Colostrum-derived extracellular vesicles: potential multifunctional nanomedicine for alleviating mastitis.

Bovine mastitis is an infectious disease that causes substantial economic losses to the dairy industry worldwide. Current antibiotic therapy faces issues of antibiotic misuse and antimicrobial resistance, which has aroused concerns for both veterinary and human medicine. Thus, this study explored the potential of Colo EVs (bovine colostrum-derived extracellular vesicles) to address mastitis.

Nuclear factor erythroid 2-related factor 1 regulates the expression of proteasomal genes in ketotic cows and protects mammary cells against free fatty acid-induced endoplasmic reticulum stress.

Ketosis is a common metabolic disorder in high-yielding cows and is characterized by high concentrations of BHB and free fatty acids (FFA). High concentrations of FFA induce endoplasmic reticulum (ER) stress in multiple organs including mammary tissue, and result in reduced milk production and lower milk quality. In nonruminants, loss of nuclear factor erythroid 2-related factor 1 (NFE2L1) results in ER stress.

Epigallocatechin-3-gallate protects bovine ruminal epithelial cells against lipopolysaccharide-induced inflammatory damage by activating autophagy.

Background: Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown.

Narirutin activates TFEB (transcription factor EB) to protect against Acetaminophen-induced liver injury by targeting PPP3/calcineurin.

Acetaminophen (APAP) overdose is the predominant cause of drug-induced liver injury worldwide. The macroautophagy/autophagy-lysosomal pathway (ALP) is involved in the APAP hepatotoxicity. TFEB (transcription factor EB) promotes the expression of genes related to autophagy and lysosomal biogenesis, thus, pharmacological activation of TFEB-mediated ALP may be an effective therapeutic approach for treating APAP-induced liver injury.

Activated autophagy-lysosomal pathway in dairy cows with hyperketonemia is associated with lipolysis of adipose tissues.

Activated autophagy-lysosomal pathway (ALP) can degrade virtually all kinds of cellular components, including intracellular lipid droplets, especially during catabolic conditions. Sustained lipolysis and increased plasma fatty acids concentrations are characteristic of dairy cows with hyperketonemia. However, the status of ALP in adipose tissue during this physiological condition is not well known.

Impaired autophagy aggravates oxidative stress in mammary gland of dairy cows with clinical ketosis.

When ketosis occurs, supraphysiological levels of free fatty acids (FFA) can cause oxidative injury to the mammary gland and autophagy can regulate the cellular oxidative status. The aim of this study was to investigate the autophagy status of mammary tissue and its associations with oxidative stress in healthy and clinically ketotic dairy cows. Mammary tissue and blood samples were collected from healthy cows [n = 15, β-hydroxybutyrate (BHB) <0.

Overactivation of hepatic mechanistic target of rapamycin kinase complex 1 (mTORC1) is associated with low transcriptional activity of transcription factor EB and lysosomal dysfunction in dairy cows with clinical ketosis.

Ketosis occurs most frequently in the peripartal period and is associated with liver injury and steatosis. Lysosomes serve as the terminal degradative station and contribute to liver homeostasis through their role in the digestion of dysfunctional organelles and lipid droplets. Transcription factor EB (TFEB) has been identified as a master regulator of lysosomal function.

Free fatty acids impair autophagic activity and activate nuclear factor kappa B signaling and NLR family pyrin domain containing 3 inflammasome in calf hepatocytes.

Free fatty acids (FFA)-induced hepatic inflammation agravates liver injury and metabolic dysfunction in dairy cows with ketosis or fatty liver. Under stressful conditions, autophagy is generally considered as a cell protection mechanism, but whether the FFA-induced inflammatory and stress effect on hepatocytes involves an autophagy response is not well known. Thus, the objective of this study was to investigate the effects of FFA on autophagy and the role of autophagy in the activation of NF-κB (nuclear factor kappa B) signaling and NLRP3 (NLR family pyrin domain containing 3) inflammasome in calf hepatocytes.

Propionate alleviates palmitic acid-induced endoplasmic reticulum stress by enhancing autophagy in calf hepatic cells.

Negative energy balance-induced high blood concentrations of free fatty acids during the early postpartum period in dairy cows is a major cause of liver injury. Cows in severe negative energy balance often have suboptimal intakes of feed, which contributes to shortfalls in production of ruminal propionate and circulating glucose. Although increasing propionate production by the rumen through feed additives such as propylene glycol is effective in helping cows alleviate the shortfall in dietary energy supply, mechanisms whereby propionate affects liver function beyond gluconeogenesis are unknown.

Inhibition of cell death inducing DNA fragmentation factor-α-like effector c (CIDEC) by tumor necrosis factor-α induces lipolysis and inflammation in calf adipocytes.

Dairy cows with ketosis exhibit signs of pronounced adipose tissue lipolysis and systemic inflammation, both of which exacerbate this metabolic disorder. In nonruminants, CIDEC plays a pivotal role in the formation of large unilocular lipid droplets. The present study aimed to ascertain the role of CIDEC in the lipolytic and inflammatory response of white adipose tissue (WAT) in vivo and in vitro.

Hepatic autophagy and mitophagy status in dairy cows with subclinical and clinical ketosis.

Severe negative energy balance around parturition is an important contributor to ketosis, a metabolic disorder that occurs most frequently in the peripartal period. Autophagy and mitophagy are important processes responsible for breaking down useless or toxic cellular material, and in particular damaged mitochondria. However, the role of autophagy and mitophagy during the occurrence and development of ketosis is unclear.

Cyanidin-3-O-glucoside improves non-alcoholic fatty liver disease by promoting PINK1-mediated mitophagy in mice.

Background And Purpose: Identifying safe and effective compounds that target to mitophagy to eliminate impaired mitochondria may be an attractive therapeutic strategy for non-alcoholic fatty liver disease. Here, we investigated the effects of cyanidin-3-O-glucoside (C3G) on non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism.

Experimental Approach: Non-alcoholic fatty liver disease was induced by a high-fat diet for 16 weeks.

Short communication: Enhanced autophagy activity in liver tissue of dairy cows with mild fatty liver.

During the transition period, dairy cows are challenged by increased energy demands and decreased dry matter intake, which can induce a variety of metabolic disorders, especially fatty liver. Dairy cows suffering from mild or moderate fatty liver in this period show no distinct clinical symptoms, indicating the occurrence of adaptive processes. The process of autophagy (an adaptive response) leads to degradation of intracellular components to generate energy and maintains cellular homeostasis during negative nutrient status.

Ketotic cows display a different serum nonesterified fatty acid composition.

The experiments reported in this research communication aimed to compare the serum nonesterified fatty acid (NEFA) composition in ketotic cows and healthy cows during the perinatal period. NEFAs play significant roles in etiology and pathology of ketosis. We hypothesized that ketotic cows will display a different serum NEFA composition compared to healthy controls, and fatty acid related indicators for ketosis prediction can be screened.

Hepatic nuclear factor kappa B signaling pathway and NLR family pyrin domain containing 3 inflammasome is over-activated in ketotic dairy cows.

Ketosis is an important metabolic disease that can negatively affect the production efficiency of dairy cows. Earlier studies have revealed metabolic and inflammatory alterations in the blood associated with ketosis; however, a link between ketosis and hepatic inflammation has not been well documented. The objective of this study was to investigate whether the nuclear factor kappa B (NF-κB) signaling pathway and NLR family pyrin domain containing 3 (NLRP3) inflammasome were activated in the liver of ketotic cows.

Impaired hepatic autophagic activity in dairy cows with severe fatty liver is associated with inflammation and reduced liver function.

The ability of liver to respond to changes in nutrient availability is essential for the maintenance of metabolic homeostasis. Autophagy encompasses mechanisms of cell survival, including capturing, degrading, and recycling of intracellular proteins and organelles in lysosomes. During negative nutrient status, autophagy provides substrates to sustain cellular metabolism and hence, tissue function.

Adaptations of hepatic lipid metabolism and mitochondria in dairy cows with mild fatty liver.

The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. Fatty liver is one of the main health disorders after parturition. Therefore, to investigate changes in hepatic lipid metabolic status and mitochondria in dairy cows with mild fatty liver, liver and blood samples were collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15).

High concentrations of fatty acids and β-hydroxybutyrate impair the growth hormone-mediated hepatic JAK2-STAT5 pathway in clinically ketotic cows.

The hepatic growth hormone (GH)-insulin-like growth factor (IGF)-I axis is essential for regulating intrahepatic lipid metabolism. Ketotic cows are characterized by high blood concentrations of fatty acids and β-hydroxybutyrate (BHB), which display lipotoxicity. The aim of this study was to investigate changes in the hepatic GH-IGF-I axis in ketotic cows and to determine the effects of fatty acids and BHB on the GH-IGF-I axis in calf hepatocytes.

FGF-21: promising biomarker for detecting ketosis in dairy cows.

The objective of this study was to investigate the measurement of serum fibroblast growth factor-21 (FGF-21), a protein mainly synthesized by the liver, as a sensitive biomarker for diagnosis of ketosis in dairy cows. Ninety Holstein-Friesian dairy cows (60 healthy and 30 ketosis cases) were selected and divided into a Ketosis group (K), and a Control group (C). We measured serum FGF-21 and other biochemical parameters by commercial ELISA kits.

The relationship between Fibroblast Growth Factor-21 and characteristic parameters related to energy balance in dairy cows.

Background: Negative energy balance (NEB) is a common pathological foundation of ketosis and fatty liver. Liver and fat tissue are the major organs of lipid metabolism and take part in modulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB develop during perinatal period. Fibroblast growth factor-21 (FGF-21) is a recently discovered protein hormone that plays an important and specific regulating role in adipose lipid metabolism and liver gluconeogenesis for human and mouse.