemokines, cytokines, cellular factors, and structural and functional characteristics of the endometrium was found in patients with revealed chronic endometritis and history of ineffective IVF cycles and miscarriage after ART. Keywords: endometrium,IVF, missed abortion after IVF, estrogen receptor, progesterone receptor, progesterone-induced blocking factor, stromal cell-derived factor-1

The sFlt-1/PlGF Ratio in Patients Affected by Gestational Diabetes and SARS-CoV-2 Infection.

Low values of the ratio of plasmatic soluble blocking factor FMS-like tyrosine Kinase 1 and placental growth factor (sFlt-1/PlGF) are required for an adequate placental angiogenesis and function. It has been shown that patients affected by gestational diabetes (GD) and patients with pneumonia from SARS-CoV-2 are characterized by an increased sFlt-1/PlGF ratio. The aim of the present study was to evaluate the sFlt-1-PlGF ratio in pregnancies complicated by COVID-19 and GD. We compared the plasmatic sFlt-1/PlGF ratio among the following groups of pregnant women: COVID-19, GD patients; COVID-19, non-GD patients; non-COVID-19, GD patients; and non-COVID-19, non-GD controls. We enrolled 62 women in the present study, who were divided as follows: 14 COVID-19, GD patients; 12 COVID-19, non-GD patients; 11 non-COVID-19, GD patients; and 25 non-COVID-19, non-GD controls. The COVID-19, GD patients presented a higher pre-pregnancy BMI, a higher prevalence of hypertensive disorders of pregnancy as a co-morbidity, and an increased need for medication for their diabetes. Neonatal data were similar between the groups. The controls showed a significantly lower sFlt-1/PlGF ratio compared to pregnancies complicated by GD and SARS-CoV-2 infection. The sFlt-1/PlGF ratio was higher in patients affected by both GD and SARS-CoV-2 infection; these subjects were characterized by a greater incidence of obesity and hypertensive disorders of pregnancy.