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1.
Chem Commun (Camb) ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686636

RESUMO

An AIE-based fluorescent probe was designed to evaluate peroxynitrite levels in complex biological samples. The newly synthesized hydrazone-conjugated probe fluoresces strongly in the presence of peroxynitrite. Clinically, the peroxynitrite levels can be measured in human serum and cellular mitochondria with an LOD of 6.5 nM by fluorescence imaging in vitro.

2.
Animals (Basel) ; 14(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38612355

RESUMO

The growth of the broiler industry has been accompanied with concerns over the environmental and social impacts on intensive production systems, as well as the welfare of the animals themselves. As a result, since the 2000s, there has been growing interest in alternative production systems that improve animal welfare and sustainability. In this context, it is important to prioritize the welfare of broilers in commercial production systems and to use reliable welfare indicators to provide consumers with information about the welfare of the animals they consume. Resource-based measures (RBM) are based on assessing the resources available to the birds in terms of their housing, environment, and management practices, such as stocking density, litter quality, lighting and air quality, etc. Outcome-based measures (OBM), also known as animal-based measures, focus on assessing the actual welfare outcomes for the birds, such as footpad dermatitis, hock burn, contamination or damage to feathers, gait score, mortality, etc. These OBM-based measures are one of the more direct indicators of welfare and can help identify any welfare issues. The present review highlighted the factors that affect animal welfare indicators focused on OBMs which can be used in the commercial broiler farms.

3.
Poult Sci ; 103(4): 103505, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359769

RESUMO

This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.


Assuntos
Lacticaseibacillus paracasei , Microbiota , Probióticos , Animais , Feminino , Antioxidantes , Galinhas , Dieta/veterinária , Probióticos/farmacologia , Probióticos/análise , Suplementos Nutricionais/análise , Ração Animal/análise
4.
Anim Biosci ; 37(3): 536-546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38186258

RESUMO

OBJECTIVE: This experiment was conducted to investigate the effect of grain-based pecking blocks on productivity and welfare status at two commercial broiler welfare-certified farms. METHODS: Production and welfare indicators were assessed at two farms (designated Farm A and B). Both farms had two windowless houses with forced tunnel-type ventilation and housed broilers at stocking densities of approximately 16.7 birds/m2 (Farm A) and 16.8 birds/m2 (Farm B). Each house was divided into two or three equal sections and was provided with or without pecking blocks. Grain-based pecking blocks, measuring 25 × 25 × 25 cm, were given to broilers in both farms at 1 block per 1,000 birds. Various parameters including productivity (body weight and flock uniformity), corticosterone levels (in fecal droppings and feathers), footpad dermatitis, hock burn, feather dirtiness, gait score, litter quality, body surface temperature, and volatile fatty acids in fecal samples were assessed at 26 days of age, whereas litter quality was analyzed at 13 and 26 days of age. RESULTS: There were no significant effects of providing pecking blocks on productivity (body weight and uniformity), fecal and feather corticosterone, welfare indicators (i.e., footpad dermatitis, hock burn, feather cleanliness, and gait score), and litter quality (i.e., moisture, nitrogen, and pH). No differences in body surface temperature between the control and enrichment treatments were noted in Farm B, but body surface temperatures of the head (p = 0.029) and legs (p = 0.011) in the enrichment vs. control group were elevated in Farm A. Butyrate concentration in the enrichment vs control group was higher in Farm B (p = 0.023), but this effect was not detected in Farm A. CONCLUSION: It is concluded that grain-based pecking blocks did not affect performance and welfare indicators. Further studies are warranted to elucidate the potential impact of grain-based pecking blocks on gut health indicators.

5.
Poult Sci ; 103(3): 103402, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266435

RESUMO

The present study was conducted to assess the animal welfare status of broiler chickens raised in conventional and welfare-certified farms. One conventional farm (30,000 birds/house, 1,488 m2/house, 2 houses) and one animal welfare-certified farm (32,000 birds/house, 1,920 m2/house, 2 houses) were selected to measure productivity, stress responses, and animal welfare indicators in 3 broiler flocks (2 farms/season, n = 6 flocks/farm type) during summer, autumn, and spring. Upon farm visits, body weight, uniformity, and animal welfare indicators (i.e., fecal and feather corticosterone, footpad dermatitis, hock burn, feather dirtiness, and gait score) were measured at 26 d posthatch. Also, moisture, nitrogen, and pH of litter, light intensity, ammonia concentration, and body surface temperature of head, chest, and legs were measured. There was no difference in body weight and uniformity between farm types. Fecal corticosterone concentrations were higher (P = 0.021) in welfare-certified vs. conventional farm, but no significant difference was found in feather corticosterone. Welfare-certified vs. conventional farm had lower percentages of hock burn (P = 0.018), feather dirtiness scores (P = 0.009), and gait score (P = 0.040), and there was no difference in footpad dermatitis. Nitrogen content in litter samples tended to be higher in conventional vs. welfare-certified farms (P = 0.094), and there was no difference in moisture and pH between farm types. Ammonia concentration within the broiler houses was not different between 2 farms. However, animal welfare farm was found to be brighter than conventional farm (P < 0.001). The body surface temperature of head, chest, and legs was not different between farm types. In conclusion, the welfare-certified farm had higher welfare measures, including lower hock burn, feather dirtiness, and gait score, confirming an overall improvement in welfare indicators. However, the observation on the elevated feather corticosterone noted in welfare vs. conventionally raised chickens warrants further studies.


Assuntos
Dermatite , Doenças das Aves Domésticas , Animais , Galinhas/fisiologia , Fazendas , Amônia , Corticosterona , Criação de Animais Domésticos , Bem-Estar do Animal , Peso Corporal , Dermatite/etiologia , Dermatite/veterinária , Nitrogênio
6.
Animals (Basel) ; 13(24)2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38136861

RESUMO

The present study investigated the effect of low temperature on laying performance, egg quality, body temperature, yolk malondialdehyde, yolk corticosterone, and serum biochemistry in laying hens. A total of 40 laying hens (Hy-Line Brown) aged 36 weeks were housed in one of two environmental chambers kept at 12 ± 4.5 °C (low temperature) or 24 ± 3 °C (normal temperature) for 4 weeks. Low vs. normal temperature significantly increased (p < 0.05) live body weight, feed intake, and feed conversion ratio in laying hens. Skin surface temperature, but not rectal temperature, was decreased in laying hens exposed to low vs. normal temperature. Hens exposed to low temperature laid an intense eggshell color compared with those raised in a normal temperature. Malondialdehyde concentrations in yolk were increased in low-temperature-exposed laying hens compared with those at normal temperature conditions, but this effect was only noted on day 7, post the low-temperature exposure (p = 0.04). Finally, low vs. normal temperature increased the concentrations of total cholesterol and triglyceride in serum. Collectively, this study indicates that exposure to low temperature in laying hens initially disrupted antioxidant system and altered lipid metabolism in laying hens without inducing stress responses.

7.
Inorg Chem ; 62(45): 18767-18778, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37905835

RESUMO

The remarkable impact of photoredox catalytic chemistries has sparked a wave of innovation, opening doors to novel biotechnologies in the realm of catalytic antitumor therapy. Yet, the quest for novel photoredox catalysts (PCs) suitable for living systems, or the enhancement of catalytic efficacy in existing biocompatible PC systems, persists as a formidable challenge. Within this context, we introduce a readily applicable metal modulation strategy that significantly augments photoredox catalysis within living cells, exemplified by a set of metalloporphyrin complexes termed M-TCPPs (M = Zn, Mn, Ni, Co, Cu). Among these complexes, Zn-TCPP emerges as an exceptional catalyst, displaying remarkable photocatalytic activity in the oxidation of nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), and specific amino acids. Notably, comprehensive investigations reveal that Zn-TCPP's superior catalytic prowess primarily arises from the establishment of an efficient oxidative cycle for PC, in contrast to previously reported PCs engaged in reductive cycles. Moreover, theoretical calculations illuminate that amplified intersystem crossing rates and geometry alterations in Zn-TCPP contribute to its heightened photocatalytic performance. In vitro studies demonstrated that Zn-TCPP exhibits therapeutic potential and is found to be effective for photocatalytic antitumor therapy in both glioblastoma G98T cells and 3D multicellular spheroids. This study underscores the transformative role of "metal modulation" in advancing high-performance PCs for catalytic antitumor therapy, marking a significant stride toward the realization of this innovative therapeutic approach.


Assuntos
Metaloporfirinas , Metais , Metais/química , Metaloporfirinas/farmacologia , Oxirredução , Catálise
8.
Poult Sci ; 102(8): 102798, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37354615

RESUMO

The objective of this study was to determine the effects of dietary crude protein (CP) levels on production performance, nitrogen balance, and odor emission of excreta in growing pullets and laying hens from 13 to 32 wk of age. Two hundred and forty pullets (Hy-Line Brown) were randomly assigned to 1 of 4 dietary groups with 10 replicates per group, and 6 birds per replicate. Experimental diets were formulated to contain 4 graded CP levels in the diets of pullets ranging from 180, 160, 140, and 120 g/kg of diet during 13 to 18 wk (phase 1) and in the diets of laying hens from 190, 170, 150, and 130 g/kg of diet during 19 to 32 wk (phase 2). The limiting amino acids including lysine, methionine, and threonine were supplemented to maintain constant equal amino acid concentrations in all experiment diets. In phase 1, decreasing dietary CP levels did not affect growth performance but increased (linear and quadratic effect, P < 0.05) the relative abdominal fat contents and triglyceride concentration in serum samples. High-density lipoprotein cholesterol in serum samples decreased as the CP levels decreased in the diets of pullets. Dietary CP levels quadratically increased (P < 0.05) the villus height and the villus height to crypt depth ratio but did not affect tibia traits and relative organ weights in pullets at 18 wk. Apparent digestibility of dry matter and ether extract increased with decreasing dietary CP levels in pullets. Graded CP levels linearly increased the digestibility of dry matter, CP, and ether extracts but lowered that of crude ash in laying hens. Nitrogen excretion was linearly decreased (P < 0.05) as the dietary CP levels decreased in both pullets and laying hens. Dietary CP levels only affected carbon dioxide emission in pullets. In phase 2, dietary CP levels did not affect growth performance and the ages at first egg laying and to reach 50% egg production in laying hens. However, egg weights were decreased (linear and quadratic effect, P < 0.05) as the dietary CP level decreased in laying hens. Increasing dietary CP levels increased Haugh unit at 26 wk but lowered corticosterone concentrations in yolk samples at 22 wk. Collectively, this study shows that dietary CP levels could be decreased to reduce nitrogen excretion without adverse effects on performance and egg quality of growing pullets and laying hens.


Assuntos
Galinhas , Nitrogênio , Animais , Feminino , Odorantes , Suplementos Nutricionais/análise , Dieta/veterinária , Proteínas Alimentares , Aminoácidos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal
9.
Animals (Basel) ; 13(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37238018

RESUMO

A feeding trial was conducted to investigate the effect of dietary supplementation of Chlorella vulgaris (CV) or Tetradesmus obliquus (TO) on laying performance, egg quality, and gut health indicators of laying hens. A total of 144 Hy-Line Brown laying hens aged 21 weeks were randomly assigned to one of three dietary treatments with eight replicates of six hens. Dietary treatments were as follows: CON, basal diet; CV, basal diet + 5 g C. vulgaris/kg of diet; TO, basal diet + 5 g T. obliquus/kg of diet. The results showed that diets supplemented with CV or TO had insignificant effects on laying performance, egg quality (i.e., Haugh unit and eggshell strength and thickness), jejunal histology, cecal short-chain fatty acids, and antioxidant/immune markers in ileal mucosa samples of laying hens. Compared with the control group, the egg yolk color score was higher (p < 0.05) in laying hens fed on diets containing CV and TO, although the former was a more intense yellow than the latter. Small intestinal lamina propria cells were isolated using flow cytometry to examine the percentages of immune cell subpopulations. Dietary microalgae did not affect B cells or monocytes/macrophages but altered the percentage of CD4+ T cells and CD8- TCR γδ T cells. Collectively, diets supplemented with C. vulgaris or T. obliquus can improve egg yolk color and would modulate host immune development and competence in laying hens.

10.
Int J Mol Sci ; 24(9)2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37175897

RESUMO

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10-60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G1-phase cells was observed with arrest at the G2 phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.


Assuntos
Cinnamomum zeylanicum , Neoplasias do Colo , Humanos , Cinnamomum zeylanicum/química , Apoptose , Neoplasias do Colo/tratamento farmacológico , Células HT29 , Morte Celular , Proliferação de Células , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Sobrevivência Celular
11.
Animals (Basel) ; 13(3)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36766239

RESUMO

Oxidative stress is defined as an imbalance between pro-oxidants and anti-oxidants within biological systems, leading to tissue damage and compromising the health of afflicted animals. The incorporation of dietary anti-oxidants into chicken diets has been a common practice to improve the performance, health, and welfare of the host by protecting against oxidative stress-induced damage. Methyl sulfonyl methane (MSM), a naturally occurring organosulfur compound found in various plant sources, has demonstrated various beneficial biological properties, including anti-inflammatory and anti-oxidant properties in both in vitro and in vivo studies. MSM has been utilized as a dietary supplement for humans for its anti-oxidant, analgesic, and anti-inflammatory properties. It has also been administered to domestic animals, including cattle, pigs, and chickens, owing to its recognized anti-oxidant effect. This review summarizes the biological and physiological functions of dietary MSM in poultry.

12.
Cell Death Dis ; 13(7): 655, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902580

RESUMO

X-linked inhibitor of apoptosis-associated factor-1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in many human cancers. Despite accumulating evidence for the pro-apoptotic role for XAF1 under various stressful conditions, its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 increases cell sensitivity to ER stress and acts as a molecular switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. Mechanistically, XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313 (ZNF313)-mediated destruction complex. Moreover, XAF1 expression is activated through PERK-Nrf2 signaling and destabilizes C-terminus of Hsc70-interacting protein (CHIP) ubiquitin E3 ligase, thereby blocking CHIP-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α) that is involved in in the adaptive ER stress response. In tumor xenograft assays, XAF1-/- tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.


Assuntos
Estresse do Retículo Endoplasmático , Neoplasias , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/metabolismo , Humanos , Neoplasias/patologia , Proteínas Serina-Treonina Quinases , Ubiquitina-Proteína Ligases/metabolismo , Resposta a Proteínas não Dobradas
13.
Gels ; 8(6)2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35735713

RESUMO

Emulsion gel has been used to replace animal fats in meat products. Konjac is a widely used gelling agent; however, its low emulsion stability limits its use in meat products. This study aimed to examine the quality characteristics of ß-cyclodextrin (CD)-supplemented konjac-based emulsion gel (KEG) (CD-KEG) and its application as a fat substitute in emulsion-type sausages. The supplementation of CD increased hydrogen bonds and hydrophobic interactions with konjac and oil in the gels, respectively. Additionally, CD increased the structural complexity and strength of KEG. Since adding more than 6% of CD to KEG did not increase the gel strength, 6% CD-added KEG was adopted to substitute for pork backfat in manufacturing low-fat emulsion-type sausages. The following formulations of the sausages were prepared: pork backfat 20% (PF20); pork backfat 10% + KEG 10% (KEG10); KEG 20% (KEG20); pork backfat 10% + CD-KEG 10% (CD-KEG10); CD-KEG 20% (CD-KEG20); and pork backfat 5% (PF5). The CD-KEG20 formulation exhibited higher viscosity and viscoelasticity than KEG20, which suggested that CD improves the rheological properties and the thermal stability of meat batter. Additionally, CD-KEG20 showed similar emulsion stability, cooking yield and texture parameters compared with PF20. Therefore, 6% CD-added KEG is a suitable fat substitute for preparing low-fat emulsion-type sausages.

14.
Animals (Basel) ; 12(9)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35565626

RESUMO

The objective of this study was to evaluate the effects of dietary sulfur from either organic (methyl sulfonyl methane, MSM) or inorganic (sodium sulfate, SS) sources on the growth performance of broiler chickens challenged against a high-dose coccidiosis vaccine. A total of 320 day-old Ross 308 broiler chicks were randomly placed into 32 pens of 10 birds each (keeping 16 pens/control group and 8 pens/treatment group until 21 days post-hatch) and reared for 28 days. The experimental diets were formulated by mixing a corn and soybean meal-based control diet with MSM or SS. At 21 days post-hatch, half (n = 8) of the control and all of the sulfur-added diet-fed (i.e., MSM and SS) groups were challenged with a 30-fold dose of a commercially available Eimeria vaccine (Livacox® T coccidiosis vaccine). Unchallenged control chicks (n = 8) were considered as the negative control group. At 21 days (before coccidiosis vaccine challenge), the production parameters and cecal short-chain fatty acids were not affected by dietary treatments. The concentrations of total antioxidant capacity in liver samples were elevated in both the MSM and SS groups compared with the control group (p = 0.001). During 21 to 28 days (i.e., one week post coccidiosis vaccine challenge), challenge tended to lower body weight and feed intake by an average of 5.3% (p = 0.262) and 2.8% (p = 0.504), respectively, but to increase the feed conversion ratio by an average of 2.7% (p = 0.087) compared with the non-challenged control groups. None of dietary sulfur groups affected the body weight gain, feed intake, or feed conversion ratio of vaccine-challenged chickens. Mild Eimeria-specific lesions were noted in duodenum (p = 0.006), jejunum (p = 0.017), and ceca (p = 0.047), but dietary sulfur treatments did not affect the Eimeria-induced gut lesion scores. At 28 days, Eimeria challenge significantly impaired (p = 0.001) the apparent ileal digestibility of crude protein and crude ash compared with the naïve control group. Dietary MSM increased the apparent ileal digestibility of crude ash by 15.5% on average compared with the coccidiosis vaccine control group. We conclude that dietary antioxidant sulfur of organic or inorganic origins at the inclusion level (i.e., 0.7 g sulfur/kg of diet) has a limited effect on the growth performance of chickens challenged with coccidiosis vaccine.

15.
Anim Biosci ; 35(10): 1566-1574, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35507865

RESUMO

OBJECTIVE: This study investigated the effects of dietary methyl sulfonyl methane (MSM) and selenium (Se) on the laying performance, egg quality, gut health indicators, egg yolk Se content, and antioxidant markers in laying hens. METHODS: One hundred ninety-two 73-wk-old laying hens were randomly divided into four groups with eight replicates of six hens each. Four diets were prepared in a 2×2 factorial arrangement with or without MSM and Se. The trial lasted for 12 wk. RESULTS: There were no interaction effects or main effects (p>0.05) on laying performance and egg quality. However, feed intake increased in Se-fed hens (p = 0.051) and decreased in MSM-fed hens (p = 0.067) compared with that of hens in the control group. Dietary MSM increased (p<0.05) the ileal villus height and villus height:crypt ratio in hens compared with those receiving the non-supplemented control diet. Dietary MSM and Se did not affect the percentage of short-chain fatty acids in the ileal contents. Dietary Se enriched the Se content in egg yolk compared with that of the non-supplemented control diet (p<0.05). Dietary Se increased (p<0.05) glutathione peroxidase levels in the liver and serum samples compared to the control diet. The total antioxidant capacity in the liver increased (p<0.05) in laying hens that were fed MSM-supplemented diets than in hens fed the control diet. Dietary MSM significantly increased the relative superoxide dismutase levels in serum samples (p<0.05). CONCLUSION: Supplementation with either MSM or Se independently improved the antioxidant capacity of laying hens. Furthermore, dietary Se produced Se-enriched eggs, but this effect was neither additive nor synergistic with dietary MSM.

16.
Oncogene ; 41(20): 2897-2908, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35430604

RESUMO

X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a pro-apoptotic tumor suppressor that is frequently inactivated in multiple human cancers. However, its candidacy as a suppressor in the pathogenesis of breast cancer remains undefined. Here, we report that XAF1 acts as a molecular switch in estrogen (E2)-mediated cell-fate decisions favoring apoptosis over cell proliferation. XAF1 promoter hypermethylation is observed predominantly in estrogen receptor α (ERα)-positive versus ERα-negative tumor cells and associated with attenuated apoptotic response to E2. XAF1 is activated by E2 through a G protein-coupled estrogen receptor-mediated non-genomic pathway and induces ERα degradation and apoptosis while it is repressed by ERα for E2 stimulation of cell proliferation. The XAF1-ERα mutual antagonism dictates the outcomes of E2 signaling and its alteration is linked to the development of E2-resistant tumors. Mechanistically, XAF1 destabilizes ERα through the assembly of breast cancer-associated gene 1 (BRCA1)-mediated destruction complex. XAF1 interacts with ERα and BRCA1 via the zinc finger (ZF) domains 5/6 and 4, respectively, and the mutants lacking either of these domains fail to drive ERα ubiquitination and apoptosis. E2-induced regression of XAF1+/+ tumors is abolished by XAF1 depletion while XAF1-/- tumors recover E2 response by XAF1 restoration. XAF1 and ERα expression show an inverse correlation in primary breast tumors, and XAF1 expression is associated with the overall survival of patients with ERα-positive but not ERα-negative cancer. Together, this study uncovers an important role for the XAF1-ERα antagonism as a linchpin to govern E2-mediated cell-fate decisions, illuminating the mechanistic consequence of XAF1 alteration in breast tumorigenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Neoplasias da Mama , Receptor alfa de Estrogênio , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Estradiol/farmacologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Feminino , Humanos
17.
Vet Sci ; 9(3)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35324847

RESUMO

The objectives of this study were to recover bacteriophages (BPs) from the intestinal digesta of BP-fed broilers and to evaluate the antibacterial effects of encapsulated or powdered BPs in broiler chickens challenged with Clostridium perfringens. Day-old broiler chicks (n = 320/experiment) were randomly assigned to 32 pens (n = 10 broilers/pen) and allocated to one of four dietary groups: (1) unchallenged group (NEG); (2) C. perfringens-challenged group (POS); (3) POS group fed a diet supplemented with powdered BPs; and (4) POS group fed a diet supplemented with encapsulated BPs. On days 21, 22, and 23 post-hatch, all chickens except NEG were orally inoculated twice a day with 2 mL C. perfringens (1.0 × 108 cfu/mL). Varying BP levels were detected in gut digesta at all ages and were numerically or significantly higher in the encapsulated BP group than in the powdered BP group. Dietary powder or encapsulated BPs reversed the C. perfringens-mediated increase in crypt depth. In addition, villus height to crypt depth ratio was elevated in the NEG and BP-treated/challenged groups compared with that in the POS group. C. perfringens counts in the cecum were significantly lower in the BP-fed chickens than in the POS group. The encapsulated BP-supplemented diet-fed chickens had the highest serum IgA levels. Collectively, our results suggest that dietary BP remains viable in intestinal digesta upon ingestion and can inhibit cecal C. perfringens counts.

18.
Neurooncol Adv ; 4(1): vdac013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35274103

RESUMO

Background: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a tumor suppressor that is commonly inactivated in multiple human cancers. However, its role in the pathogenesis and therapeutic response of glioma is poorly characterized. Methods: XAF1 activation by temozolomide (TMZ) and its effect on TMZ cytotoxicity were defined using luciferase reporter, flow cytometry, and immunofluorescence assays. Signaling mechanism was analyzed using genetic and pharmacologic experiments. In vivo studies were performed in mice to validate the role of XAF1 in TMZ therapy. Results: Epigenetic alteration of XAF1 is frequent in cell lines and primary tumors and contributes to cancer cell growth. XAF1 transcription is activated by TMZ via JNK-IRF-1 signaling to promote apoptosis while it is impaired by promoter hypermethylation. In tumor cells expressing high O 6-methylguanine-DNA methyltransferase (MGMT), XAF1 response to TMZ is debilitated. XAF1 facilitates TMZ-mediated autophagic flux to direct an apoptotic transition of protective autophagy. Mechanistically, XAF1 is translocated into the mitochondria to stimulate reactive oxygen species (ROS) production and ataxia telangiectasia mutated (ATM)-AMP-activated protein kinase (AMPK) signaling. A mutant XAF1 lacking the zinc finger 6 domain fails to localize in the mitochondria and activate ROS-ATM-AMPK signaling and autophagy-mediated apoptosis. XAF1-restored xenograft tumors display a reduced growth rate and enhanced therapeutic response to TMZ, which is accompanied with activation of ATM-AMPK signaling. XAF1 expression is associated with overall survival of TMZ treatment patients, particularly with low MGMT cancer. Conclusions: This study uncovers an important role for the XAF1-ATM-AMPK axis as a linchpin to govern glioma response to TMZ therapy.

19.
Antioxidants (Basel) ; 11(3)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35326167

RESUMO

This study evaluated the effects of graded levels of dietary methyl sulfonyl methane (MSM) on the laying performance, egg quality, antioxidant capacity, and the incorporation of MSM into the egg albumen of laying hens. A total of 240 73-week-old laying hens (Lohmann Brown Lite) were randomly allotted to 1 of 5 dietary treatments, with 8 replicates of 6 birds per replicate. The experimental diets were formulated by mixing corn and soybean meal-based diets with MSM to reach 0.0, 1.0, 2.0, 3.0, and 4.0 g per kg of diet, and were fed to the birds for 12 weeks. Increasing dietary MSM led to a significant quadratic effect on the feed intake and feed conversion ratio at 4 weeks (p < 0.05). However, none of the egg qualities and egg components were altered by dietary MSM. The deposition of MSM in egg albumens increased in a linear manner (p < 0.05) in response to the increasing dietary MSM levels. The concentration of malondialdehyde in the egg yolk decreased at 12 weeks (linear and quadratic effect; p < 0.05), as the dietary MSM levels increased. Increasing dietary MSM affected the indicators of antioxidant/oxidative stress in the serum samples, such as superoxide dismutase at 12 weeks (linear and quadratic effect; p < 0.05), total antioxidant capacity at 8 and 12 weeks (linear effect; p < 0.05), and malondialdehyde at 8 weeks (linear effect; p < 0.05). Taken together, our study shows that dietary MSM has potential to be used as an antioxidant feed additive for laying hens, and can be used to produce functional eggs with health benefits for humans.

20.
J Therm Biol ; 103: 103167, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35027187

RESUMO

The present study investigated the effects of relative humidity (RH) on the laying performance, egg quality, and stress indicators of laying hens raised at high ambient temperatures. A total of 180 Hy-Line Brown laying hens (68-wk-old) were randomly allotted to one of the following three RH conditions for 12 h a day (9:00 a.m.-9:00 p.m.) over four weeks: low RH (LRH; 25% RH), moderate RH (MRH; 50% RH), and high RH (HRH; 75% RH); ambient temperature was 30 °C under all treatments. None of the RH treatments affected hen-day egg production, egg weight, or egg mass (P > 0.05). However, feed intake was lower in the HRH group than in the LRH group (P < 0.05). Plasma corticosterone (CORT) concentration on day 21, yolk CORT concentration on day 3, and albumen CORT concentration on day 7 following RH exposure were higher in the HRH group than in the LRH group (P < 0.05). Moreover, plasma HDL-cholesterol concentration on day 14 was higher in the HRH group than in the LRH group (P < 0.05). On days 3 and 14, the Haugh unit decreased (P < 0.05) in the LRH group compared with that in the MRH and HRH groups. The HRH-exposed laying hens showed the lowest (P < 0.05) eggshell thickness on day 14. The absolute weights of eggshell, yolk, and albumen decreased in the HRH group compared with those in the MRH and LRH groups. Overall, high RH lowered feed intake and egg quality except for the Haugh unit, and induced stress response as manifested by elevated plasma, yolk, and albumen CORT concentrations. To our best knowledge, the present study is the first to demonstrate the role of RH in triggering temperature stress responses in laying hens.


Assuntos
Galinhas/fisiologia , Ovos/análise , Resposta ao Choque Térmico/fisiologia , Umidade , Ração Animal/análise , Animais , Corticosterona/sangue , Dieta/veterinária , Ingestão de Alimentos , Casca de Ovo/fisiologia , Feminino , Temperatura Alta
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